A radical prototype to steroids: Synthesis of d,l-5α-D-homoandrostane-4α-methyl-3,17a-dione

The biosynthesis of steroids and triterpenoids

“…Model reaction studies have indicated that neither of these difficulties are insuperable, however, given careful substrate design. [372][373][374] A number of radical-initiated biomimetic cyclizations of polyene SO analogues have been described [375][376][377] in one of which the steroid nucleus (rings A-D) is formed cleanly, albeit as a mixture of isomers at the 17-position (steroid numbering), and with 9,10-anti stereochemistry (see above). 378,379 Investigation of cationic biomimetic cyclizations of SO analogues has resulted in some successes in forming pentacyclic triterpene skeletons (all with a 9,10-anti ring junction), but not the steroid nucleus.…”

Recent developments in the isolation and synthesis of D-homosteroids and related compounds

“…The first intermolecular Pd-catalyzed reaction led in a highly regio-and diastereoselective way to 73, which afforded 74 with an unnatural B/C cis-junction in a second intramolecular Heck reaction (Scheme 18). 57 New, biomimetic, intramolecular methodology for the preparation of racemic Dhomosteroids has been described by Zoretic et al 58 The polyene 77 has been cyclized to the tetracycle 78 in a radical process. After removal of the ethoxycarbonyl functional group on C-4 and conversion of the angular cyano group on C-8 into β-H, 4-methyl-D-homoandrostanolone 79 was obtained (Scheme 19).…”

Application of a Radical Methodology toward the Synthesis of d,l-5α-Pregnanes and Related Steroids: A Stereoselective Radical Cascade Approach

“…A stereoselective one-step entry to tetracylic products , via a radical cascade cyclization , of polyenic substrates can now be achieved in favorable yields. Our laboratory has demonstrated that these tandem cyclizations can be used to introduce from five to seven stereogenic centers in a highly predictable manner in various polycyclic systems. , It has also been shown that a radical approach can be utilized in the synthesis of a methylated D-homosteroid . To extend this radical methodology to natural steroids, two modifications of the polyene have to be addressed based on our earlier model.…”