Synthetic and Biosynthetic Studies on FR900482 and Mitomycin C:  An Efficient and Stereoselective Hydroxymethylation of an Advanced Benzazocane Intermediate

• Published in: Organic letters Vol. 9; no. 26; pp. 5341 - 5344
• Main Authors: Namiki, Hidenori, Chamberland, Stephen, Gubler, Daniel A, Williams, Robert M
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 20.12.2007; Amer Chemical Soc
• Subjects: Antineoplastic Agents - chemical synthesis; Azo Compounds - chemistry; Chemistry; Chemistry, Organic; Methylation; Mitomycin - chemical synthesis; Oxazines - chemical synthesis; Physical Sciences; Science & Technology; Stereoisomerism; ACTIVATION; AGENTS; INDUCTION; FORMALDEHYDE; ANTITUMOR DRUGS; (+)-FR900482
• ISSN: 1523-7060; 1523-7052
• DOI: 10.1021/ol701960v

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 β-hydroxy ketone may enable access to mitomycin C or FR900482 biosynthetic congeners.