中科院上海有机化学研究所桂敬汉团队报道了仿生SN2′环化作用下重排类固醇Phomarol的不对称全合成。相关研究成果于2023年4月12日发表于国际一流学术期刊《美国化学会杂志》。

Phomarol是一种结构不寻常的1（10→ 19） 具有伪对称环庚烯-1，3-二醇基序、芳香族B环和高度官能化的四氢吡喃环的阿贝奥类固醇。

该文中，研究人员报道了通过收敛片段偶联方法从廉价的谷内酯13步合成这种天然产物。关键的转化包括非对映选择性烯丙基硼化、脱羧消除、Schnecker–Baran C–H羟基化、仿生SN2′环化和后期6π电环化。机理研究表明，四氢吡喃环的关键形成是通过甲硅烷基迁移/分子内SN2′环化级联反应发生的，而不是通过环氧化物开放过程。

附：英文原文

Title: Asymmetric Total Synthesis of the Rearranged Steroid Phomarol Enabled by a Biomimetic SN2′ Cyclization

Author: Xudong Wang, Ganlin Huang, Yun Wang, Jinghan Gui

Issue&Volume: April 12, 2023

Abstract: Phomarol is a structurally unusual 1(10 → 19)abeo-steroid with a pseudo-symmetrical cycloheptene-1,3-diol motif, an aromatic B ring, and a densely functionalized tetrahydropyran ring. Herein, we report a 13-step synthesis of this natural product from inexpensive sitolactone by means of a convergent fragment-coupling approach. Key transformations include a diastereoselective allylboration, a decarboxylative elimination, a Schnecker–Baran C–H hydroxylation, a biomimetic SN2′ cyclization, and a late-stage 6π electrocyclization. Mechanistic studies indicate that the pivotal formation of the tetrahydropyran ring occurs via a silyl migration/intramolecular SN2′ cyclization cascade rather than via an epoxide-opening process.

DOI: 10.1021/jacs.3c02817

Source: https://pubs.acs.org/doi/10.1021/jacs.3c02817