Toward a synthesis of hirsutellone B by the concept of double cyclization.
Toward a synthesis of hirsutellone B by the concept of double cyclization.
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DOI：
10.1021/jo401799f
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发表时间：
2013-10-04
期刊：
影响因子：
--
通讯作者：
Sorensen EJ
中科院分区：
文献类型：
--
作者：
Reber KP;Tilley SD;Carson CA;Sorensen EJ
这个帐户描述了一种策略，直接形成六个环中的三个发现在聚酮天然产物hirsutellone B通过一个新的环级联。我们的方法的关键步骤包括两个转化：一个大环形成，一个瞬态酰基烯酮的亲核捕获和一个分子内diols - alder反应，这两个反应都是通过适当功能化的多不饱和二恶英酮的热裂解而发生的。这些热诱导的“双环化”级联产生了三个新的键，四个连续的立体中心，以及相当一部分的毛甾酮b的多环结构。通过该工艺合成的高级内酯和内酯中间体具有毛甾酮框架的关键特征，包括立体化学致密的十氢芴核和应变的对环烷环。然而，试图通过跨环碳-碳键形成来完成hirsutellone B的碳骨架被竞争性的o -烷基化反应破坏了。这篇文章还记录了我们是如何通过对几种不同的合成策略的评估来适应这一不希望的结果的，以及我们最终实现了对毛甾酮B的正式全合成。
This account describes a strategy for directly forming three of the six rings found in the polyketide natural product hirsutellone B via a novel cyclization cascade. The key step in our approach comprises two transformations: a large-ring forming, nucleophilic capture of a transient acyl ketene and an intramolecular Diels–Alder reaction, both of which occur in tandem through thermolyses of appropriately functionalized, polyunsaturated dioxinones. These thermally induced “double cyclization” cascades generate three new bonds, four contiguous stereocenters, and a significant fraction of the polycyclic architecture of hirsutellone B. The advanced macrolactam and macrolactone intermediates that were synthesized by this process possess key features of the hirsutellone framework, including the stereochemically dense decahydrofluorene core and the strained para-cyclophane ring. However, attempts to complete the carbon skeleton of hirsutellone B via transannular carbon-carbon bond formation were undermined by competitive O-alkylation reactions. This account also documents how we adapted to this undesired outcome through an evaluation of several distinct strategies for synthesis, as well as our eventual achievement of a formal total synthesis of hirsutellone B.
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影响因子：
1.8
作者：
He, HY;Yang, HY;Carter, GT
通讯作者：
Carter, GT
DOI：
10.1002/anie.197508011
发表时间：
1975-01-01
期刊：
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION IN ENGLISH
影响因子：
--
作者：
APPEL, R
通讯作者：
APPEL, R
影响因子：
1.8
作者：
Huang, Mingzheng;Huang, Chong;Liu, Bo
通讯作者：
Liu, Bo
影响因子：
7.3
作者：
GUTHIKONDA, RN;CAMA, LD;CHRISTENSEN, BG
通讯作者：
CHRISTENSEN, BG
影响因子：
1.8
作者：
Halvorsen, Geoff T.;Roush, William R.
通讯作者：
Roush, William R.