Felix Flachsmann, Natalie Aeberli, Sandro Dossenbach, Lucas Hortencio, Heinz Koch, Gerhard Brunner, Benjamin Spenger, Eric Eichhorn, Alessio Fonzo, Raphael Berweger, Dominique Lelièvre
{"title":"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","authors":"Felix Flachsmann, Natalie Aeberli, Sandro Dossenbach, Lucas Hortencio, Heinz Koch, Gerhard Brunner, Benjamin Spenger, Eric Eichhorn, Alessio Fonzo, Raphael Berweger, Dominique Lelièvre","doi":"10.1002/hlca.202400016","DOIUrl":null,"url":null,"abstract":"<p>All eight theoretical stereoisomers of (10<i>S</i>)-Ambrox have been synthesized by enzymatic polycyclization of the four geometric isomers of homofarnesol with selected squalene hopene cyclases. This includes the highly strained (+)-(8<i>S</i>,9<i>S)-</i>Ambrox, an isomer historically considered unlikely to exist. The enantiomeric (10<i>R</i>)-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-<i>epi</i>-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 (8<i>R</i>)-configuration was identified as the single most important structural feature for high odour strength.</p>","PeriodicalId":12842,"journal":{"name":"Helvetica Chimica Acta","volume":"107 7","pages":""},"PeriodicalIF":1.5000,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Ambrox through the Looking Glass: Chemoenzymatic Synthesis and GC-Olfactometric Analysis of 15 Ambrox Stereoisomers\",\"authors\":\"Felix Flachsmann, Natalie Aeberli, Sandro Dossenbach, Lucas Hortencio, Heinz Koch, Gerhard Brunner, Benjamin Spenger, Eric Eichhorn, Alessio Fonzo, Raphael Berweger, Dominique Lelièvre\",\"doi\":\"10.1002/hlca.202400016\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>All eight theoretical stereoisomers of (10<i>S</i>)-Ambrox have been synthesized by enzymatic polycyclization of the four geometric isomers of homofarnesol with selected squalene hopene cyclases. This includes the highly strained (+)-(8<i>S</i>,9<i>S)-</i>Ambrox, an isomer historically considered unlikely to exist. The enantiomeric (10<i>R</i>)-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-<i>epi</i>-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 (8<i>R</i>)-configuration was identified as the single most important structural feature for high odour strength.</p>\",\"PeriodicalId\":12842,\"journal\":{\"name\":\"Helvetica Chimica Acta\",\"volume\":\"107 7\",\"pages\":\"\"},\"PeriodicalIF\":1.5000,\"publicationDate\":\"2024-05-08\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Helvetica Chimica Acta\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/hlca.202400016\",\"RegionNum\":4,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"CHEMISTRY, MULTIDISCIPLINARY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Helvetica Chimica Acta","FirstCategoryId":"92","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/hlca.202400016","RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
Ambrox through the Looking Glass: Chemoenzymatic Synthesis and GC-Olfactometric Analysis of 15 Ambrox Stereoisomers
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.
期刊介绍:
Helvetica Chimica Acta, founded by the Swiss Chemical Society in 1917, is a monthly multidisciplinary journal dedicated to the dissemination of knowledge in all disciplines of chemistry (organic, inorganic, physical, technical, theoretical and analytical chemistry) as well as research at the interface with other sciences, where molecular aspects are key to the findings. Helvetica Chimica Acta is committed to the publication of original, high quality papers at the frontier of scientific research. All contributions will be peer reviewed with the highest possible standards and published within 3 months of receipt, with no restriction on the length of the papers and in full color.