A biosynthetic proposal for ring formation in the antitumor agent halichomycin. Asymmetric synthesis of the AB-carbon backbone of halichomycin.
[reaction: see text] A biosynthetic proposal for ring formation in the antitumor agent halichomycin is presented in which macrocyclization of the putative prehalichomycin intermediate 1 is the first step. Compound 2 then undergoes dehydration to the alpha-keto N-acylimine 3 followed by tandem nucleophilic addition of the C(16)-hydroxyl to form the hemimacrolactam. A stereospecific Michael ring closure and enol protonation complete C-ring assembly. So far, synthetic efforts toward 1 have resulted in 8.
Hale
Karl J
KJ
The Christopher Ingold Laboratories, University College London, 20 Gordon Street, London WC1H 0AJ, England. k.j.hale@ucl.ac.uk
Dimopoulos
Paschalis
P
Cheung
Maxine L F
ML
Frigerio
Mark
M
Steed
Jonathan W
JW
Levett
Philip C
PC
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry*; D002244:Carbon / Q000737:chemistry*; D006576:Heterocyclic Compounds, 4 or More Rings / Q000737:chemistry* / Q000378:metabolism
D000970:Antineoplastic Agents; D006576:Heterocyclic Compounds, 4 or More Rings; C454439:halichomycin; D002244:Carbon