Synthetic approach to potential precursors of sclerophytin A
Synthetic approach to potential precursors of sclerophytin A
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DOI：
10.1016/s0040-4020(03)00283-7
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发表时间：
2003-04-07
期刊：
影响因子：
2.1
通讯作者：
Pontillo, J
中科院分区：
文献类型：
--
作者：
Jung, ME;Pontillo, J
本文介绍了一种直接合成抗肿瘤天然二萜硬植素A的简单双环类似物的方法。将容易获得的双环酮8（由呋喃和三氯丙酮制备）对映选择性地甲基化以得到光学活性酮11。使用Negishi的方法进行区域选择性烯丙基化，得到α，α-二烷基酮12，通过硼氢化-氧化和保护将其转化为氯乙酸酯15。区域选择性Baeyer-Villiger氧化得到内酯7a，其可转化为甲硅烷基醚7 b。Tebbe烯化提供两种烯醇醚的混合物，其中所需产物17是次要异构体。几次尝试使用主要的内环烯醇醚18来得到硬植素的三环类似物证明是不成功的。打开18的内酯并选择性保护二醇，得到伯醇24，将其氧化为酮醛25。不幸的是，25的频哪醇偶联没有得到任何环状产物。二烯27也由25制备，但27的闭环复分解的所有尝试都遇到了相同的命运。这些各种环化方法的失败强调了形成中等大小的环系统的困难，特别是那些在四氢呋喃环的2-和5-位顺式稠合的环系统。(C)2003爱思唯尔科技有限公司版权所有。
A direct approach to simple bicyclic analogues of the antitumor natural diterpene, sclerophytin A, is described. The readily available bicyclic ketone 8 (prepared from furan and trichloroacetone) was enantioselectively methylated to give the optically active ketone 11. Regioselective allylation using Negishi's method afforded the alpha,alpha-dialkyl ketone 12, which was converted to the chloroacetate 15 by hydroboration-oxidation and protection. Regioselective Baeyer-Villiger oxidation afforded the lactone 7a which could be transformed into the silyl ether 7b. Tebbe olefination furnished a mixture of two enol ethers in which the desired product 17 was the minor isomer. Several attempts to use the major endocyclic enol ether 18 to give the tricyclic analogues of sclerophytin proved unsuccessful. Opening of the lactone of 18 and selective protection of the diol afforded the primary alcohol 24 which was oxidized to the keto aldehyde 25. Unfortunately pinacol coupling of 25 did not give any cyclic product. The diene 27 was also prepared from 25 but all attempts at ring-closing metathesis of 27 met with the same fate. The failure of these various cyclization methods underscores the difficulty in forming medium-sized ring systems, especially those cis-fused at the 2- and 5-positions of a tetrahydrofuran ring. (C) 2003 Elsevier Science Ltd. All rights reserved.