Synthetic and biosynthetic studies on FR900482 and mitomycin C: an efficient and stereoselective hydroxymethylation of an advanced benzazocane intermediate.
We report a simple, efficient, and stereoselective Mukaiyama aldol approach to install the key hydroxymethyl moiety into the benzazocane framework of FR900482. Synthetic investigations revealed that the reaction is highly dependent upon the electronics of the aromatic ring. This approach enabled the economical introduction of a [13C] label to study the biosynthesis of these structurally and biogenetically related natural products. Epimerization of the initially formed beta-hydroxy ketone may enable access to mitomycin C or FR900482 biosynthetic congeners.
Namiki
Hidenori
H
Department of Chemistry, Colorado State University, Fort Collins, Colorado 80523-1872, USA.
Chamberland
Stephen
S
Gubler
Daniel A
DA
Williams
Robert M
RM
D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D001391:Azo Compounds / Q000737:chemistry*; D008745:Methylation; D016685:Mitomycin / Q000138:chemical synthesis*; D010078:Oxazines / Q000138:chemical synthesis; D013237:Stereoisomerism
D000970:Antineoplastic Agents; D001391:Azo Compounds; D010078:Oxazines; C053335:FR 900482; D016685:Mitomycin