A Stereoselective Total Synthesis of (9S)-9-Dihydroerythronolide A via Coupling between the Right-Half (C1-C6) Aldehyde and the Left-Half (C7-C15) Sulfoxide

• Published in: Chemical & pharmaceutical bulletin Vol. 37; no. 5; pp. 1167 - 1172
• Main Authors: TONE, Hitoshi, NISHI, Takao, OIKAWA, Yuji, HIKOTA, Masataka, YONEMITSU, Osamu
• Format: Journal Article
• Language: English
• Published: Tokyo The Pharmaceutical Society of Japan 1989; Maruzen; Japan Science and Technology Agency
• Subjects: aglycone; Chemistry; erythromycin A; erythronolide A; Exact sciences and technology; Heterocyclic compounds; Heterocyclic compounds with o, s, se, te hetero atom and condensed derivatives; high dilution; macrolactonization; macrolide antibiotic; Organic chemistry; Preparations and properties; protecting group; seco-acid; stereoselective synthesis; sulfone coupling; Aldol; Stereoselectivity; Antibiotic; Silicon Organic compounds; Sulfoxide; Lactone; Polyol; Oxygen heterocycle; Macrolide; Chemical coupling; Macrocycle
• ISSN: 0009-2363; 1347-5223
• DOI: 10.1248/cpb.37.1167

As part of a study directed at the total synthesis of (9S)-9-dihydroerythronolide A, the C7-C15 sulfoxide, (2S, 3R, 4S, 5R, 6R, 7R)-3, 5-isopropylidenedioxy-7-(4-methoxybenzyloxy)-6-methoxymethoxy-1-phenylsulfinyl-2, 4, 6-trimethylnonane, was coupled with the C1-C6 aldehyde, (2R, 3S, 4S, 5R)-6-tert-butyldiphenylsilyloxy-3, 5-dimethyl-2, 4-isopropylidenedioxyhexanal, to give the C1-C15 hydroxysulfoxide, which was converted to the seco-acid via a stereocontrolled methylation at the C6 position. Macrocyclization of the seco-acid by Yamaguchi's method gave the 14-membered lactone, which was converted to (9S)-9-dihydroerythronolide A.