A practical synthesis of three aliphatic metabolites of capsaicin: 16-Hydroxycapsaicin, 17-hydroxycapsaicin, and 16, 17-dehydrocapsaicin. Issue 11 (3rd June 2023)

• Record Type: Journal Article
• Authors: Li, Die; Guo, Lulu; Guo, Xiaodong; Mao, Jian; Liu, Fuqiang; Chai, Guobi; Shi, Qingzhao; Ji, Lingbo; Wang, Dingzhong; Zhang, Qidong; Fan, Wu
• Is Part Of: Synthetic communications. Volume 53:Issue 11(2023)
• Page Start: 771
• Page End: 778
• Publication Date: 2023-06-03
• Subjects: Capsaicin metabolites -- hydroboration-oxidation -- olefin metathesis -- Wittig reaction; Organic compounds -- Synthesis -- Periodicals; Chemistry, Organic; Synthesis; 547.205
• DOI: 10.1080/00397911.2023.2195113
• Languages: English
• ISSNs: 0039-7911

Abstract

Abstract: The first straightforward synthesis of 16-hydroxycapsaicin, 17-hydroxycapsaicin and 16, 17-dehydrocapsaicin, the major aliphatic metabolites of capsaicin, is reported. The amidation of hept-6-enoic acid with vanillylamine hydrochloride, followed by olefin metathesis using 2-methylbut-3-en-2-ol as partner furnished 16-hydroxycapsaicin in 56.1% overall yield with excellent E -selectivity. The E -selective olefin metathesis of methyl hept-6-enoate with but-3-en-2-one led to α, β-unsaturated ketone compound, which was subject to Wittig reaction with Ph3 P + MeBr -, providing the corresponding 1, 3-diene derivative. After removing methyl group by hydrolysis and introducing hydroxyl group by hydroboration-oxidation, such diene could be further converted to 16, 17-dehydrocapsaicin and 17-hydroxycapsaicin with overall yields of 35.6 and 7.8%, respectively. GRAPHICAL ABSTRACT: UF0001