Total synthesis of (-)-colchicine via a Rh-triggered cycloaddition cascade.
[reaction: see text] A synthesis of the antimitotic alkaloids (-)-colchicine and (-)-isocolchicine is reported. Important steps are (a) enantioselective transfer-hydrogenation of an alkynone, (b) iodine/magnesium exchange with subsequent aromatic acylation, (c) Rh-catalyzed transformation of an alpha-diazoketone into an oxatetracyclic key intermediate through intramolecular [3 + 2]-cycloaddition of an in situ generated carbonyl ylide, and (d) regioselective conversion of the cycloadduct into a tropolone derivative. The new synthetic strategy opens an efficient enantioselective access to colchicine and structural analogues.
Graening
Timm
T
Universität zu Köln, Greinstrasse 4, D-50939 Köln, Germany.
Bette
Virginie
V
Neudörfl
Jörg
J
Lex
Johann
J
Schmalz
Hans-Günther
HG
D003078:Colchicine / Q000138:chemical synthesis* / Q000737:chemistry; D018360:Crystallography, X-Ray; D003500:Cyclization; D008958:Models, Molecular; D015394:Molecular Structure; D012238:Rhodium / Q000737:chemistry*
D012238:Rhodium; D003078:Colchicine