Short biomimetic synthesis of a steroid by photoinduced electron transfer and remote asymmetric induction
Short biomimetic synthesis of a steroid by photoinduced electron transfer and remote asymmetric induction
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DOI：
10.1021/ja984035z
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发表时间：
1999-05-26
影响因子：
15
通讯作者：
Demuth, M
中科院分区：
文献类型：
--
作者：
Heinemann, C;Demuth, M
光诱导电子转移(PET)1已被证明是合成单环和多环萜类骨架2的一种可行的工具，这些骨架是通过欧米伽烯位上的萜类聚烯的区域选择性氧化组装而成的。这种产生母体自由基阳离子的氧化导致(A)自由基阳离子被亲核试剂如水捕获，(B)自由基型环化(S)，以及(C)通过在环化产物的第三自由基中心的还原/质子化或通过氢原子捕获该中心来终止这种过程(方案1)。3根据聚烯基链上取代基(S)R1/2的吸电子性质，6-内切(F2)和5-外触发(F3)环的闭合终止了1的环化。这样的PET触发的级联环化被发现模仿了母体的非氧化酶过程4，这反过来又被认为是通过酶促质子化和水的反Markovnikov加成生成的阳离子中间体进行的。这种转化的一个典型例子是角鲨烯到四氢呋喃的转化。然而，后一种建议到目前为止还没有在体外得到验证。本原理基于自由基阳离子的中间体，这些阳离子是由容易获得的萜类聚烯烃以光化学方式产生的，它提供了类似自然的级联环化反应，包括必要的反马尔科夫尼科夫加成反应，如甲醇或水等亲核试剂。
Photoinduced electron transfer (PET) 1 has in our hands turned out to be a viable tool for the synthesis of mono-and polycyclic terpenoid skeletons2 which are assembled via regioselective oxidation of terpenoid polyalkenes at the omega alkene sites. Such oxidations, generating the parent radical cations, give rise to (a) trapping of the radical cations by a nucleophile, such as water,(b) radical-type cyclization (s), and (c) termination of such processes either by reduction/protonation at the resulting tertiary radical center of the cyclization products or by trapping of this center by a hydrogen atom (Scheme 1). 3 Depending on the electron-withdrawing properties of the substituent (s) R1/2 of the polyalkene chain, 6-endo (f 2) vs 5-exo-trig (f 3) ring closures terminate the cyclization of 1.Such PET-triggered cascade cyclizations were found to mimic the parent nonoxidative enzymatic processes4 which in turn have originally been proposed to proceed via cationic intermediates, generated upon enzymatic protonation and anti-Markovnikov addition of water. A representative example of such transformations is that of squalene to tetrahymanol. 4b However, the latter proposal has so far not been validated in vitro. The present principle, based on the intermediacy of radical cations, which are generated photochemically from readily accessible terpenoid polyalkenes, provides nature-like cascade cyclizations, including the requisite anti-Markovnikov addition of a nucleophile, such as methanol or water.