Stereoselective Synthesis of Benzannulated Spiroketals: Influence of the Aromatic Ring on Reactivity and Conformation

被引：37

作者：

Liu, Guodong ^{[1
]}

Wurst, Jacqueline M. ^{[2
]}

Tan, Derek S. ^{[1
,2
]}

机构：

[1] Mem Sloan Kettering Canc Ctr, Mol Pharmacol & Chem Program, New York, NY 10065 USA

[2] Mem Sloan Kettering Canc Ctr, Triinst Training Program Chem Biol, New York, NY 10065 USA

来源：

ORGANIC LETTERS | 2009年 / 11卷 / 16期

关键词：

DIVERSITY-ORIENTED SYNTHESIS; STEREOCONTROLLED SYNTHESIS; KINETIC SPIROCYCLIZATION; PAPULACANDIN-B; BERKELIC ACID; ANTIBIOTICS; CYCLIZATION; HYDROALKOXYLATION; SPIROACETALS; ETHERS;

D O I：

10.1021/ol901437f

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

A systematic stereocontrolled synthesis of benzannulated spiroketals has been developed, using kinetic spirocyclization reactions of glycal epoxides, leading to a new AcOH-induced cyclization and valuable insights into the reactivity and conformations of these systems. One stereochemical series accommodates axial positioning of the aromatic ring while another adopts an alternative C-1(4) chair conformation to avoid it. Equatorial aromatic rings also participate in nonobvious steric interactions that impact thermodynamic stability. A discovery library of 68 benzannulated spiroketals with systematic variations in stereochemistry, ring size, and positioning of the aromatic substituent has been synthesized for broad biological evaluation.

引用

页码：3670 / 3673

页数：4

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