Enantiospecific synthesis of 3-aza-6,8-dioxa-bicyclo[3.2.1]octane carboxylic acids from erythrose

✍ Scribed by Andrea Trabocchi; Gloria Menchi; Massimo Rolla; Fabrizio Machetti; Ilaria Bucelli; Antonio Guarna

• Publisher: Elsevier Science
• Year: 2003
• Tongue: French
• Weight: 196 KB
• Volume: 59
• Category: Article
• ISSN: 0040-4020
• DOI: 10.1016/s0040-4020(03)00773-7

✦ Synopsis

New methodology for the synthesis of enantiopure 3-aza-6,8-dioxa-bicyclo[3.2.1]octane-carboxylic acids belonging to 7-endo-BTAa sub-class of g/d amino acids is described. The novelty is the use of 2,3-O-isopropylidene-erythrose instead of meso-tartaric acid derivative, thus allowing us to perform an enantiospecific synthesis. Reductive amination of erythrolactol with aminoacetaldehyde diethylacetal or benzylamine, and subsequent acid cyclisation gave directly the amino alcohol scaffold. Protection of nitrogen as urethane and final alcohol oxidation afforded the Fmoc-, Boc-, and Cbz-amino acids. The new synthetic route was applied to multigram scale, thus resulting in a marked improvement of the synthesis of enantiopure 7-endo-BTG and 7-endo-BTK amino acids.