A practical synthesis of three aliphatic metabolites of capsaicin: 16-Hydroxycapsaicin, 17-hydroxycapsaicin, and 16,17-dehydrocapsaicin

• Published in: Synthetic communications Vol. 53; no. 11; pp. 771 - 778
• Main Authors: Li, Die, Guo, Lulu, Guo, Xiaodong, Mao, Jian, Liu, Fuqiang, Chai, Guobi, Shi, Qingzhao, Ji, Lingbo, Wang, Dingzhong, Zhang, Qidong, Fan, Wu
• Format: Journal Article
• Language: English
• Published: PHILADELPHIA Taylor & Francis 03.06.2023; Taylor & Francis Ltd
• Subjects: Aliphatic compounds; Capsaicin metabolites; Chemistry; Chemistry, Organic; Hydroboration; hydroboration-oxidation; Hydroxyl groups; Ketones; Metabolites; Metathesis; olefin metathesis; Oxidation; Physical Sciences; Science & Technology; Synthesis; Wittig reaction; olefin metathesis; Wittig reaction; Capsaicin metabolites; hydroboration-oxidation
• ISSN: 0039-7911; 1532-2432
• DOI: 10.1080/00397911.2023.2195113

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 Ph 3 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.