it has now been discovered that hexahydroindenopyridine compounds having the structure i ( a ) shown below , preferably having the structure shown in i ( b ) below : wherein the hydrogen atoms at positions 4a , 5 and 9b have the relative stereochemistry shown ( hydrogens at positions 4a and 5 are trans , hydrogens at 4a and 9b are cis to one another ; formula i ( b )); or the relative stereochemistry at position 9b can be reversed so that hydrogens at positions 4a and 5 are trans , hydrogens at 4a and 9b are trans to one another ; or all three hydrogens can be cis to one another ; or wherein the dashed line between 4a and 5 indicates that the compound may also be the 4a , 5 - dehydro compound , thus having a double bond between carbons 4a and 5 and where r 1 is hydrogen or straight - chain or branched c 1 - 6 alkyl , preferably c 1 - 3 alkyl , or c 3 - c 8 cycloalkyl ; r 2 is hydrogen , straight - chain or branched c 1 - 6 alkyl , preferably c 1 - 3 alkyl ; r 3 and r 5 are independently hydrogen , halogen , so 3 h , straight - chain or branched c 1 - 6 alkyl , ch 2 oh , ch 2 ome , straight chain or branched c 1 - 6 alkoxy , carboxyl ( cooh ) or a group which can be converted under mammalian physiological conditions to a carboxyl group , carboxylic acid ester ( coor where r is c 1 - 10 alkyl , c 6 - 10 aryl , c 7 - 10 aralkyl ), hydroxymethyl ester ( ch 2 oc ( o )— r where r is as defined above ), conh 2 , conhr , conr 2 , ch 2 oconhr , cn , ch ═ nnnhconh 2 , and halogen ; and r 4 is hydrogen , halogen , r 3 si or cor are not only antispermatogenic and have activities as much as about 40 times the oral anti - spermatogenic activity of the best known compounds as reported in previous u . s . pat . no . 5 , 319 , 084 , but also act as a spermicide to kill motile sperm , and also act as an anti - fungal agent . within the context of the present invention , the term “ anti - spermatogenic ” relates to the ability to disrupt the production of sperm in the testes , while the term “ spermicide ” or “ spermicidal ” relates to the ability to kill motile sperm after their production and , more preferably , after ejaculation . the compounds of the present invention have the relative stereochemistry shown in structure ( i ). this invention includes both individual enantiomeric forms ( essentially optically pure ) as well as any mixtures of these forms , for example , a racemic mixture . pharmaceutically acceptable salts of the compounds having structure ( i ) shown above are also included within this invention . pharmaceutically acceptable salts include , but not are limited to salts of a basic functional group ( such as but not limited to an amine group ) with inorganic acids such as hydrochloride , hydroiodide , sulphate , phosphate , diphosphate , hydrobromide and nitrate or salts of the basic functional group with an organic acid such as acetate , malate , maleate , fumarate , tartrate , succinate , citrate , lactate , methanesulfonate , p - toluenesulfonate , palmoate , salicylate and stearate ; or salts of an acidic functional group with metal ions such as ( but not limited to ) na , k , ca or salts of an acidic functional group with the ammonium ion , or salts of an acidic functional group with organic ions such as ( but not limited to ) amines and tetrasubstituted ammonium ions . substituent r 1 is preferably a straight - chain alkyl ( n - alkyl ), iso - alkyl or cycloalkyl group , such as methyl , ethyl , n - propyl , iso - propyl , n - butyl , iso - butyl , n - pentyl , iso - pentyl , n - hexyl , iso - hexyl , cyclopropyl , cyclopentyl , cyclohexyl . most preferably , r 1 is ethyl . substituent r 2 is also preferably a straight - chain or iso - alkyl group as described for r 1 described above . substituent r 3 is preferably in the para or 4 position of the ring and is preferably a group selected from hydroxymethyl ( ch 2 oh ), formyl ( cho ), carboxyl ( cooh ), carboxylic acid ester ( coor where r is c 1 - 10 alkyl , c 6 - 10 aryl , c 7 - 10 aralkyl ), and hydroxymethyl ester ( ch 2 oc ( o )— r where r is as defined above ), conh 2 , conhr , conr 2 , ch 2 oconhr , cn , ch ═ nhnhconh 2 , and halogen . substituent r 4 is preferably halogen including i , br , cl and f . the potent activity of these compounds is surprising . the halogen may be a radioactive isotope , for example 123 i , 125 i , or 131 i . other radioactive isotopes , such as for example 11 c , tritium ( 3 h ) or 18 f , or radioactive isotopes of bromine and chlorine , may be substituted for the usual ( nonradioactive ) isotopes in the above compounds . compound 1 is a racemic mixture . the structure of compound 1 is shown in fig1 , compound 1 . hexahydroindenopyridines have three asymmetric centers which can be defined using known nomenclature . alternatively the relative stereochemistry can be defined by the cis - trans relationships of the hydrogen atoms bonded to the carbon system at positions 4a , 5 and 9b of the tricyclic ring system , leading to stereochemical assignments . following the cahn - ingold - prelog nomenclature , the stereochemistry and name of compound 1 is ( 4ars , 5sr , 9brs )- 2 - ethyl - 2 , 3 , 4 , 4a , 5 , 9b - hexahydro - 7 - methyl - 5 -( 4 - methylphenyl )- 1h - indeno [ 1 , 2 - c ] pyridine . compound 1 has a hydrophobic methyl substituent on the 5 - phenyl group corresponding to substituent r 3 in structure ( i ) shown above . the antispermatogenic activity of compound 1 resides essentially exclusively in the (+) isomer ( the optical rotation is dextrorotatory when measured under the conditions described in cook et al ., 1995 ), which is an effective antispermatogenic drug in mice . antispermatogenic activity of other compounds of this series also resides essentially exclusively in one optical isomer . the measured optical rotation of these compounds , however , may be either (+) or (−), depending on the substitution pattern and the conditions of measurement , as is known to those skilled in stereochemistry . on the other hand , the antifungal properties of the compounds of the present invention are not stereospecific , with both (+) and (−) isomers active , although their relative activities may differ . the spermicidal effects of the compounds of the present invention have been found in the antispermatogenic isomers and are believed to be present also in the other isomers . the very polar carboxyl group or groups which can be metabolized under mammalian physiological conditions to a carboxyl group may be present at any position , preferably the para - position , of the 5 - phenyl ring of the compounds of the invention with retention of spermicidal and / or antifungal activity . for example , compounds in which the para - position is substituted with hydroxymethyl ( ch 2 oh ), formyl ( cho ), carboxyl ( cooh ) and methoxycarbonyl ( c ( o ) och 3 ) groups retain potent activity . these compounds exhibit activity despite the presence of a polar substituent in the para - position of the 5 - phenyl ring . by “ metabolized under mammalian physiological conditions ” is meant a functional group r 3 which is converted to a carboxyl group when a compound having structure ( i ) is administered to a living mammal for which antispermatogenic treatment is desired . administration may be by any conventional means or route , including but not limited to , oral , interperitoneal , intraveneous , subcutaneous , intramuscular , inhalation , buccal and skin penetration . these same administration routes are available for spermicidal and / or antifungal treatments , along with topical administration . the conversion of the group r 3 to a carboxyl group is readily determined by monitoring metabolites of the compound having structure ( i ) in the blood or in the urine . the metabolites may be monitored using conventional analysis methods such as mass spectrometry ( ms ), gas chromatography ( gc ), etc . preferably , at least 50 %, more preferably at least 80 % and even more preferably 90 %, 95 % or 100 % of functional groups r 3 are metabolized to a carboxyl group upon administration to the mammal , although this is not necessary in order to obtain spermicidal and / or fungicidal properties . the percentage of conversion can be determined by quantitatively analyzing a blood or urine sample to determine the relative amounts of unconverted compounds containing functional group r 3 relative to compounds in which r 3 has been converted to a carboxyl group using one of the conventional analysis methods noted above . the antispermatogenic activity of compound 1 is observed after a single oral dose of 30 mg / kg to rats , drastically reducing the weights of the testes within 24 h . degenerative changes in the seminiferous tubules are observed . spermatids became pycnotic , occasionally forming multinucleated associations . sertoli cells appear to be cytologically normal . it appears that compound 1 targets spermatids or the sertoli cell associated with these spermatids because histologic changes are observed in these spermatids first . compound 1 causes some lethargy and sedation in mice at an oral dose of 30 mg / kg and extreme lethargy at the same dose given subcutaneously . lethargy and sedation are obviously undesirable side effects in contraceptive agents . in contrast to the lethargy and sedation observed with compound 1 , the compounds of the present invention produce minimal lethargy . the compounds of the present invention allow one to separate the antifertility activity from the sedative activity observed with compound 1 . the compounds of the invention are , therefore , effective antifertility drugs in which the undesired side - effects of sedation and lethargy are markedly diminished . the compounds of the invention were tested in mice for their effects on spermatogenesis three days after a single oral dose by the procedure described in cook et al ( 1995 ) below . compounds active in this test have been shown also to be anti - fertility compounds . compounds were screened for antispermatogenic activity by dosing male mice on day 1 with a gavage dose of control vehicle , positive control ( compound 1 ) or compound of the invention . at 72 h after dosing , animals were killed and the testes were excised , trimmed of fat , and weighed . one testis was examined histologically and rated for spermatogenic potential using the spermatogenic index ( j . m . whitsett , p . f . noden , j . cherry and a . d . lawton , j . reprod . fertil ., 72 , 277 ( 1984 ), which is a semiquantitative estimate of the sperm producing ability of the testes the index is based on histological appearance of the spermatogenic cells in the seminiferous tubules . a scale of 1 to 6 is used with 5 to 6 being the normal status . a second assessment was based on the weight of the testes . tables 1 and 2 show pertinent biological results in terms of the change in testes weight ( tw ) and spermatogenic index ( si ) relative to a control containing only the administration vehicle , but no indenopyridine . in tables 1 and 2 , r 3 and r 4 refer to structures ib , where r 3 is in the para position ; r 1 is ethyl ; r 2 is methyl ; and r 5 is hydrogen . with an 8 - iodo - 7 - methyl - 4 ′- carboxy or 4 ′- carbomethoxy substituent pattern , an oral dose of 2 μmol / kg ( 1 mg / kg ) of the racemate resulted in a 57 - 67 % decrease in the spermatogenic index and was at least as effective as a 79 μmol / kg ( 30 mg / kg ) dose of the corresponding analog without the 8 - iodo substituent . in the case of the 8 - bromo or 8 - chloro analogs , the lowest dose tested ( 6 or 2 μmol / kg ; 3 or 1 mg / kg ) was also at least as effective as the 79 μmol / kg ( 30 mg / kg ) dose of the non - halogenated analog ( see table 1 ). comparison of the active ( levo ) enantiomer of the 8 - iodo - 7 - methyl - 4 ′- carbomethoxy analog with the active enantiomer of the 8 - h - 7 - methyl - 4 ′- carbomethoxy analog ( table 2 ) showed the former compound to have the same or greater effect at 0 . 6 and 2 μmol / kg ( 0 . 3 and 1 mg / kg ) as the latter compound at 25 and 75 μmol / kg ( 10 and 30 mg / kg ). thus , an approximately 40 - fold increase in molar potency was achieved by halogenation of the 8 - position . the spermicidal activity of the compounds of the present invention is significantly present with only a single application of composition to ejaculate , with the composition having a concentration of only 3 μm significantly diminishing motility , with motility dropping to zero after application of composition of the present compounds having concentration of only 100 μm . the spermicidal composition of the present invention can have any concentration sufficient to decrease motility of the spermatozoa to a level insufficient to cause impregnation , preferably a concentration of from 1 - 500 μm , more preferably from 3 - 300 μm , most preferably from 10 - 200 μm . spermicidal activity was determined by the method described below . method for determining direct effect of an agent on sperm motility the direct effect of an agent on sperm motility was determined by using the following protocols . basically , sperm are obtained either from the cauda epididymis , as in the case of the rat , or ejaculated sperm collected using an artificial vagina , as in the rabbit . the initial motility of the sperm is determined manually or by using a hamilton thorn ivos sperm analyzer . the sperm are then kept at a constant temperature of 34 ° c ., diluted to a consistent concentration of 10 × 106 / ml , and added to about 3 ml of buffer or media . the motility is determined again at this point and any change is recorded . different concentrations of the agent to be tested are then added to the sperm preparation . the sperm samples are then held at the same temperature for one hour and the motility is determined . the results are recorded as the percent of motile sperm in the sample . protocol for determination of a direct effect of an agent on sperm motility the sperm were kept at 34 ° c . throughout the experimental period . sperm concentration was be approximately 10 × 10 6 / ml ( note , the sample may have had to be diluted with buffer or media to reach this concentration ). a 1 mm stock of the indenopyridine in hbss buffer + bsa ( 5 mg in 10 = 0 . 5 ug / ul ; 0 . 5 ug / ml = 1 um ) was prepared and added as follows : 1 um = 1 ul stock + 949 ul hbss buffer + bsa + 50 ul of the diluted sperm 3 um = 3 ul stock + 947 ul hbss buffer + bsa + 50 ul of the diluted sperm 10 um = 10 ul stock + 940 ul hbss buffer + bsa + 50 ul of the diluted sperm 30 um = 30 ul stock + 920 ul hbss buffer + bsa + 50 ul of the diluted sperm 100 um = 100 ul stock + 850 ul hbss buffer + bsa + 50 ul of the diluted sperm 300 um = 300 ul stock + 650 ul hbss buffer + bsa + 50 ul of the diluted sperm a 1 mm stock of the indenopyridine in m - 199 media with bsa ( 2 . 5 mg in 5 = 0 . 5 ug / ul ; 0 . 5 ug / ml = 1 um ) was prepared and added as follows : 1 um = 1 ul stock + 949 ul m - 199 media with bsa + 50 ul of the diluted sperm 3 um = 3 ul stock + 947 ul m - 199 media with bsa + 50 ul of the diluted sperm 10 um = 10 ul stock + 940 ul m - 199 media with bsa + 50 ul of the diluted sperm 30 um = 30 ul stock + 920 ul m - 199 media with bsa + 50 ul of the diluted sperm 100 um = 100 ul stock + 850 ul m - 199 media with bsa + 50 ul of the diluted sperm 300 um = 300 ul stock + 650 ul m - 199 media with bsa + 50 ul of the diluted sperm slides were made to determine morphology changes and eosin was added to determine cell death . the results of spermicidal tests are shown in table 3 ( rabbit ejaculate ) and table 4 ( rat cauda sperm ) below . the fungicidal activity of the compounds of the present invention can be obtained at any concentration sufficient to reduce the fungal level to a level insufficient to cause fungal infection , and is preferably obtained at concentrations of from 1 - 500 μm , more preferably at concentrations of from 20 - 300 μm , most preferably from 20 - 200 μm . antifungal susceptibility testing was performed following the nccls guidelines with minor modifications . briefly , a suspension of candida albicans cells was prepared from pure cultures grown overnight on yeast - malt extract ( ym ) agar at 35 ° c . several small colonies were removed from a ym agar plate and transferred to 5 ml of 0 . 85 % saline . the cells were suspended by 15 seconds of vortexing and the cell density of the resulting suspension was determined using a spectrophotometer . the cell density was adjusted by addition of 0 . 85 % saline until the transmittance matched that of a 0 . 5 mcfarland standard when measured at a wavelength of 530 nm . an aliquot of this suspension was diluted 1 : 1000 in rpmi - mops to yield a working suspension . a similar suspension of aspergillus fumigatus spores was obtained by using spores stored at 40c in 0 . 85 % saline . these spores were diluted in 0 . 85 % saline to match the mcfarland standard transmittance . this suspension was then further diluted 1 : 50 in rpmi - mops to produce the working inoculum suspension . dilution series of the test compounds were made in rpmi - mops containing 2 % dmso . an aliquot of each dilution was added in duplicate to the wells of a sterile 96 - well , flat bottom microtiter plate . then , an aliquot of either the c . albicans cell suspension or the a . fumigatus spore suspension were added to each well for a final volume of 200 μl . the plates were then incubated at 350c . after 19 hours of incubation , the c . albicans inoculated plates were observed using the unaided eye for determination of minimal inhibitory concentration ( mic ), the concentration for which there was no observable growth . a similar determination was made for the a . fumigatus plates after 48 hours . for all dilutions that exhibited no growth of the test organism , the minimal fungicidal concentration ( mfc ) was determined by streaking 100 μl of medium from a representative well onto a ym agar plate for growth of c . albicans or potato dextrose agar plate for a . fumigatus . the numbers of colony forming units ( cfu ) were counted and these values used to calculate the percent survival of cells or spores in inocula relative to the number of cfus in the working inoculum suspension . the minimum fungicidal concentration ( mfc ) was the lowest concentration of test compound with a percent survival of less than 2 %. the results of fungicide tests are shown in tables 4 - 6 below . table 5 fungicidal activity against a . fumigatus a . fumigatus ( 48 hours ) cfu for compound lowest mfc — [ active ] 300 200 100 4587 - 006 n / a 4587 - 029 100 cidal cidal cidal 4587 - 055 n / a 4587 - 054 n / a 4587 - 054d n / a 4587 - 073d 100 cidal cidal cidal 4587 - 073l 100 cidal cidal cidal 4587 - 040 100 cidal cidal cidal 4587 - 074 n / a 4587 - 0561 100 cidal cidal cidal 4587 - 060 200 not tested cidal 4587 - 037 200 static * cidal 4587 - 065 n / a 4587 - 057 n / a 4587 - 064 100 cidal cidal cidal notes for tables 4 - 5 mfc = minimum fungicidal concentration cfu = colony forming units cidal = & gt ; 98 % killed static = well looked clear , but & lt ; 98 % killed * colonies were too close together to get a good count . likely that it was close to being fungicidal . note that there appeared to be some kind of precipitate in the 073d and 1 wells . perhaps the ppt “ trapped ” the spores . no other compounds showed this ppt . precursors for the compounds of the invention can be prepared by the method disclosed in u . s . pat . no . 5 , 319 , 084 using modifications of the method disclosed in u . s . pat . no . 3 , 678 , 057 . these patents are incorporated herein by reference in their entirety . the r 3 substituents are introduced into the molecule by using an appropriate grignard reagent or phenyl lithium reagent . the mixtures of enantiomers produced by this process are resolved into pure enantiomers by salt formation followed by selective crystallization or chromatography . for example , resolution of compound 1 can be effected by salt formation with s (+) and r (−)- 2 , 2 ′-( 1 , 1 ′- binaphthyl ) phosphoric acid and resolution of compound 3 can be effected by salt formation with r - and s - mandelic acid as described in c . e . cook et al , j . med . chem ., 38 : 753 ( 1995 ). optical purity is established by high pressure liquid chromatography ( hplc ) on a chircel - od column . compounds of this invention may be prepared beginning with carboxylic acid 2 or one of its esters ( for example , 3 ). compounds such as 2 and 3 are prepared as described in u . s . pat . no . 5 , 319 , 084 . alternatively , they may be made by the process shown in fig2 , where an n - substituted - 3 - arylhexahydropyridine - 4 - carboxylic acid ester ( 4 ) is hydrolyzed to carboxylic acid 5 , which is then treated with thionyl chloride to yield acid chloride 6 . treatment of this compound with alcl 3 cyclizes the compound to the tricyclic ketone 7 . reaction of ketone 7 with a p - halogen - substituted phenyl magnesium halide or p - halogen - substituted phenyl lithium ( 4 - bromophenyl lithium ) forms tertiary alcohol 8 , which upon treatment with a trialkylsilane , for example a tri - c 1 - 6 alkyl silane such as triethylsilane and bf 3 is reduced to compound 9 , which is then refluxed with a strong base ( e . g . koh ) in an alcohol solvent , preferably high boiling , such as n - butanol to yield bromophenyl compound 10 having the desired stereochemistry . conversion of the bromophenyl group to a lithiophenyl group , for example with a c 1 - 6 alkyl li compound , and carboxylation ( co 2 ) using known reagents yields carboxylic acid 2 , which may be esterified by conventional means well known in the art , for example reaction with a c 1 - 6 alkanol , to obtain ester 3 . the synthesis noted above may be modified to provide an enantioselective synthesis of the active enantiomers of compounds 2 and 3 , which may then be used to synthesize the active enantiomers of the present invention as shown in fig3 . thus , an n - substituted 1 , 2 , 5 , 6 - tetrahydropyridine - 4 - carboxylic acid ( for example , 12 ) is converted to its acid chloride and the latter compound is used to acylate 1r (+)-( 2 , 10 )- camphorsultam or 1s (−)-( 2 , 10 )- camphorsultam . when the resulting enoylsultam ( 13 ) is treated with an aryl magnesium halide it undergoes 1 , 4 - addition with high diastereofacial selectivity to introduce an aryl group at the 3 - position in high enantiomeric excess . crystallization yields pure enantiomer 14 . the amide function is hydrolyzed and the chiral adjuvant may then be recovered . the carboxylic acid is then converted to tricyclic ketone 7 as described above . this compound can be converted to essentially enantiomerically pure 2 and 3 by treatment with bromophenyl lithium and subsequent steps as shown in fig2 . alternatively , chiral ketone 7 may be converted to an enantiomerically enriched 2 and 3 by the procedure described for synthesis of racemates in u . s . pat . no . 5 , 319 , 084 . the degree of enrichment is dependent upon catalyst and temperature in the reduction of the enantiomeric tetrahydroindeno pyridine analogous to intermediate 5 . see fig3 of u . s . pat . no . 5 , 319 , 084 . thus , there was 73 % enantiomeric excess ( cc ) at 23 ° c . with pdcl 2 / nabh 4 / 3 atm h 2 , but complete racemization at 55 ° c . ; whereas with pt / c / h 2 the ee at 60 ° c . was comparable to that at 23 ° c . ( 67 % and 70 %, respectively ). either carboxylic acid 2 or its esters , such as methylester 3 , may be iodinated to yield the 8 - iodo analogs 17 or 18 by reaction with iodine under oxidizing conditions or with an oxidized form of iodine ( fig4 ). for example , reaction of 3 with about 1 mol of iodine in the presence of mercuric oxide leads in high yield to 8 - iodo compound 18 . the ester and acid are interconvertible by standard chemical techniques well known in the art . either the racemates or enantiomers may be used . one may also use a radioactive isotope of iodine , such as 125 i , 123 i or 131 i to yield a radio - labeled analog of 17 or 18 . such compounds are useful for determining the localization and site of action of these compounds and may be used as imaging agents for diagnosis of male reproductive disorders . the iodo compounds , in particulars the 8 - iodo acid 17 , may be converted to the bromo and chloro compounds by formation of a metal salt of the acid , for example , the sodium salt , and then by formation of an 8 - metal intermediate where the metal is a metal such as lithium or a substituted metal with known reagents such as t - buli . reaction of the 8 - metal intermediate with a halogen source such as hexachloroethane or 1 , 2 - dibromoethylene leads to the corresponding 8 - substituted analogs , such as compounds 19 or 20 shown in fig4 . the corresponding fluoro compounds can be prepared by reacting the 8 - metal intermediate with chlorotrimethylsilane to form the corresponding 8 - trimethylsilyl compound and then reacting this compound with lead tetra - acetate in the presence of bf 3 - et 2 o . see de mio et al , 1993 , tetrahedron , 49 : 8129 - 8138 . one may obtain radioactive analogs of the various subject compounds by , for example , treating the 8 - metal intermediate with a reagent containing an electrophilic halogen atom as its radioactive isotope or , as pointed out earlier , one can make the radioactive analogs of compounds 17 or 18 by substituting a radioactive isotope of iodine in the synthesis of the compounds described above . tritium - labeled compound of the invention may be obtained , for example , by reduction of the 8 - iodo compounds with tritium gas catalyzed by a noble metal , such as palladium or platinum . carbon - 14 analogs may be made , for example , by using 14 c labeled carbon dioxide in step “ g ” of the synthesis of compound 2 as shown in fig2 . other methods for isotopic labeling of the compounds commonly used in the art of radiochemical synthesis may also be applied . the compounds of the present invention are useful as male antifertility drugs for controlling fertility in mammals , including humans . in addition to their potential use in family planning , the compounds of the invention are also useful to control fertility in domestic , wild or feral animals , where lethal measures are not practical or desirable . for example , the control of deer populations is a problem in some areas of the united states . oral administration of the compounds of the present invention to seasonal breeding animals such as deer by means of baited feed containing these compounds at appropriate times would substantially reduce reproductive capacity . other target animals include rodents such as mice , rats , prairie dogs , etc ., as well as feral goats , swine , horses , etc . administration of the compounds of this invention to captive zoo animals provides a means of controlling reproduction in species which become overpopulated . by “ controlling fertility ” as used herein is meant reducing the reproductive capacity or fertility of the mammal treated . the length of infertility is a function of dose such that with sufficient doses one may extend the period of infertility so as to essentially use the compounds of this invention to perform sterilization ; thus , the compounds of the invention may replace surgical vasectomy as a means of male sterilization . when performing such sterilization , the compounds of the invention are administered in a single dose or a plurality ( two or more ) of doses where the doses are sufficient to reduce the sperm producing ability of the mammal ( spermatogenic index ) to a level of infertility . that is , the compounds of the invention are administered in an amount and for a length of time sufficient to reduce the sperm count to a level which is not sufficient to reproduce . for the above - mentioned uses , the dose of the compound of the invention will naturally vary depending on the specific compound employed , the mode of administration and the length of infertility desired . however , satisfactory results are obtained in animals at oral doses from about 0 . 02 to about 10 mg / kg , preferably about 0 . 1 - 3 mg / kg body weight per day . for larger animals , a daily dose amount of about 10 - 100 mg may be administered as a single oral unit dose or in divided dosage units containing about 0 . 1 - 10 mg of the compound of the present invention . when administering a single active enantiomer , one may generally administer a smaller dose then when administering a racemic compound . if desired or necessary , the compounds of the invention may be administered together with solid or liquid carriers or diluents or in slow - release form . formulation of these pharmaceuticals forms is well known in the art and any conventional method of preparing solid , liquid and slow - release formulations may be used with the compounds of the present invention . the compounds of the invention may also be administered by means of conventional implants or skin patches which are well known in the art . the compounds of the invention may be used in human contraception in males , either by reversibly blocking spermatogenesis or in nonsurgical sterilization . in the latter use , administration of appropriately large doses realizes the effects of vasectomy without the use of surgery and with the elimination of potential side effects of vasectomy . the compounds of the invention are also useful in the control of reproduction in domestic , wild , feral or zoo animals for example , the compounds may be in the control of reproduction in zoo animals . wild and feral animal populations close to human habitation , for example deer , or animal populations which strongly impact the natural ecology , for example wild mustangs and feral hogs , may be controlled by selectively baiting without using lethal means such as shooting or poisoning . animal behavior is not affected in this process , only fertility . when r 4 is a radioactive label , the compounds of the invention are useful to study testicular function and diagnose testicular malfunction . administration of the compounds in the dosages noted above binds to testicular tissue . in their anti - spermatogenic properties , the high degree of chemo -, stereo - and enantioselectivity of the compounds together with their lack of general effects , such as on libido , indicates that they are interacting with a specific macromolecule in the testis . treatment of testis or testis fractions with a radioactive derivative of the compounds followed by detection of radioactivity by techniques well known in the art of radiochemistry enable one to locate and identify the portion of the testis and the macromolecule involved in the antispermatogenic effect . this may be used to detect and identify an important constituent of the testis , disruption of which can lead to an antifertility effect . comparison of the ability of other compounds ( such as analogs of the current compounds or those from combinatorial libraries ) to inhibit the binding of the radiolabeled compound can lead to even more selective and potent antispermatogenic compounds . furthermore , by administering a small dose ( too small to have a clinical effect on fertility ) of the radiolabeled compound to an animal or human subject and then measuring the amount of radioactivity in the testis or specific areas of the testis , one can show whether an existing problem of infertility is related to the lack of this macromolecule . the radioactivity can be measured in a living animal or human by techniques such as pet and spect which are well known in the art of imaging of biological tissues . the compounds are also useful as internal standards for analytical purposes . thus for example a compound such as 20 may be added in known quantity to a sample of blood , plasma or tissue from an animal or human dosed with compound 17 . the sample of blood , plasma or tissue may then be extracted with an organic solvent and the extract subjected to analytical high performance liquid chromatography or to gas chromatography , either with or without conversion to a derivative such as the methyl ester . measurement of the areas of the chromatographic peaks associated with 17 and 20 and comparison to the area ratios of known amounts of 17 and 20 subjected to the same conditions enable one to determine the concentration of 17 in the sample of blood , plasma or tissue . because of the close structural resemblance between 17 and 20 , the physicochemical properties of the two compounds will be similar for extraction , thus making one an almost ideal standard for the other . for use as a spermicide , the compounds of the present invention can be prepared in a variety of forms for administration . conventional spermicidal composition forms are readily prepared using known methods . such spermicidal compositions can take the form of gels , foams , jellys , creams , ointments , salves , etc . conventional carriers are used to prepare the compositions . the present spermicidal compositions can be administered alone or in combination with one or more barrier methods of contraception , such as a diaphragm , sponge or condom . the composition can be applied directly to the diaphragm , sponge or condom immediately prior to use , or can be prepackaged along with the sponge or condom ( or even diaphragm , although most diaphragms are for multiple uses and are cleaned between uses ). for use as a fungicide , the composition of the present invention can be prepared in any suitable form for administration to the area in need thereof . the forms of administration include , but are not limited to , those listed above for spermicidal compositions , as well as liquid mixtures . it is also possible for the fungicidal and spermicidal properties to be used in combination using one of the common forms of administration . other features of the present invention will become apparent in the course of the following descriptions of exemplary embodiments which are given for illustration of the invention and are not intended to be limiting thereof . iodoethane ( 540 g , 3 . 41 mol ) in methanol ( 500 ml ) was added to ethyl isonicotinate ( 500 g , 3 . 31 mol ). the mixture was refluxed gently overnight . sodium borohydride ( 140 g ) was added portionwise to the above solution under cooling ( ice bath ). after the addition of nabh 4 was complete , the mixture was stirred at room temperature overnight . most of the methanol was evaporated , water and ether were added to the solution and ether layer was separated . evaporation of dry ether ( na 2 so 4 ) layer gave an oil . distillation of this red oil gave a yellowish oil 470 g , 78 %): bp 160 ° c . at 0 . 5 mm . the above compound ( 146 g , 0 . 8 mol ) in dry ether ( 200 ml ) was added dropwise to 1m p - tolylmagnesium bromide in ether ( 600 ml , 1 . 6 mol at − 10 ° c .). after being stirred for 3 h , the reaction mixture was poured into 10 % aqueous nh 4 cl solution ( 200 ml ). the aqueous layer was extracted with ether . evaporation of the dry ( na 2 so 4 ) ether layer gave a yellowish brown oil . this oil was dissolved in 18 % aqueous hcl ( 500 ml ) and extracted with ether . the aqueous hcl solution was refluxed for 2 h . evaporation of the solvent gave the corresponding amino acid ( 181 g , yield 80 %), which ( 32 g ) was mixed with polyphosphoric acid ( 500 g ) and stirred vigorously at 140 ° c . for 3 h . the reaction mixture was cooled and 50 % koh aqueous solution was added cautiously . the basified solution was extracted with ether . evaporation of the dry ( na 2 so 4 ) ether layer gave 2 - ethyl - 7 - methyl - 2 , 3 , 4 , 4a . alpha ., 5 , 9b . alpha .- hexahydro - 1h - indeno [ 1 , 2 - c ] pyridin - 5 - one as an oil ( 22 . 6 g , 87 %). an analytical sample was obtained by passing through a small column of sio 2 using a gradient of meoh in chcl 3 ( 0 - 5 %): 1 h nmr ( 90 mhz , cdcl 3 ) δ7 . 5 ( 1h , s , h - 6 ), 7 . 3 ( 2h , m , h - 8 , h - 9 ), 3 . 5 ( 1h , m ), 3 . 0 ( 1h , m ), 2 . 6 ( 2h , m ), 2 . 3 ( 3h , s , 7 - me ), 2 . 2 ( 3h , m ), 1 . 9 - 1 . 7 ( 3h , m ), 1 . 1 ( 3h , t , me ); hrms ( m +): calcd . for c 15 h 19 no : m / z 229 . 1467 . found : m / z 229 . 1466 . to a mechanically stirred solution of para - bromobenzoic acid ( 1 . 6 g , 8 . 0 mmol ) in tetrahydrofuran ( thf ) ( 15 ml ) at − 78 ° c . was added n - butyllithium ( 16 . 2 mmol , 6 ml of a 2 . 5m solution in hexane ) dropwise over a 45 min period . after the mixture was stirred for an additional 1 . 5 h , the tricyclic ketone ( 1 . 1 g , 5 . 1 mmol ) was added as a solution in thf ( 5 ml ) dropwise over a 30 min period and stirring was continued for 2 . 5 h at − 78 ° c . the mixture was poured into ice cold 1m hcl ( 75 ml ) and extracted with ether ( 2 × 30 ml ). the acidic aqueous layer was stirred for 15 h at room temperature and concentrated under reduced pressure to afford a solid . this solid was purified via flash column chromatography on silica with a gradient elution of 10 - 20 % meoh in chcl 3 and yielded 2 - ethyl - 7 - methyl - 2 , 3 , 4 , 9b - tetrahydro - 5 -( p - carboxyphenyl )- 1h - indeno [ 1 , 2 - c ] pyridine hydrochloride as a yellow solid ( 1 . 1 g , 58 %). 1 h nmr ( 250 mhz , cdcl 3 ), δ1 . 54 ( 3h , t , j = 7 . 2 hz ), 2 . 35 ( 3h , bs ), 2 . 25 - 2 . 42 ( 1h , m ), 2 . 50 - 2 . 72 ( 1h , m ), 2 . 94 - 3 . 0 ( 1h , m ), 3 . 15 - 3 . 30 ( 2h , m ), 3 . 50 - 3 . 80 ( 2h , m ), 4 . 17 - 4 . 30 ( 1h , m ), 4 . 40 - 4 . 52 ( 1h , m ), 7 . 0 - 7 . 12 ( 2h , m ), 7 . 32 ( 1h , d , j = 7 . 5 hz ), 7 . 45 ( 2h , d , j = 8 . 4 hz ), 8 . 20 ( 2h , d , j = 8 . 4 hz ). hrms ( m +) calcd . mw for c 22 h 23 no 2 : m / z 333 . 1729 . found : m / z 333 . 1725 . to a solution of the above compound ( 379 mg , 1 . 03 mmol ) in ethanol / water ( 40 ml of a 1 : 1 mixture ) was added nacl ( 81 mg ), pdcl 2 ( 98 mg ), nabh 4 ( 100 mg ), and concentrated hcl ( 10 drops ). after the mixture was shaken on a parr apparatus under a hydrogen atmosphere ( 45 psi ) at 50 ° c . for 15 h , it was filtered through celite and concentrated under reduced pressure . the resulting solid was suspended in absolute ethanol , filtered through celite , and the filtrate was concentrated under reduced pressure to yield ( 4ars , 5rs , 9brs ) 2 - ethyl - 7 - methyl - 2 , 3 , 4 , 4a , 5 , 9b - hexahydro - 5 -( p - carboxyphenyl )- 1h - indeno [ 1 , 2 - c ] pyridine hydrochloride . 1 h nmr ( 250 mhz , cdcl 3 ): δ1 . 4 ( 3h , t , 7 . 2 hz ), 1 . 50 - 1 . 60 ( 1h , m ), 1 . 85 - 2 . 00 ( 1h , m ), 2 . 20 ( 3h , s ), 2 . 20 - 2 . 40 ( 1h , m ), 2 . 70 - 2 . 90 ( 3h , m ) 2 . 90 - 3 . 15 ( 2h , m ), 3 . 50 - 3 . 65 ( 1h , m ), 3 . 90 - 4 . 10 ( 1h , m ), 4 . 50 ( 1h , d , j = 7 . 3 hz ), 6 . 95 , ( 1h , bs ), 7 . 10 ( 1h , d , j = 7 . 5 hz ), 7 . 20 ( 1h , d , j = 7 . 5 hz ), 7 . 30 , ( 2h , d , j = 8 . 0 hz ), 8 . 00 ( 2h , d , j = 8 . 0 hz ). hrms ( m +) calcd . mw for c 22 h 25 no 2 : m / z 335 . 18853 . found : m / z 335 . 1887 . to a solution of potassium hydroxide ( 15 g ) in n - butanol ( 60 ml ) was added the above compound ( 2 . 99 g , 8 . 0 mmol ) in one portion . after being refluxed for 20 h , the dark brown mixture was cooled to 0 ° c . and acidified to ph = 1 with 18 % hcl . the solvent was removed in vacuo to afford a yellow solid . this solid was taken up in chcl 3 , filtered through celite , and the filtrate was concentrated in vacuo to afford crude ( 4ars , 5sr , 9brs ) 2 - ethyl - 7 - methyl - 2 , 3 , 4 , 4a , 5 , 9b - hexahydro - 5 -( p - carboxyphenyl )- 1h - indeno [ 2 , 2 - c ] pyridine hydrochloride as an off - white solid . this solid was purified via flash column chromatography using 10 % meoh — chcl 3 and yielded 1 . 23 g ( 41 %) of the title compound as a white solid . m . p .= 280 ° c . ( dec .) 1 h nmr ( 250 mhz , cdcl 3 — cd 3 od ). δ1 . 45 ( 3h , t , j = 7 . 3 hz ), 1 . 8 ( 1h , bd , j = 14 . 7 hz ), 2 . 2 ( 3h , s ), 2 . 4 - 2 . 7 ( 2h , m ), 3 . 0 - 3 . 4 ( 4h , m ), 3 . 4 - 3 . 7 ( 2h , m ), 3 . 7 - 4 . 0 ( 1h , m ), 4 . 2 ( 1h , d , 11 hz ), 6 . 6 ( 1h , bs ), 7 . 0 - 7 . 2 ( 4h , m ), 8 . 0 ( 1h , d , j = 7 . 7 hz ). hrms ( m +) calcd . mw for c 22 h 25 no 2 : m / z 335 . 18853 . found : m / z 335 . 18830 . anal . calcd . for c 22 h 26 clno 2 ½h 2 o : c , 69 . 37 ; h , 7 . 14 ; n , 3 . 68 . found : c , 69 . 72 ; h , 7 . 15 ; n , 3 . 55 . to a solution of the carboxylic acid of example 1 ( 3 . 6 g , 9 . 69 mmol ) in methanol ( 50 ml ) at − 10 ° c . was added thionyl chloride ( 1 . 1 ml , 14 . 5 mmol ) over a 10 min period . the resulting solution was allowed to stand in a refrigerator at 5 ° c . for 68 h during which time the product had begun to crystallize out as fine white needles . three crops were obtained and combined to yield 2 . 65 g of the title compound . mp = 204 ° c . ( sublimed ). 1 h nmr ( 250 mhz , cdcl 3 ): δ1 . 1 ( 3h , t , j = 7 . 2 hz ), 1 . 6 ( 1h , bd , j = 14 . 2 hz ), 1 . 80 - 2 . 00 ( 2h , m ), 2 . 1 - 2 . 2 ( 1h , m ), 2 . 2 ( 3h , s ), 2 . 4 ( 2h , q , j = 7 . 2 hz ), 2 . 5 - 2 . 6 ( 1h , m ), 2 . 7 - 2 . 8 ( 1h , m ), 2 . 9 ( 1h , dd , j = 5 . 94 , 11 . 64 hz ), 3 . 3 - 3 . 4 ( 1h , m ), 3 . 9 ( 3h , s ), 4 . 2 ( 1h , d , j = 10 . 0 hz ), 6 . 7 ( 1h , bs ), 7 . 0 ( 1h , d , j = 7 . 5 hz ), 7 . 2 ( 1h , d , j = 7 . 5 hz ), 7 . 3 ( 2h , d , j = 8 . 0 hz ), 8 . 0 ( 2h , d , 8 . 0 hz ). anal . calcd . for c 23 h 28 clno 2 ¼h 2 o : c , 70 . 75 ; h , 7 . 36 ; n , 3 . 59 . found : c , 70 . 67 ; h , 7 . 36 ; n , 3 . 59 . to a stirring solution of ( 4ars , 5sr , 9brs )- 2 - ethyl - 2 , 3 , 4 , 4a , 5 , 9b - hexahydro - 7 - methyl - 5 -( 4 - carbomethoxy phenyl )- 1h - indeno [ 1 , 2 - c ] pyridine ( 341 mg , 0 . 88 mmol ) in glacial acetic acid ( 2 ml ) was added 62 % hclo 4 ( 1 ml ) followed by hgo ( 205 mg , 0 . 95 mmol ). the mixture was briefly sonicated in order to effect a homogenous solution . a solution of iodine ( 235 mg , 0 . 925 mmol ) in glacial acetic acid ( 17 ml ) was added dropwise over 15 min and the resulting mixture was stirred at room temperature overnight . the orange - red mixture was poured into water ( 100 ml ), cooled to 5 ° c ., basified to ph 12 with 30 % naoh , and extracted with ether ( 3 × 75 ml ). the clear , colorless ether extracts were combined , washed successively with water ( 20 ml ) and brine ( 30 ml ), dried ( mgso 4 ), filtered , and concentrated in vacuo to afford the crude free base of 18 ( 448 mg ). this material was transformed into the hcl salt using 3 % methanolic hydrogen chloride and recrystallized from etoac — meoh . yield = 400 mg ( 89 %). m . p .=& gt ; 190 ° c . ( dec .). 1 h nmr ( 250 mhz , cdcl 3 , as free base ); δ1 . 15 ( 3h , t , j = 7 . 2 hz ), 1 . 65 ( 1h , bd ), 1 . 8 - 2 . 1 ( 3h , m ), 2 . 32 ( 3h , s ), 2 . 48 ( 3h , q , j = 7 . 2 hz , + m ), 2 . 80 ( 1h , bd ), 2 . 97 ( 1h , dd , j = 11 . 8 , 5 . 8 hz ), 3 . 41 ( 1h , m ), 3 . 91 ( 3h , s ), 4 . 19 ( 1h , d , j = 9 . 8 hz ), 6 . 78 ( 1h , s ), 7 . 22 ( 2h , d , j = 8 . 3 hz ), 7 . 73 ( 1h , s ), 8 . 00 ( 2h , d , j = 8 . 3 hz ). hrms : calcd . for c 23 h 26 no 2 i , ( corresponding to the free base ): m / z 475 . 1008 . found : m / z 475 . 1004 . anal . calcd . for c 23 h 27 clino 2 ½h 2 o : c , 53 . 04 ; h , 5 . 42 ; n , 2 . 69 . found : c , 52 . 70 ; h , 5 . 60 ; n , 2 . 57 . the active enantiomer , ( 1 )- 18 , was synthesized in a similar fashion starting from ( 1 )- 3 . [ α ] d =− 5 . 6 ( c = 1 . 18 , chcl 3 ). to ( 4ars , 5sr , 9brs )- 2 - ethyl - 2 , 3 , 4 , 4a , 5 , 9b - hexahydro - 7 - methyl - 5 -( 4 - carboxyphenyl )- 1h - indeno [ 1 , 2 - c ] pyridine hydrochloride ( 250 mg , 0 . 673 mmol ) in 2 ml of acetic acid was added 6 ml of a 1 : 1 mixture of acetic acid and perchloric acid . hgo ( 1 . 35 mmol ) was added and the reaction mixture was stirred at room temperature until the hgo dissolved . a solution of i 2 ( 427 mg , 1 . 68 mmol ) in 4 ml of acetic acid and 6 ml of ch 2 cl 2 was added dropwise the reaction mixture by addition funnel . the reaction mixture was stirred overnight at room temperature and then filtered through celite . the red solid was washed with water and ch 2 cl 2 . the combined biphasic filtrate was separated by separatory funnel . the organic phase was washed with saturated sodium bisulfite solution , dried over sodium sulfate ( anhydrous ), filtered and concentrated to give 234 mg of yellow brown solid , converted to the hydrochloride in the usual way . 1h nmr ( 250 mhz , cdcl 3 / cd 3 oh ) δ1 . 28 ( 3h , t , j = 7 . 2 hz ), 2 . 0 - 2 . 1 ( 1h , m ), 2 . 3 ( 3h , s ), 2 . 56 ( 2h , m ), 3 . 04 ( 3h , m ), 3 . 24 ( 1h , m ), 3 . 46 ( 2h , m ), 4 . 18 ( 1h , d , j = 11 hz ), 6 . 73 ( 1h , s ), 7 . 13 ( 2h , d , j = 8 . 2 hz ), 7 . 71 ( 1h , s ), 7 . 89 ( 2h , d , j = 8 . 2 hz ). hrms calcd for c 22 h 24 no 2 i ( corresponding to the free base ): m / z 461 . 0852 ; found : m / z 461 . 0857 . ( 4ars , 5sr , 9brs )- 2 - ethyl - 8 - iodo - 7 - methyl - 2 , 3 , 4 , 4a , 5 , 9b - hexahydro - 5 -( 4 - carboxylphenyl )- 1h - indeno [ 1 , 2 - c ] pyridine hydrochloride ( 200 mg , 0 . 402 mmol ) was dissolved in 20 ml thf and 0 . 4 ml hexamethylphosphoramide . to this solution was added 50 mg sodium hydride ( 60 % in mineral oil ). the mixture was refluxed for 1 h and then cooled to − 78 ° c . tert - butyllithium solution ( 0 . 73 ml , 1 . 1 m in pentane , 0 . 804 mmol ) was added slowly . after the addition the mixture was stirred at − 78 ° c . for 20 min . 1 , 2 - dibromoethylene ( 1 ml ) was added . the mixture was stirred at − 78 ° c . for another 30 min and then warmed to room temperature . 5 % hydrochloric acid was added to the solution until the solution became acidic . the mixture was extracted with methylene chloride . the methylene chloride solution was washed with brine and dried over mgso 4 . the crude product was purified with flash column chromatography ( silica ; methylene chloride and methanol , 10 : 1 ) to afford the title compound : 30 mg , 17 % yield , m . p ., 169 . 6 - 170 . 3 ° c . 1 h nmr ( 250 mhz , d 2 o — cdcl 3 ), δ1 . 25 ( 3h , t , j = 7 . 0 hz ), 1 . 72 ( 1h , d , j = 15 hz ), 1 . 90 - 2 . 15 ( 1h , m ), 2 . 19 ( 3h , s ), 2 . 36 ( 1h , t , j = 12 . 5 hz ), 2 . 5 - 2 . 65 ( 1h , m ), 2 . 7 - 3 . 0 ( 3h , m ), 3 . 2 - 3 . 4 ( 4h , m ), 3 . 4 - 3 . 6 ( 1h , m ), 1h , m ), 4 . 13 ( 1h , d , j = 10 . 5 hz ), 6 . 71 ( 1h , s ), 7 . 11 ( 2h , d , j = 8 . 0 hz ), 7 . 43 ( 1h , s ), 7 . 89 ( 2h , d , j = 8 . 0 hz ). ms : 413 ( m ). anal . ( c 22 h 25 o 2 brcln1 . 8h 2 o ): calculated c 54 . 68 , h 5 . 22 , n 2 . 90 ; found c 54 . 77 , h 5 . 52 , n 2 . 57 . hrms calcd for c 22 h 24 no 2 br ( corresponding to the free base ): m / z 413 . 0990 . found : m / z 413 . 0994 . ( 4ars , 5sr , 9brs )- 2 - ethyl - 8 - iodo - 7 - methyl - 2 , 3 , 4 , 4a , 5 , 9b - hexahydro - 5 -( 4 - carboxylphenyl )- 1h - indeno [ 1 , 2 - c ] pyridine hydrochloride ( 250 mg , 0 . 5 mmol ) was dissolved in 25 ml thf and 0 . 5 ml hmpa . to this solution was added 60 mg sodium hydride ( 60 % in mineral oil ). the mixture was refluxed for 1 h and then cooled to − 78 ° c . tert - butyllithium solution ( 0 . 91 ml , 1 . 1 m in pentane , 1 . 04 mmol ) was added slowly . after the addition the mixture was stirred at − 78 ° c . for 20 min . a solution of hexachloroethane ( 2 . 46 g , 10 . 4 mmol ) in 2 ml thf was added . the mixture was stirred at − 78 ° c . for another 30 min . and then warmed to room temperature . 5 % hydrochloric acid was added to the solution until the solution became acidic . the mixture was extracted with methylene chloride . the methylene chloride solution was washed with brine and dried over mgso 4 . the crude product was purified with flash column chromatography ( methylene chloride and methanol , 10 : 1 ) to afford the title compound , 60 mg , 30 % yield . 1 h nmr ( 250 mhz , d 2 o — cdcl 3 ) δ1 . 35 ( 3h , t , j = 7 . 25 hz ), 1 . 75 - 1 . 95 ( 1h , m ), 2 . 30 ( 3h , s ), 2 . 45 - 2 . 75 ( 2h , m ), 2 . 80 - 3 . 15 ( 2h , m ), 3 . 20 - 3 . 50 ( 4h , m ), 3 . 50 - 3 . 70 ( 1h , m ), 4 . 25 ( 1h , d , j = 10 hz ), 6 . 80 ( 1h , s ), 7 . 25 ( 2h , d , j = 7 . 5 hz ), 7 . 32 ( 1h , s ), 8 . 0 ( 2h , d , j = 7 . 5 hz ). ms : 370 ( m ) anal . ( c 22 h 25 o 2 cl 2 n ): calculated c 65 . 50 , h 6 . 20 , n 3 . 45 ; found c 65 . 65 , h 6 . 73 , n 3 . 59 . hrms calcd for c 22 h 24 no 2 cl ( corresponding to the free base ): m / z 369 . 1495 . found : m / z 369 . 1494 . crude methyl 1 - ethyl - 3 -( 4 - methylphenyl )- 4 - pyridinecarboxylate ( prepared as described in u . s . pat . no . 5 , 319 , 084 for the analogous ethyl ester ) from 165 g of methyl 1 - ethyl - 1 , 2 , 5 , 6 - tetrahydropyridinecarboxylate was dissolved in 1 l of aqueous 18 % hcl and extracted with ether ( 300 ml ) to remove bitolyl remaining as a byproduct from its synthesis . the aqueous solution was then refluxed for 48 hr and then concentrated under reduced pressure with added acetonitrile ( azeotrope ) to give crude 1 - ethyl - 1 , 2 , 5 , 6 - tetrahydropyridinecarboxylic acid hydrochloride ( 283 g ), which was dried thoroughly at 100 ° c . under high vacuum . as this material is very hygroscopic , it was stored under nitrogen . thionyl chloride ( 150 ml ) was added cautiously to neat 7 ( 45 g , 159 mmol ) at 5 ° c . after the addition , the ice bath was removed ; and the resulting homogeneous solution was stirred at room temperature for 4 h . excess socl 2 was removed in vacuo to give a dark , thick , pasty mass . to this material was added 1 , 2 - dichloroethane ( 250 ml ) and 30 ml of solvent was removed in vacuo in order to remove any residual socl 2 . to the turbid mixture was added alcl 3 ( 53 g , 397 mmol ) in portions over a 45 min period . the temperature was controlled by means of a water bath at ca . 25 ° c . after the addition , the dark , red - brown , solution was stirred at 35 - 40 ° c . for an hour and then poured into a beaker containing ca . 400 g of crushed ice and 50 ml of conc . hcl . the aqueous layer was basified to ph of ca . 12 with 30 % naoh ( ca . 350 ml ) with cooling in an ice water bath . the resulting mixture was extracted with cooling in an ice water bath . the resulting mixture was extracted with ether ( 3 × 400 ml ), and the combined ether layers were washed successively with water and brine , dried ( mgso 4 ), filtered , and concentrated under reduced pressure to give an orange - red oil . this oil was distilled using a kugelrohr apparatus ( 125 - 135 ° c . at 0 . 5 mm hg ) to give 21 . 6 g ( 59 %) of ketone 7 as a bright yellow solid , with nmr properties identical with authentic material . enantiomers are described as ( d ) or ( l ) based on optical rotation at the sodium d line in the solvent given . compounds having the same sign of rotation do not necessarily have the same absolute configuration . 1 - ethyl - 4 - carboxy - 1 , 2 , 5 , 6 - tetrahydropyridine hydrochloride . methyl 1 - ethyl - 1 , 2 , 5 , 6 - tetrahydropyridinecarboxylate ( 11 ) was refluxed in 250 ml of 1 . 5 m hcl for 4 h . the mixture was concentrated to dryness using applied heat and a stream of nitrogen to give a highly crystalline solid . the solid was recrystallized from meoh and gave 19 . 6 g of the hcl salt of 12 ; m . p .= 265 ° c . ( dec .). anal . calcd . for c 8 h 14 clno 2 : c , 50 . 14 ; h , 7 . 36 ; n , 7 . 31 . found : c , 50 . 23 ; h , 7 . 36 ; n , 7 . 28 . ( 1 )- enoyl sultam (( 1 )- 13 ) derived from 1s (−)-( 2 , 10 ) camphorsultam ). to the hydrochloride of 12 ( 1 . 3 g , 6 . 79 mmol ) was added thionyl chloride ( 15 ml ), and the resulting mixture was heated to reflux for 2 h . excess socl 2 was removed in vacuo , and the residue was triturated with 10 ml of dry toluene and concentrated in vacuo . the trituration process was repeated two more times to give a yellow , powdery solid . in a separate vessel , n - butyllithium ( 15 mmol , 6 . 0 ml of a 2 . 5 m solution in hexane ) was added dropwise to a solution of 1s -(−)- 2 , 10 - camphorsultam ( 3 . 16 g , 14 . 7 mmol ) in thf ( 30 ml ) at 5 ° c . after the addition , the clear , colorless solution was brought to room temperature and stirred for an additional 45 min . the solution of sultam anion was then cannulated into the flask containing the amino acid chloride hydrochloride at 5 ° c . after the addition , the orange mixture was allowed to come to room temperature and stirred for 18 h . the reaction was quenched by the addition of saturated nh 4 cl ( ca . 1 ml ) and concentrated in vacuo to a brown , tarry residue . the residue was partitioned between ether and water , and the ether layer was washed once more with water . the ether layer was then washed with dilute aqueous hcl ( ca . 5 %) and separated . the free sultam ( ether layer ) was obtained ( 1 . 2 g ) upon recrystallization from absolute etoh . the product [( 1 )- 13 ] was obtained by basifying the acidic aqueous layer with conc . nh 4 oh to ph 12 , extraction with ether and recrystallization from n - hexane of the residue from evaporation of the ether layer . this gave 1 . 9 g of ( 1 )- 13 as white , thick needles ; m . p .= 120 ° c ., [ a ] d 21 =− 74 . 8 ° ( c = 1 . 0 , chcl 3 ), 1 h nmr identical with its antipode ( see below ). anal . calcd . for c 8 h 28 n 2 o 3 s : c , 61 . 33 ; h , 8 . 01 ; n , 7 . 95 . found : c , 61 . 35 ; h , 8 . 06 ; n , 7 . 89 . ( d )- enoyl sultam enantiomer of 13 derived from 1r (+)-( 2 , 10 )- camphorsultam . this was prepared from the hydrochloride of amino acid 12 ( 6 . 5 g , 34 . 1 mmol ) and 1r -(+)- 2 , 10 - camphorsultam ( 15 . 4 g , 71 . 4 mmol ) in a procedure similar to that described for the antipode ( see above ) in 86 % yield . m . p .= 118 . 5 ° c .- 119 . 6 ° c . ( recrystallized from hexane as thick , straw - colored leaflets ); [ α ] d 21 =+ 74 . 1 ° ( c = 1 . 0 , chcl 3 ); 1 h nmr ( 250 mhz , cdcl 3 ): δ1 . 00 ( 3h , s ), 1 . 12 ( 3h , t , j = 7 . 1 hz ), 1 . 22 ( 3h , s ), 1 . 3 - 1 . 5 ( 2h , m ), 1 . 8 - 2 . 1 ( 5h , m ), 2 . 2 - 2 . 4 ( 1h , m ), 2 . 55 ( 2h , q , j = 7 . 1 hz ), 2 . 6 - 2 . 7 ( 3h , m ), 3 . 1 - 3 . 3 ( 2h , m ), 3 . 38 ( 1h , d , j = 13 . 6 hz ), 3 . 50 ( 1h , d , j = 13 . 6 hz ), 4 . 0 - 4 . 1 ( 1 h , m ), 6 . 5 - 6 . 6 ( 1h , m ); anal . calcd . for c 18 h 28 n 2 o 3 s : c , 61 . 33 ; h , 8 . 01 ; n , 7 . 95 . found : c , 61 . 48 ; h , 8 . 02 ; n , 7 . 98 . the crystalline form of this material varied depending on how fast it precipitated out of hexane and the concentration during the purification step . 1 , 4 - adduct ( 1 )- 14 derived from ( 1 )- 13 . to a solution of enoyl sultam ( 1 )- 13 ( 5 . 6 g , 16 . 0 mmol ) in toluene ( 200 ml ) at − 78 ° c . was added p - tolylmagnesium bromide ( 33 . 6 mmol , 33 . 6 ml of a 1 . 0m solution in ether ) over 10 min . after being stirred an additional 30 min at − 78 ° c ., the reaction mixture was placed in a freezer (− 10 ° c .) overnight and then warmed to + 5 ° c . for two additional hours . the mixture was quenched by adding it to saturated nh 4 cl ( 200 ml ). after extraction of the aqueous layer with ether ( 400 ml ), the ether layer was extracted with 3 % hcl ( 3 × 200 ml ). the acidic layers were combined , made basic with conc . nh 4 oh ( ph = 12 ), extracted with ether ( 3 × 200 ml ), and the ether layers were washed with brine , dried ( mgso 4 ), filtered , and concentrated under reduced pressure to give an orange solid ( 7 . 12 g ). this solid was recrystallized from ether - hexane ( ca . 40 ml of an approximately 1 : 2 mixture , respectively ). yield = 3 . 64 g . a second crop gave another 1 . 24 g . total = 4 . 68 g ( 66 %). m . p .= 150 . 5 - 151 . 7 ° c . ( ether - hexane ; dense , thick , straw - colored prisms ); [ α ] d 21 = 26 . 2 ° ( c = 1 . 14 , chcl 3 ); 1 h nmr ( 500 mhz , cdcl 3 ); δ0 . 44 ( 3h , s ), 0 . 82 ( 3h , s ), 1 . 13 ( 3h , t , j = 7 . 16 hz ), 1 . 20 - 1 . 30 ( 2h , m ), 1 . 40 - 1 . 55 ( 1h , m ), 1 . 62 - 1 . 65 ( 1h , m ), 1 . 70 - 1 . 85 ( 3h , m ), 1 . 95 - 2 . 05 ( 1h , m ), 2 . 05 - 2 . 10 ( 1h , m ), 2 . 27 ( 3h , s ), 2 . 55 ( 2h , q , j = 7 . 16 hz ), 2 . 55 - 2 . 62 ( 1h , m ), 2 . 68 - 2 . 72 ( 1h , m ), 2 . 82 ( 1h , dd , j = 10 . 64 , 3 . 47 hz ), 3 . 12 ( 1h , t , j = 10 . 8 hz ), 3 . 24 - 3 . 28 ( 1h , m ), 3 . 30 ( 1h , d , j = 14 . 0 hz ), 3 . 32 ( 1h , d , j = 14 . 0 hz ), 3 . 55 - 3 . 60 ( 1h , m ), 3 . 67 - 3 . 71 ( 1h , m ), 7 . 02 ( 2h , d , j = 7 . 96 hz ), 7 . 15 ( 2h , d , j = 7 . 96 hz ); anal . calcd . for c 25 h 36 n 2 o 3 s : c , 67 . 53 ; h , 8 . 16 ; n , 6 . 30 . found : c , 67 . 58 ; h , 8 . 15 ; n , 6 . 30 . enantiomerically pure ketone ( d )- 7 derived from ( 1 )- 14 . to a solution of the 1 , 4 - adduct ( 1 )- 14 ( 6 . 86 g , 15 . 45 mmol ) in thf ( 40 ml ) was added to a freshly prepared solution of lioh . multidot . h 2 o ( 6 . 43 g , 153 mmol ) in water ( 40 ml ). the resulting heterogeneous mixture was vigorously stirred at a gentle reflux for 26 h . the mixture was cooled to ca .+ 5 ° c ., acidified to ph = 0 with conc . hcl , and the bulk of the volatile components were removed by directing a moderately strong current of nitrogen gas over the surface of the mixture while it was immersed in a warm water bath ( temp = 50 ° c .). the remaining solid was thoroughly dried under high vacuum . the crude material obtained was cyclized to ketone ( d )- 7 in a manner similar to racemic material ( see above ) using thionyl chloride and then alcl 3 in 1 , 2 - dichloroethane . this yielded 1 . 12 g of free base ketone ( d )- 7 as an oil which solidified upon standing overnight . a portion of this material was purified after being recovered from the next step in order to get physical data . [ α ] d 20 =+ 95 . 9 ° ( free base , c = 1 . 2 , chcl 3 ); [ α ] d 20 =+ 71 . 9 ° ( hcl salt , c = 1 . 1 , chcl 3 ). enantiomerically pure olefin ( d )- 15 derived from ketone ( d )- 7 . this material was obtained from ketone ( d )- 7 ( 1 . 12 g , 4 . 89 mmol ) in a manner similar to the racemic procedure ( see u . s . pat . no . 5 , 319 , 084 ). the yield was 850 mg ( 47 %). [ α ] d 19 =+ 21 . 2 ° ( c = 1 . 24 , chcl 3 ). the synthesis of ( 1 )- 2 - ethyl - 7 - methyl - 2 , 3 , 4 , 4a , 5 , 9b - hexahydro - 5 -( 4 - bromophenyl )- 5 - hydroxy - 1 h - indeno [ 1 , 2 - c ] pyridine . to a vigorously stirred solution of 4 - bromoiodobenzene ( 13 . 8 g , 48 . 9 mmol ) in 160 ml thf at − 78 ° c . was added n - butyllithium solution ( 19 . 6 ml , 2 . 5 m in pentane , 49 mmol ) very slowly . after the addition , the solution was stirred at − 78 ° c . for 10 min . the solution became yellow and cloudy . a solution of ( d )- 2 - ethyl - 7 - methyl - 1 , 2 , 3 , 4 , 4a , 5 , 9b - hexahydroindeno [ 1 , 2 - c ] pyridin - 5 - one ( 8 g , 34 . 9 mm ) in 40 ml thf was added . the mixture was then stirred at − 78 ° c . for 2 h . the cooling bath was removed and the mixture was quenched with water . the organic phase was separated and the aqueous phase was extracted with methylene chloride . the organic phases were combined , washed with brine and dried over mgso 4 . evaporation of the solvent afforded the crude product , which was recrystallized from methylene chloride to produce the title compound ( 10 . 8 g , 80 %). m . p ., 169 . 6 - 170 . 3 ° c . 1 h nmr ( 250 mhz , cdcl 3 ), δ1 . 00 ( 3h , t , j = 7 . 3 hz ), 1 . 70 - 2 . 00 ( 2h , m ), 2 . 15 - 2 . 30 ( 1h , m ), 2 . 29 ( 3h , s ), 2 . 38 ( 2h , q , j = 7 . 3 hz ), 2 . 5 - 2 . 7 ( 2h , m ), 2 . 70 - 2 . 85 ( 1h , m ), 2 . 85 - 3 . 00 ( 1h , m ), 3 . 30 - 3 . 50 ( 1h , m ), 6 . 84 ( 1h , s ), 7 . 17 ( 2h , q , j = 7 . 5 hz ), 7 . 31 ( 2h , d , j = 11 hz ), 7 . 43 ( 2h , d , j = 11 hz ). ms : 386 ( m ), 230 ( 100 %). [ α ] d =− 11 . 5 ° ( c = 1 . 03 , chcl 3 ). anal . ( c 22 h 24 obrn ): calculated c , 65 . 28 , h 6 . 26 , n 3 . 62 ; found c 65 . 11 , h 6 . 21 , n 3 . 64 . the synthesis of the ( 1 )- enantiomer of ( 4asr , 5rs , 9bsr )- 2 - ethyl - 7 - methyl - 2 , 3 , 4 , 4a , 5 , 9b - hexahydro - 5 -( 4 - bromophenyl )- 1h - indeno [ 1 , 2 - c ] pyridine ( 1 ). a solution of ( 1 )- 10 - 2 - ethyl - 7 - methyl - 2 , 3 , 4 , 4a , 5 , 9b - hexahydro - 5 -( 4 - bromophenyl )- 5 - hydroxy - 1h - indeno [ 1 , 2 - c ] pyridine ( 4 , 5 g , 13 mmol ) and 100 ml triethylsilane in 300 ml anhydrous methylene chloride was cooled to − 78 ° c . trifluoroborane gas was bubbled to the solution for 10 min . the colorless solution turned to orange . the mixture was warmed to room temperature and 10 g potassium carbonate was added , followed by water . the organic phase was separated and the aqueous phase was extracted with methylene chloride . the organic phases were combined , washed with brine and dried over mgso 4 . the solvent was evaporated to give the crude product . the crude product was dissolved in 40 ml n - butanol . potassium hydroxide ( 9 g ) was added . the mixture was heated to reflux with stirring . after being refluxed for 20 h , the mixture was cooled to room temperature and poured into ice . the mixture was extracted with methylene chloride . the methylene chloride solution was washed with brine and dried over mgso 4 . the solvent was evaporated and the crude product was partitioned between diethyl ether and 18 % hydrochloric acid solution . layers were separated and the aqueous solution was washed one more time with diethyl ether . the aqueous solution was cooled to 0 ° c . and basified with 50 % sodium hydroxide solution to ph & gt ; 14 . the mixture was extracted with methylene chloride three times . the organic solution was washed with brine and dried over mgso 4 . evaporation of the solvent afforded the crude product , which was purified with flash column chromatography ( silica gel , ch 2 cl 2 and meoh , 100 : 3 ) to give the title compound ( 1 )- 10 , 3 . 2 g , 67 % yield ( over two steps ). the hydrochloride salt was made in the usual manner . m . p . 240 ° c . ( decompose ). 1 h nmr ( 250 mhz , cdcl 3 ), δ1 . 12 ( 3h , t , j = 7 . 25 ), 1 . 6 - 1 . 8 ( 1h , m ), 1 . 80 - 2 . 05 ( 2h , m ), 2 . 15 - 2 . 40 ( 2h , m ), 2 . 26 ( 3h , s ), 2 . 70 - 2 . 85 ( 1h , m ), 2 . 90 - 3 . 10 ( 1h , m ), 3 . 30 - 3 . 45 ( 1h , m ), 4 . 12 ( 1h , d , j = 10 . 25 hz ), 6 . 72 ( 1h , s ), 7 . 00 - 7 . 30 ( 4h , m ), 7 . 44 ( 2h , d , j = 9 . 0 hz ). ms : 370 ( m ). [ α ] d =− 7 . 8 ° ( c = 0 . 83 , meoh ). anal . ( c 21 h 24 brnhcl ): calculated c 62 . 00 , h 6 . 19 , n 3 . 44 ; found c 61 . 96 , h 6 . 23 , n 3 . 35 . the synthesis of ( 1 )- enantiomer of ( 4ars , 5sr , 9brs )- 2 - ethyl - 2 , 3 , 4 , 4a , 5 , 9b - hexahydro - 7 - methyl - 5 -( 4 - carboxyphenyl )- 1h - indeno [ 1 , 2 - c ] pyridine hydrochloride [( 1 )- 2 ]. a solution of 100 mg ( 0 . 27 mmol ) of ( 1 )- 10 compound in 5 ml thf was cooled to − 78 ° c . to this solution was added 0 . 54 ml n - butyllithium solution ( 2 . 5 m in pentane , 1 . 35 mmol ). the solution was stirred at − 78 ° c . for 30 min . carbon dioxide gas was bubbled into the solution for 10 min through a needle . the mixture was stirred at − 78 ° c . for 10 more minutes and warmed to room temperature . thf was evaporated and the residue was acidified with 18 % hydrochloric acid . the mixture was extracted with methylene chloride . the methylene chloride solution was washed with brine and dried over mgso 4 . the drying reagent was filtered and the solution was concentrated to give the crude product . column chromatography ( silica gel , ch 2 cl 2 and meoh , 10 : 1 to 1 : 1 ) of the crude product afforded 72 mg ( 71 % yield ) (−)- 2 . [ α ] d =− 15 . 5 ° ( c = 1 . 24 , meoh ). synthesis of the ( d )- enantiomer of ( 4ars , 5sr , 9brs )- 2 - ethyl - 2 , 3 , 4 , 4a , 5 , 9b - hexahydro - 7 - methyl - 5 -( 4 - carbomethoxyphenyl )- 1h - indeno [ 1 , 2 - c ] pyridine hydrochloride [( d )- 3 ]. a solution of ( 1 )- 2 ( 20 mg ) in 1 ml methanol was cooled to − 10 ° c . ( ice - acetone ). excess thionyl chloride was added . after the addition , the mixture was warmed to room temperature and stirred overnight . excess thionyl chloride and the solvent were blown away with nitrogen and the residue was dried under vacuum . the crude product was analyzed with hplc ( sumichiral , qa - 4900 , 4 mm × 25 cm ; solvents : 53 . 8 % 1 , 2 - dichloroethane , 44 % hexane , 2 . 2 % ethanol , and 0 . 1 % tfa ; flow rate : 0 . 8 ml / min ; λ = 254 nm ), which showed & gt ; 97 % ee of ( d )- 3 . synthesis of the ( d )- enantiomer of ( 4ars , 5sr , 9brs )- 2ethyl - 2 , 3 , 4 , 4a , 5 , 9b - hexahydro - 7 - methyl - 5 -( 4 - carboxyphenyl )- 1h - indeno [ 1 , 2 - c ] pyridine hydrochloride [( d )- 2 ] and of the ( 1 )- enantiomer of ( 4ars , 5sr , 9brs )- 2 - ethyl - 2 , 3 , 4 , 4a , 5 , 9b - hexahydro - 7 - methyl - 5 -( 4 - carbomethoxy phenyl )- 1h - indeno [ 1 , 2 - c ] pyridine hydrochloride [( 1 )- 3 ]. these two compounds may be synthesized by starting with enoylsultam ( d )- 13 described above and carrying out the subsequent steps above used for the synthesis of their enantiomers . their properties have been previously described . see cook et al ., j . med . chem ., 38 : 753 - 763 ( 1995 ). obviously , numerous modifications and variations of the present invention are possible in light of the above teachings . it is therefore to be understood that , within the scope of the appended claims , the invention may be practiced otherwise than as specifically described herein
hexahydroindenopyridine compounds are provided which act as spermicides and / or fungicides , spermicidal and / or fungicidal compositions containing the same , and methods for killing motile sperm and / or fungi using the compounds and compositions .