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Total Synthesis of (−)‐Morphine
Author(s) -
Koizumi Hifumi,
Yokoshima Satoshi,
Fukuyama Tohru
Publication year - 2010
Publication title -
chemistry – an asian journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.18
H-Index - 106
eISSN - 1861-471X
pISSN - 1861-4728
DOI - 10.1002/asia.201000458
Subject(s) - intramolecular force , moiety , aldol reaction , amide , yield (engineering) , total synthesis , chemistry , stereochemistry , nitrogen atom , sequence (biology) , combinatorial chemistry , group (periodic table) , organic chemistry , catalysis , materials science , metallurgy , biochemistry
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.