Meroterpenoid Synthesis via Sequential Polyketide Aromatization and Radical Anion Cascade Triene Cyclization: Biomimetic Total Syntheses of Austalide Natural Products

被引:16
作者
Ma, Tsz-Kan [1 ]
Parsons, Philip J. [1 ]
Barrett, Anthony G. M. [1 ]
机构
[1] Imperial Coll, Dept Chem, Mol Sci Res Hub, White City Campus,Wood Lane, London W12 0BZ, England
基金
英国工程与自然科学研究理事会;
关键词
PENICILLIUM-THOMII MAIRE; ASPERGILLUS-USTUS; METABOLITES; BIOSYNTHESIS;
D O I
10.1021/acs.joc.9b00142
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
The first total synthesis of five austalide natural products, (+)-17S-dihydroaustalide K, (+/-)-austalide K, (+/-)-13-deacetoxyaustalide I, (+/-)-austalide P, and (+/-)-13-deoxyaustalide Q acid, was accomplished via a series of biomimetic transformations. Key steps involved polyketide aromatization of a trans,trans-farnesol-derived beta,delta-diketodioxinone into the corresponding beta-resorcylate, followed by titanium(III)-mediated reductive radical cyclization of an epoxide to furnish the drimene core. Subsequent phenylselenonium ion induced diastereoselective cyclization of the drimene completed the essential carbon framework of the austalides to access (+/-)-17S-dihydroaustalide K, (+/-)-austalide K, and (+/-)-13-deacetoxyaustalide I via sequential oxidations. Furthermore, (+/-)-13-deacetoxyaustalide I could serve as a common intermediate to be derivatized into other related natural products, (+/-)-austalide P and (+/-)-13-deoxyaustalide Q acid, by functionalizing the cyclic lactone moiety.
引用
收藏
页码:4961 / 4970
页数:10
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