Rajat Ghosh, Manisha Kundu, Prof. Dr. Shital K. Chattopadhyay
{"title":"一种天然环四肽的两种立体异构体和四种二异肽的后期支架分化合成","authors":"Rajat Ghosh, Manisha Kundu, Prof. Dr. Shital K. Chattopadhyay","doi":"10.1002/ajoc.202500232","DOIUrl":null,"url":null,"abstract":"<p>A concise synthetic route has been developed to access two stereoisomers 5a-b of a biologically enticing naturally occurring cyclic tetrapeptide through late-stage diversification of the cyclopeptidic scaffold 8. A cross-metathesis reaction of this template with the olefins 9a-b, preparaed from enantiomeric methyl lactates 10, produced the α,β-unsaturated ketones 7a-b which on subsequent hydrogenation produced the desired targets 5a-b in good overall yields.These two stereo-isomers, 5a-b, were then used for the preparation of four stereoisomers of the closely related and biologically relevant cyclic tetrapeptide diheteropeptin 1. A syn-selective reduction of the hydroxyketones 5a-b with lithium tri-tert-butoxyaluminium hydride produced the syn-isomers 1a and 1c, whereas an anti-selective reduction with lithium triethylborohydride produced the pseudo-enantiomeric targets 1b and 1d with similar yield and selectivity. Thus, an ensemble of six cyclic tetrapeptides with stereochemical diversity was generated from the common template 8 in two-three steps.</p>","PeriodicalId":130,"journal":{"name":"Asian Journal of Organic Chemistry","volume":"14 9","pages":""},"PeriodicalIF":2.7000,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Synthesis of Two Stereoisomers of a Natural Cyclotetrapeptide and Four Stereoisomeric Diheteropeptins Through Late-Stage Scaffold Diversification\",\"authors\":\"Rajat Ghosh, Manisha Kundu, Prof. Dr. Shital K. Chattopadhyay\",\"doi\":\"10.1002/ajoc.202500232\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>A concise synthetic route has been developed to access two stereoisomers 5a-b of a biologically enticing naturally occurring cyclic tetrapeptide through late-stage diversification of the cyclopeptidic scaffold 8. A cross-metathesis reaction of this template with the olefins 9a-b, preparaed from enantiomeric methyl lactates 10, produced the α,β-unsaturated ketones 7a-b which on subsequent hydrogenation produced the desired targets 5a-b in good overall yields.These two stereo-isomers, 5a-b, were then used for the preparation of four stereoisomers of the closely related and biologically relevant cyclic tetrapeptide diheteropeptin 1. A syn-selective reduction of the hydroxyketones 5a-b with lithium tri-tert-butoxyaluminium hydride produced the syn-isomers 1a and 1c, whereas an anti-selective reduction with lithium triethylborohydride produced the pseudo-enantiomeric targets 1b and 1d with similar yield and selectivity. Thus, an ensemble of six cyclic tetrapeptides with stereochemical diversity was generated from the common template 8 in two-three steps.</p>\",\"PeriodicalId\":130,\"journal\":{\"name\":\"Asian Journal of Organic Chemistry\",\"volume\":\"14 9\",\"pages\":\"\"},\"PeriodicalIF\":2.7000,\"publicationDate\":\"2025-07-11\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Asian Journal of Organic Chemistry\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://aces.onlinelibrary.wiley.com/doi/10.1002/ajoc.202500232\",\"RegionNum\":4,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, ORGANIC\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Asian Journal of Organic Chemistry","FirstCategoryId":"92","ListUrlMain":"https://aces.onlinelibrary.wiley.com/doi/10.1002/ajoc.202500232","RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, ORGANIC","Score":null,"Total":0}
Synthesis of Two Stereoisomers of a Natural Cyclotetrapeptide and Four Stereoisomeric Diheteropeptins Through Late-Stage Scaffold Diversification
A concise synthetic route has been developed to access two stereoisomers 5a-b of a biologically enticing naturally occurring cyclic tetrapeptide through late-stage diversification of the cyclopeptidic scaffold 8. A cross-metathesis reaction of this template with the olefins 9a-b, preparaed from enantiomeric methyl lactates 10, produced the α,β-unsaturated ketones 7a-b which on subsequent hydrogenation produced the desired targets 5a-b in good overall yields.These two stereo-isomers, 5a-b, were then used for the preparation of four stereoisomers of the closely related and biologically relevant cyclic tetrapeptide diheteropeptin 1. A syn-selective reduction of the hydroxyketones 5a-b with lithium tri-tert-butoxyaluminium hydride produced the syn-isomers 1a and 1c, whereas an anti-selective reduction with lithium triethylborohydride produced the pseudo-enantiomeric targets 1b and 1d with similar yield and selectivity. Thus, an ensemble of six cyclic tetrapeptides with stereochemical diversity was generated from the common template 8 in two-three steps.
期刊介绍:
Organic chemistry is the fundamental science that stands at the heart of chemistry, biology, and materials science. Research in these areas is vigorous and truly international, with three major regions making almost equal contributions: America, Europe and Asia. Asia now has its own top international organic chemistry journal—the Asian Journal of Organic Chemistry (AsianJOC)
The AsianJOC is designed to be a top-ranked international research journal and publishes primary research as well as critical secondary information from authors across the world. The journal covers organic chemistry in its entirety. Authors and readers come from academia, the chemical industry, and government laboratories.