Total synthesis of cryptophycin analogues via a scaffold approach.
[reaction: see text] Allylation of in situ generated beta,gamma-unsaturated aldehydes affords rapid access to vinyl halide analogues of fragment A of the cryptophycins. Three scaffolds are prepared in gram quantities by a ring-closing metathesis approach. Derivatization via a variety of cross-coupling protocols is possible, which affords novel analogues of these potent antimitotic agents.
McCubbin
J Adam
JA
Davenport Laboratories, Department of Chemistry, University of Toronto, Ontario, Canada.
Maddess
Matthew L
ML
Lautens
Mark
M
D000447:Aldehydes / Q000737:chemistry; D050256:Antimitotic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018360:Crystallography, X-Ray; D047630:Depsipeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004951:Esterification; D008968:Molecular Conformation; D015394:Molecular Structure; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism; D014753:Vinyl Compounds / Q000737:chemistry
D000447:Aldehydes; D050256:Antimitotic Agents; D047630:Depsipeptides; D010456:Peptides, Cyclic; D014753:Vinyl Compounds; C088419:cryptophycin