Ambrox through the Looking Glass: Chemoenzymatic Synthesis and GC-Olfactometric Analysis of 15 Ambrox Stereoisomers

IF 16.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Accounts of Chemical Research Pub Date : 2024-05-08 DOI:10.1002/hlca.202400016

Felix Flachsmann, Natalie Aeberli, Sandro Dossenbach, Lucas Hortencio, Heinz Koch, Gerhard Brunner, Benjamin Spenger, Eric Eichhorn, Alessio Fonzo, Raphael Berweger, Dominique Lelièvre

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引用次数: 0

Abstract

All eight theoretical stereoisomers of (10S)-Ambrox have been synthesized by enzymatic polycyclization of the four geometric isomers of homofarnesol with selected squalene hopene cyclases. This includes the highly strained (+)-(8S,9S)-Ambrox, an isomer historically considered unlikely to exist. The enantiomeric (10R)-series has been prepared by a combination of diastereoselective synthesis and preparative chiral HPLC. Thus, for the first time, the synthesis and sensory properties of all but one stereoisomers of Ambrox are presented. The results solve a long standing peradventure: the commercial product (−)-Ambrox exhibits by far the strongest odour, the previously described 9-epi-Ambrox is 26 times weaker. The enantiomer difference between (−)-and (+)-Ambrox was also found much higher than in previous reports (1000 vs. 8 times). The (8R)-configuration was identified as the single most important structural feature for high odour strength.

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透过玻璃看氨溴索15 种氨溴索立体异构体的化学酶法合成和气相色谱-反应监测分析

10S-Ambrox 的所有八种理论立体异构体都是通过酶法多环化同法尔酮醇的四种几何异构体与选定的角鲨烯烯环酶合成的。其中包括高度紧张的(+)-(8S,9S)-Ambrox，这是一种历来被认为不太可能存在的异构体。对映体 10R 系列是通过非对映选择性合成和制备性手性高效液相色谱相结合的方法制备的。因此，除了一种立体异构体之外，我们首次展示了所有氨溴索立体异构体的合成和感官特性。研究结果解决了一个长期存在的难题：(-)-Ambrox 是迄今为止气味最重的商品，而之前描述的 9-epi-Ambrox 的气味要弱 26 倍。研究还发现，(-)-Ambrox 和 (+)-Ambrox 之间的对映体差异也比以前的报告要大得多（1000 倍对 8 倍）。(8R)-构型被认为是高气味强度最重要的结构特征。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Accounts of Chemical Research 化学-化学综合

CiteScore

31.40

自引率

1.10%

发文量

312

审稿时长

2 months

期刊介绍： Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.