Steroid Total Synthesis, Part II; (−)-17β-Hydroxy-des-A-androst-9-en-5-one

✍ Scribed by G. Saucy; R. Borer

• Publisher: John Wiley and Sons
• Year: 1971
• Tongue: German
• Weight: 848 KB
• Volume: 54
• Category: Article
• ISSN: 0018-019X
• DOI: 10.1002/hlca.19710540746

✦ Synopsis

Based on the results obtained in the raceniic series (part I ) , ( -)-17P-hydroxy-des-A-androst-9-en-5-one has been synthesized, starting with (S)-( -)-5-heptanolide. The key step, viz. the condensation of ( S ) -( -)-7-hydroxy-l-nonen-3-one (or its amine adduct) with 2-methyl-cycIopentane-l,3-dione involves an asymmetric induction. Model experiments with (R)-( + )-5decanolide leading to the enantiomeric homolog of the BCD-tricyclic compound are also described.

Recently we described [l] a new and efficient total synthesis of racemic 178hydroxy-des-A-androst-9-en-5-one. The present report deals with the synthesis of its optically active form3). The stereoselective synth-sis involves a novel asymmetric induction step which we encountered [l] in the racemic series.

Stereochemistry of the key intermediate. In our work [l] with racemic material, we

were not able to determine unambiguously the stereochemistry (2 or 3 ?) of the major product obtained from 2-methylcyclopentane-1,S-dione and the vinyl ketone 1 (reflux in pyridine-toluene). The problem was readily solved by carrying out an analogous sequence (see scheme 1) comprising as the key step the condensation of the optically active vinyl 8-hydroxy-ketone 7 with 2-methylcyclopentane-1,3-dione to afford the l) Part I, cf. [l].