Leland Stanford Junior University

The Coca-cola Company

The Nutrasweet Company

Grant E Dubois

Indra Prakash

George A King

Rafael I San Miguel

Kelly H Sepcic

Deepthi K Weerasinghe

Prashanthi Jella

George W Muller

Jeffery S Carter

Darold L Madigan

Rafael Ignacio San Miguel

William S Johnson

Russell C Klix

David J Ager

Mani Upreti

John Clos

Sina Escher

Newton R White

Rudy J Fritsch

D Eric Walters

John C Culberson

Srivivasan Nagarajan

Carrie A Klade

Anish Mehta

Method is provided for cyclization of polyunsaturated substituted acylic or monocarbocyclic initiator group containing compound having an endocyclic double bond with a chalcogen atom in the allylic position of the initiator group and having at least two sites of unconjugated aliphatic unsaturation in the side chain substituent on the ring. The polyunsaturated compound is cyclized in the presence of a strong acid in a protic solvent which is inert to the acid, preferably a hydroxylic solvent. Mild temperatures and varying times are employed. The products are useful primarily as intermediates for naturally occurring and synthetic steroids. By appropriate substitution of the side chain, the steroidial products are provided with the substituent at C-11, which upon cyclization results in the alpha-configuration. By resolution of the intermediates prior to cyclization, optically active steroids can be obtained.

A-Norsteroids

Compositions are provided as well as methods for preparing the compositions which serve as cyclization precursors for the preparation of C-11 alkenyl substituted steroids and nor-steroids. The alkenyl group may be converted after cyclization to a variety of heterosubstituents to provide heterofunctionalized C-11 steroids and nor-steroids. The compounds are provided having an initiator group, which has a chalcoxy atom in juxtaposition to a double bond, an olefinically unsaturated linking group and a terminating group which acts to from a carbocation which reacts with a nucleophile to provide a stable product. The C-11 substituent is found to provide upon cyclization the alpha-configuration, so that the subject compounds provide a direct route to the difficultly accessible alpha-C-11 substituted steroids, or, if desired, the alpha-configuration can be inverted to the beta-configuration.

Olefinically unsaturated substituents at C-11 of steroid cyclization

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Menlo Park, CA, United States of America

Grant E Dubois