Total synthesis of erythronolide A

Masaya Nakata, Masayuki Arai, Katsuhiko Tomooka, Naoki Ohsawa, Mitsuhiro Kinoshita

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

The enantiospecific total synthesis of erythronolide A (1) through (9S)-9-deoxo-9-hydroxyerythronolide A (2) from the chiral CI C6, C7C9, and CIOC13 synthetic segments is described. The CIOC13 segment, (3K,4R,53R)-5-0-benzyl-2-iodo-3,4-0-isopropylidene-4-methyl-l-heptene-3,4,5-triol (11) was synthesized in 16 steps and an 8.3% overall yield from D-ribose. The C7C9 segment, (S)-(+)-2-(2-bromo-l-methylethyl)-l,3-dioxolane (47) was prepared from methyl (S)-(+)-3-hydroxy-2-methylpropionate in 8 steps and a 49% overall yield. The coupling of the Grignard reagent, prepared from magnesium and 47, and the CIC6 segment, 3,5,7-tri-0-benzyl-l,4,6-trideoxy-4,6-di-C-methyl-Aeo-L-zVio-2-heptulose (13), afforded 5,7,9-tri-O-benzyl-2,3,6,8-tetradeoxy-2,4,6,8-tetra-C-methyl-L-/zreo-L-Z(io-nonose ethylene acetal (48) and its C4-epimer in 79% and 8% yields, respectively. 5,7,9-Tri-0-benzyl-4-0-butyldimethylsilyl-2,3,6,8-tetradeoxy-2,4,6,8-tetra-C-methyl-L-threo-L-ido-nonose (12), derived from 48, was subjected to coupling reaction with the lithium reagent prepared from 11 to afford about 5 :1 excess of the "Cram" product 50. The homogeneous hydrogenation of 50 with [ClRh(Ph3P)2] gave l,3,5,13-tetra-O-benzyl-6-O-butyldimethylsilyl-2,4,7,8,10,14,15-heptadeoxy-ll,12-O-isopropylidene-2,4,6,8,10,12-hexa-C-methyl-D-ara6mo-D-g/wco-L-zd!o-pentadecitol (54) and its ClO-epimer in 41% and 7% yields from 12, respectively. The conversion of 54 to 2 was accomplished by a sequence of reactions including the Corey-Nicolaou lactonization method in a 17% overall yield. Selective 3,5-O-benzylidenation of 2 followed by PCC oxidation and debenzylidenation gave 1 in 52% yield.

Original languageEnglish
Pages (from-to)2618-2635
Number of pages18
JournalBulletin of the Chemical Society of Japan
Volume62
Issue number8
DOIs
Publication statusPublished - 1989 Aug

ASJC Scopus subject areas

  • Chemistry(all)

Fingerprint Dive into the research topics of 'Total synthesis of erythronolide A'. Together they form a unique fingerprint.

  • Cite this

    Nakata, M., Arai, M., Tomooka, K., Ohsawa, N., & Kinoshita, M. (1989). Total synthesis of erythronolide A. Bulletin of the Chemical Society of Japan, 62(8), 2618-2635. https://doi.org/10.1246/bcsj.62.2618