Total synthesis of (-)- and ent-(+)-vindoline and related alkaloids.
A concise 11-step total synthesis of (-)- and ent-(+)-vindoline (3) is detailed based on a unique tandem intramolecular [4 + 2]/[3 + 2] cycloaddition cascade of a 1,3,4-oxadiazole inspired by the natural product structure, in which three rings and four C-C bonds are formed central to the characteristic pentacyclic ring system setting all six stereocenters and introducing essentially all the functionality found in the natural product in a single step. As key elements of the scope and stereochemical features of the reaction were defined, a series of related natural products of increasing complexity were prepared by total synthesis including both enantiomers of minovine (4), 4-desacetoxy-6,7-dihydrovindorosine (5), 4-desacetoxyvindorosine (6), and vindorosine (7) as well as N-methylaspidospermidine (11). Subsequent extensions of the approach provided both enantiomers of 6,7-dihydrovindoline (8), 4-desacetoxyvindoline (9), and 4-desacetoxy-6,7-dihydrovindoline (10).
Ishikawa
Hayato
H
Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
Elliott
Gregory I
GI
Velcicky
Juraj
J
Choi
Younggi
Y
Boger
Dale L
DL
D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry; D003500:Cyclization; D015394:Molecular Structure; D013237:Stereoisomerism; D014747:Vinblastine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry
D000470:Alkaloids; D000970:Antineoplastic Agents; C008532:minovine; C009667:vindoline; D014747:Vinblastine; C514721:vindorosine