70(P50) 新規なγ-ラクタム型天然物・エポラクタエンの全合成研究(ポスター発表の部)

概要

論文の詳細を見る
In recent years, some highly C- and O-substituted chiral γ-lactams possessing a variety of biological activities were isolated from microorganisms. Epolactaene (1) was isolated from the culture broth of Penicillium sp. BM 1689-P by Osada et al. in 1995. This natural product shows the novel neuritogenic activities in a human neuroblastoma cell line, SH-SY5Y cells. Therefore, 1 was expected to be pharmaceutically potent on various neurodegenerative diseases including dementia. The planer structure of 1, containing an unsaturated twelve-carbon acyl side chain at the α-position of the γ-lactam ring, both hydroxy and methyl groups at the γ-position, and an epoxy ring at α,β-position, was determined by spectroscopic analysis (^1H- and ^<13>C-NMR). However, the stereochemistry of the epoxy moiety was remained to be determined. We have recently completed the first total synthesis of PI-091(2) from D-glucose-derived branched sugar derivative 3. We planed to synthesize 1 and present here our synthetic approach to 1 from 3, the starting material of the total synthesis of 2. Our synthetic strategy involves the following three key reactions: (1) an aldol reaction of an acyclic ketone 8 prepared from 3 with the lithium enolate of acetone providing a diastereomeric mixture of adducts 9, (2) transformation of 9 into a 2,4-substituted furan 10, and (3) photochemical addition of singlet oxygen to the silylated furan 12 to construct the desired γ-lactone 13. First, compound 8 was prepared via Wittig olefination of aldehyde 4, derived from 3, followed by some functional group transformations in eight steps. The aldol reaction of 8 with acetone was smoothly proceeded by using LDA as a base to give 9 as a diastereomeric mixture. In further synthetic venture, an important intermediate γ-hydroxy-γ-lactone 13 was obtained via the photosensitized singlet oxygen addition of α-silylfuran 12, which was derived from 9 via deprotection of the pivalate, acid treatment, followed by α-silylation of the resulting furan. We next pursued the construction of the triene part of the side chain in 1. For the purpose of a stepwise carbon elongation, 13 was first converted to 16 via Wittig olefination. The second step of carbon elongation of 16 and total synthesis of 1 are now in progress.
天然有機化合物討論会の論文
1997-07-20

70(P50) 新規なγ-ラクタム型天然物・エポラクタエンの全合成研究(ポスター発表の部)

スポンサーリンク

概要

著者

関連論文

スポンサーリンク