Synthesis and conformational study of P‐heterocyclic androst‐5‐ene derivatives

摘要: The reactions of (20R)-3β-acetoxy-21-hydroxymethylpregn-5-en-20-ol (2) and (20R)-3β-acetoxypregn-5-ene-20,21-diol (11) with phenylphosphonic dichloride 3 aryl dichlorophosphates 4–6 afforded novel types P-heterocyclic androst-5-ene derivatives 7–10 12 as epimeric pairs. diastereomers were separated by column chromatography characterized NMR spectroscopy. Estimation the stereostructures corresponding epimers B3LYP/631G(d) DFT ab initio calculations suggested that six-membered hetero ring in compounds 7b 8a–10a adopts predominantly a chair conformation, P-substituents their preferred orientation. cyclic phosphonate moiety 7a or 8b–10b, however, seems to exist an equilibrium mixture chair–distorted-boat chair–chair forms. theoretical indicate conformational is shifted toward distorted-boat conformer for 7a, pseudoequatorial P-phenyl substituent, whereas 8b–10b equatorial P-phenoxy group predominates. © 2008 Wiley Periodicals, Inc. Heteroatom Chem 19:7–14, 2008; Published online InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20372