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 gamma/delta 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.
Enantiospecific Synthesis of 3-Aza-6,8-Dioxa-Bicyclo[3.2.1]Octane Carboxylic Acids from Erythrose.
Machetti Fabrizio;
2003
Abstract
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 gamma/delta 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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
