1. Field of the Invention
The perhydrocyclopentanophenanthrenes are a widely occurring group of natural substances referred to as steroids. The basic carbon skeleton is retained, with the various steroids differing primarily in the substituents bonded to the annular atoms and the degree and sites of unsaturation. Depending upon the nature of the substituents, the steroids fulfill a great diversity of functions in both animals and vegetables.
To a great degree, synthetic work in the field of steroids has been dependent upon a source of the intact polycyclic structure, which would then be modified by the introduction, removal or modification of substituents which are present, the introduction or extension of carbon chains, or the like.
The reliance on naturally occurring materials as the substrate for production of commercially useful steroids has many drawbacks. Introduction of a functionality at a particular site may be achieved only with difficulty, where there is no convenient functionality at or near the site of interest. Fluctuations in availability which depend upon the weather, government agencies or the like can make supplies unreliable. Having to rely on naturally occurring materials reduces the flexibility in being able to introduce new substituents at a variety of sites on the carbocyclic nucleus.
It is, therefore, desirable to be able to synthesize from relatively simple and accessible compounds the steroid nucleus, whereby the substituents are present in the precursor molecules or are introduced by modification of functionalities which are present in the precursor molecules. The synthesis must take into account a number of factors. The steroid nucleus has a specific geometry, so that the synthesis must provide a product which has the desired geometry or one which can be readily modified to achieve the desired geometry. In addition, the product will normally have one or more stereoisomeric sites. Conveniently, the synthesis may allow for resolution of an intermediate, so as to provide for the desired stereoisomer as the final product. Where there is more than one stereoisomeric site, it is desirable that there be asymmetric induction by the stereoisomeric substrate employed in the cyclization process. In addition, each of the steps must anticipate the reagent needs of future steps, so that one minimizes the need for introduction and removal of protective groups, modification of functional groups, and the like. Also, the synthetic procedure must allow for cyclization to the desired product without forming complex mixtures which allow for only difficult isolation of the desired product.
In cyclizing polyenes to polycyclic products, substituents can have both electronic and steric effects. The rather loose aliphatic chain is confined to a rigid orientation as the steroid structure is formed. Substituents may therefore have non-bonded interactions which may impede cyclization. Where heteroatoms are present, these may indirectly affect the cyclization, particularly where they are subject to protonation. In addition, some substituents, e.g. olefins, could become involved in the cyclization resulting in undesired side products.
2. Description of the Prior Art
Cyclization of monocyclic polyunsaturated compounds has been reported in a number of articles as well as patents. U.S. Pat. Nos. 3,558,672 and 3,598,845 report cyclization of different precursors to the perhydrocyclopentanophenanthrene structure. Scientific articles of interest include Johnson, et al., J. Am. Chem. Soc., 90, 2991 (1968); ibid, 92, 741 (1970); and ibid, 93, 4432 (1971).
USPTO Backgrounds
USPTO Backgrounds