Alkinyl terminating groups in biogenetic-like cyclizations to steroids
AssigneeThe Board of Trustees of the Leland Stanford Junior University
InventorsWilliam S. Johnson, Michael B. Gravestock
Life of this patent
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Abstract
Polyenine compounds are provided having the naturally occurring geometry and a group which in the presence of acid initiates a carbocation cyclization to a steroid or A-nor-steroid structure, particularly the pregnane parent structure. The compounds are formed for the most part by condensation of two units prepared from readily available small molecules and are joined to form a polyenine, usually having a substituted carbocyclic ring which upon contact with a Lewis acid catalyst (includes protonic) cyclizes directly to provide the 5-membered D ring as well as substitution at the C-20 position.
Claims7
A method for preparing a cyclization product having a structure B ##STR55## from a substrate having the structure A ##STR56## the method comprising:
- contacting said substrate in a solvent with from about 1 to 50 equivalents of a Lewis acid per equivalent of said substrate at a temperature in the range of about -50 to 10.degree. C.
A method for preparing a cyclization product having a structure B ##STR57## from a substrate having the structure A ##STR58## wherein:
- a is hydrogen or lower alkyl of from 1 to 2 carbon atoms;
- R.sup.1 is hydrogen or saturated aliphatic hydrocarbon of from 1 to 3 carbon atoms and having from 0 to 1 oxy, halo or tri-(lower alkyl)silyl substituent;
- h is derived from a nucleophile selected from the group consisting of alkenes, carbocyclic aromatics, oxy, halo, nitroalkane of from 1 to 6 carbon atoms and, when the nucleophile is hydroxy is taken together with i to form oxo;
- when not taken together with h, i is taken together with j to form a double bond, and
- j, when not taken together with i, is hydrogen or when h and i are oxo and said nucleophile is nitroalkane, oximino;
- the method comprising:
- contacting said substrate in a solvent containing said nucleophile with from about 1 to 50 equivalent of a Lewis acid per equivalent of said substrate at a temperature in the range of about -50.degree. to 10.degree. C.
A method for preparing a cyclization product having a structure B ##STR59## from a substrate having the structure A ##STR60## wherein:
- a is hydrogen or lower alkyl of from 1 to 2 carbon atoms;
- R.sup.1 is hydrogen or saturated aliphatic hydrocarbon of from 1 to 3 carbon atoms and having 0 to 1 oxy, halo or tri-(lower alkyl) silyl substituent;
- e is lower alkyl of from 1 to 2 carbon atoms;
- h is derived from a nucleophile selected from the group consisting of alkenes, carbocyclic aromatics, oxy, halo, nitroalkane of from 1 to 6 carbon atoms, and, when the nucleophile is hydroxy is taken together with i to form oxo;
- when not taken together with h, i is taken together with j to form a double bond;
- and
- j when not taken together with i, is hydrogen or when h and i are oxo and said nucleophile is nitroalkane, oximino;
- the method comprising:
- contacting said substrate in an acidic halocarbon medium at a temperature in the range of about -50.degree. to 10.degree. C. with an acid at an equivalent ratio of 1-50:1 to said substrate in the presence of a nucleophile.
Dependencies are inferred from the claim text.