Stereoselective Synthesis of Moenocinol and Assignment of Its Carbon-13 Nuclear Magnetic Resonance Spectrum

Article abstract of DOI:10.1021/jo01301a028

A stereoselective synthesis of moenocinol (1), the sesquiterpene alcohol liberated by hydrolysis of the antibiotic moenomycin, is described.Alkylation of isobutyric acid dianion with 5-bromo-1-pentene followed by reduction with lithium aluminum hydride and benzylation provided 1-benzyloxy-2,2-dimethyl-6-heptene (4).Hydrolysis and cleavage of the epoxide of 4 with periodic acid gave 6-benzyloxy-5,5-dimethylhexanal (6). 2-Phenylthio-6-benzyloxy-5,5-dimethylhexanoic acid (8a) was prepared from 6 by chromic acid oxidation and α-phenylsulfenylation.Reaction of the dianion of 8a with geranyl bromide followed by esterification and hydride red uction afforded phenylthio alcohol 10a.Simultaneous reductive elimination and debenzylation of the corresponding acetate (10b) with lithium in ammonia gave (E)-2,2,8,12-tetramethyl-5-methylene-7,11-tridecadien-1-ol (11). (Z)-1-Benzyloxy-6-bromo-3-methyl-4-hexene (17b) was prepared from the benzyl ether of nerol by the following four steps: regioselective ozonolysis, borohydride reduction, formation of the tosylate and displacement with bromide ion.The reaction of the Grignard reagent from 17b with the aldehyde (12) secured by oxidation of 11 afforded an alcohol which was oxidized to (2Z,13E)-1-benzyloxy-3,8,8,14,18-pentamethyl-11-methylene-2,13,17-nonadecatrien-7-one (33).The 6,7-trans (Z) enol phosphate 34, formed by phosphorylation of the enolate anion of 33, underwent reduction with lithium in ammonia to (2Z,6E,13E)-3,8,8,14,18-pentamethyl-11-methylene-2,6,13,17-nonadecatetraen-1-ol (1) which was identical with moenocinol obtained from moenomycin.The 6,7-cis isomer (32b) of moenocinol was also prepared by a Wittig reaction between aldehyde 12 and phosphorane 18 and subsequent reductive debenzylation.Carbon-13 NMR spectral data for synthetic and natural moenocinol compared favorably; a consistent set of assignments for the 13C NMR absorptions is deduced from comparisons with model compounds.