The total synthesis of the oxopolyene macrolide RK-397.
The total synthesis of the oxopolyene macrolide RK-397.
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氧代多烯大环内酯RK-397的全合成。
DOI：
10.1002/anie.200602601
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
Sammakia,Tarek
中科院分区：
文献类型：
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作者：
Mitton-Fry,MarkJ;Cullen,AaronJ;Sammakia,Tarek
立体化学复杂的天然产物RK-397（1，方案1）于1993年从土壤细菌菌株中分离，并且显示具有抗真菌、抗肿瘤和抗细菌活性。[1]RK-397是一种氧代多烯大环内酯[2]，其结构[3]对应于C14-去甲基真菌霉素A [4]，其中C19和C21的立体中心具有相反的构型。[5]这类天然产物的成员是合成的流行目标，[6]和Burova和McDonald [7]以及丹麦和Fujimori [8]最近报道了RK-397的合成。在此，我们描述了我们最近完成的路线，这个分子提出了几个合成的挑战，包括立体化学复杂的多元醇链的有效建设，敏感的多烯部分的引入，和大环的形成。与以前的氧代多烯大环内酯合成类似，我们计划通过大环内酯化形成大环。[9]多元醇被断开成两个具有大致相等复杂性的片段，即甲基酮2（C22-C33）和醛3（C10-C21，方案1）。我们设想了一种不对称催化方法，通过烯烃的立体化学接力来合成2，一种双向的
The stereochemically complex natural product RK-397 (1, Scheme 1) was isolated in 1993 from a strain of soil bacteria and was shown to possess antifungal, antitumor, and antibacterial activities.[1] RK-397 is an oxopolyene macrolide [2] whose structure [3] corresponds to that of C14-demethyl mycoticin A,[4] in which the stereocenters at C19 and C21 have the opposite configuration.[5] Members of this class of natural products have been popular targets for synthesis,[6] and Burova and McDonald,[7] as well as Denmark and Fujimori [8] have recently reported syntheses of RK-397. Herein, we describe our recently completed route to this molecule.This molecule presents several synthetic challenges, including the efficient construction of the stereochemically complex polyol chain, the introduction of the sensitive polyene moiety, and the formation of the macrocycle. In analogy to previous oxopolyene macrolide syntheses, we planned to form the macrocycle through a macrolactonization.[9] The polyol was disconnected into two fragments of roughly equal complexity, namely methyl ketone 2 (C22–C33) and aldehyde 3 (C10–C21, Scheme1). We envisioned an asymmetric catalysis approach with relay of stereochemistry across the alkene for the synthesis of 2, a two-directional