STEREOSELECTIVE SYNTHESIS OF ALL 4 ISOMERS OF CORONAMIC ACID - A GENERAL-APPROACH TO 3-METHANOAMINO ACIDS

A general approach to the synthesis of enantiomerically enriched 3-met hanoamino acids is presented where the cyclopropyl unit was introduced by a stereoselective cyclopropanation using a D-glucose-derived chira l auxiliary. This methodology was applied to the synthesis of the four stereoisomers of coronamic acid 14, 17, 20, and 22. Starting with the readily available allylic alcohol 5, beta-D-glucopyranoses (E)-6 and (E)-7 have been selectively prepared using trichloroacetimidate 2. The se olefins were cyclopropanated with very high diastereoselectivities using Et(2)Zn/CH2I2 (greater than or equal to 98% de) and Et(2)Zn/CH2I CI (greater than or equal to 97% de) in yields greater than 90%. After cleavage of the chiral auxiliary by ring contraction of the 2 O-trifl yl derivative of cyclopropanes 8 and 9, cyclopropylmethanols (-)-10 an d (+)-11 have been transformed to all four isomeric protected amino ac ids by selective protecting group manipulations, oxidation of primary alcohols, and Curtius rearrangement.