1,4-Dioxepan-5-one of the formula (III): ##STR3## which corresponds to the basic skeleton of the compound of the present invention, is known (although the compound of formula (III) can also be named 1,5-dioxepan-2-one, only the former nomenclature is used throughout the specification and appended claims).
For example, British Patent 1,272,733 discloses a process comprising reacting ethylene glycol with acrylonitrile in the presence of 50% sodium hydroxide to obtain 2-(2-cyano ethoxy)ethanol and cyclizing this compound by passing dry hydrogen chloride therethrough in methylene chloride to prepare 5-imino-1,4-dioxepan-5-one hydrochloride, which is then heated in an aqueous solution at 40.degree. C. to obtain 1,4-dioxepan-5-one (total yield: about 5%).
U.S. Pat. No. 4,470,416 discloses a process comprising reacting ethylene glycol with methyl acrylate in the presence of NaOMe (wherein Me is a methyl group, hereinafter the same) to prepare methyl 3-(2-hydroxyethoxy)propionate and converting this compound into 1,4-dioxepan-5-one using (i-PrO).sub.4 Ti (wherein i-Pr is an isopropyl group) as a catalyst (total yield: about 17%). Further, Macromolecules, Vol. 22, 3832-3846 (1989) describes a process comprising reacting .beta.-chloropropionyl chloride and ethylene in the presence of an AlCl.sub.3 catalyst to prepare 1,5-dichloropentan-3-one and cyclizing this compound upon heating at 100.degree. C. in the presence of H.sub.3 PO.sub.4 /NaH.sub.2 PO.sub.4 to obtain 4-ketotetrahydropyran, which is then oxidized with 3-chloroperbenzoic acid to obtain 1,4-dioxepan-5-one (total yield: about 48%).
With respect to polymers of 1,4-dioxepan-5-one, the above cited U.S. Pat. No. 4,470,416 discloses that a copolymer of 1,4-dioxepan-5-one and lactide and/or glycolide is synthesized by use of tin caprylate and that the thus obtained polymer can be formed into fibers and used as a surgical suture and in other applications. U.S. Pat. No. 4,190,720 discloses a process for synthesizing a copolymer consisting of a large proportion of .epsilon.-caprolactone and a small proportion of 1,4-dioxepan-5-one in the presence of tin caprylate. However, any of the synthesis processes of 1,4-dioxepan-5-one disclosed in the above-cited patents is defective in that the yield is low. Further, these known processes are also disadvantageous in that polymers of the compound which can be produced are limited to copolymers and that since the monomer has no substituent group at the 7-position, the copolymers are not optically active and insufficient in biodegradability and, in particular, biocompatibility.
On the other hand, microorganisms which accumulate therein polymers of a 3-hydroxyalkanoic acid corresponding to a part of the constitutent components of the ring in the compound of the present invention have become known recently (see P. A. Holmes, Phys. Technol, 16, 32 (1985)). Since these polymers have advantageous properties such as biodegradability or enzymatic degradability, hydrolyzability, and biocompatibility, they are attracting attention as a new type of functional material (see Seibunkaisei Kobunshi Zairyo, p. 19, edited and written by Yoshiharu Doi, published by Kogyo ChosaKai, Japan, 1990). Further, ring opening polymerization of D-(+)-.beta.-methyl-.beta.-propiolactone is reported in Polymer Letters, 9, 173 (1970). However, since the above-described microbiological method utilizes a microorganism or an enzymatic reaction, it has various problems, such as the necessity of complicated steps, e.g., a step of separating the polymer from the microorganism and a step for optical resolution, and high production cost, leading to obstructing the commercial production thereof.
USPTO Backgrounds
USPTO Backgrounds