94 リファマイシンWの全合成(口頭発表の部)

概要

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Rifamycin W (1) was isolated from a mutant strain of Nocardia mediterranei and is thought to be the biosynthetic intermediate of all the rifamycins. The configurations of the C28 position and the C12 - C29 double bond in 1 were so far unknown. We now report the first total synthesis of rifamycin W (1) and elucidate the whole stereochemistry of 1. We assumed conveniently the C28-hydroxylmethyl configuration in 1 to be R by considering the facility of the synthesis. The selected ansa-chain aldehyde 4, corresponding to the C17 - C29 portion of 1, was enantiospecifically synthesized from levoglucosan (3) by using our developed "two-stage coupling process" as a key step. The zinc enolate of the aromatic chromophore 5 was subjected to the coupling with the aldehyde 4 to give the coupling products 31a and 31b. Both the separated products were independently dehydrated to afford the same E-olefin 32 as a mixture of atropisomers. 32 was transformed to the amine-carboxylic acid 37 which was cyclized under the Baker's conditions [bis(2-oxo-3-oxazolidinyl)phosphinic chloride, i-Pr_2NEt] to afford 38. Oxidative de-O-methylation and subsequent deprotection of 38 gave rifamycin W (1), which was identical with natural rifamycin W in all respects. This goal indicates that the configurations of the C28 position and the C12 - C29 double bond are R and E, respectively.
天然有機化合物討論会の論文
1990-09-25