用脱氧芳构化策略立体选择性合成linusteastat

IF 4.7 1区化学 Q1 CHEMISTRY, ORGANIC

Organic Letters Pub Date : 2026-10-14 DOI:10.1021/acs.orglett.6c03795

Santhosh Reddy Naini,Tony Hudgens,Luis Sierra,Leena Hirvelä,Anji Chen,Chengfeng Ye,Huiping Zhao,Xueyi Zhang,Madhusudhan Reddy Gadi,Mohammed Sharique,Jiezhen Li,Rahul D. Shingare,Praveen Gajula,Nageswara Kalikinidi,Manasa Mamunooru,Jonathan Bietsch,Zhirui Wang,Rajender Reddy Leleti,Bo Qu,Chris H. Senanayake

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引用次数: 0

摘要

摘要：本文报道了一种高效的立体选择性合成Linustedastat(1)的方法，该方法从廉价的、市售的西妥内酯开始。该路线的特点是高化学选择性格氏加成，其次是顺序的双醛缩合，以构建核心甾体框架。关键的一步包括氟化类固醇中间体的新型脱氧芳构化，为立体选择性氢化和1,4共轭加成奠定了基础，以进一步精制分子。这一精心设计的序列在16步中提供了复杂的缺乏电子的氟化甾体结构，总收率为11.0%。

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Stereoselective Synthesis of Linustedastat Via Deoxy-Aromatization Strategy

Abstract An efficient and stereoselective synthesis of Linustedastat (1) is reported, commencing from inexpensive and commercially available sitolactone. The route features a highly chemoselective Grignard addition, followed by sequential double aldol condensations to construct the core steroidal framework. A key step involves a novel deoxy-aromatization of a fluorinated steroid intermediate, setting the stage for a stereoselective hydrogenation and a 1,4-conjugate addition to further elaborate the molecule. This strategically designed sequence delivers the complex and electron-deficient fluorinated steroidal architecture in 16 steps with an 11.0% overall yield.

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来源期刊

Organic Letters 化学-有机化学

CiteScore

9.30

自引率

11.50%

发文量

1607

审稿时长

1.5 months

期刊介绍： Organic Letters invites original reports of fundamental research in all branches of the theory and practice of organic, physical organic, organometallic,medicinal, and bioorganic chemistry. Organic Letters provides rapid disclosure of the key elements of significant studies that are of interest to a large portion of the organic community. In selecting manuscripts for publication, the Editors place emphasis on the originality, quality and wide interest of the work. Authors should provide enough background information to place the new disclosure in context and to justify the rapid publication format. Back-to-back Letters will be considered. Full details should be reserved for an Article, which should appear in due course.