Total Synthesis of (−)‐Morphine |
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Authors: | Dr Hifumi Koizumi Dr Satoshi Yokoshima Prof?Dr Tohru Fukuyama |
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Institution: | Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7‐3‐1 Hongo, Bunkyo‐ku, Tokyo 113‐0033 (Japan), Fax: (+81)?3‐5802‐8694 |
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Abstract: | We have developed an efficient total synthesis of (?)‐morphine in 5 % overall yield with the longest linear sequence consisting of 17 steps from 2‐cyclohexen‐1‐one. The cyclohexenol unit was prepared by means of an enzymatic resolution and a Suzuki–Miyaura coupling as key steps. Construction of the morphinan core features an intramolecular aldol reaction and an intramolecular 1,6‐addition. Furthermore, mild deprotection conditions to remove the 2,4‐dinitrobenzenesulfonyl (DNs) group enabled the facile construction of the morphinan skeleton. We have also established an efficient synthetic route to a cyclohexenol unit containing an N‐methyl‐DNs‐amide moiety. |
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Keywords: | alkaloids cross‐coupling enzyme catalysis Michael addition total synthesis |
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