Total synthesis of (-)-morphine.
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.
Koizumi
Hifumi
H
Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Yokoshima
Satoshi
S
Fukuyama
Tohru
T
D055162:Biocatalysis; D004798:Enzymes / Q000737:chemistry / Q000378:metabolism; D009020:Morphine / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
D004798:Enzymes; D009020:Morphine