ASSIGNMENT OF THE ABSOLUTE-CONFIGURATION OF NATURAL LENTIGINOSINE BY SYNTHESIS AND ENZYMATIC ASSAYS OF OPTICALLY PURE (-ENANTIOMERS AND (-)-ENANTIOMERS())

The structure and absolute configuration of natural lentiginosine isol ated from plant sources was determined to be (1S,2S,8aS)-1,2-dihydroxy indolizidine ((+)-4) on the basis of the synthesis of both enantiomers (+)-4 and (-)-4 and their inhibition of amyloglucosidases. Alkaloid ( +)-4 was derived from (L)-(+)-tartaric acid via a highly stereo- and r egioselective 1,3-dipolar cycloaddition of (3S,4S)-3 ,4-bis[(tert-buty ldiphenylsilyl)oxy]-1-pyrroline N-oxide to methylenecyclopropane, foll owed by thermal rearrangement of the adduct into rt-butyldiphenylsily) oxy]octahydroindolizin-7-one. The enantiomer (-)-4 was derived in the same way from (D)-(-)-tartaric acid. Both (+)-4 and (-)-4 displayed in hibition specificity for amyloglucosidases, being inactive toward 17 o ther glycosidases. With amyloglucosidase from Aspergillus niger, synth etic (+)-4 displayed inhibition (K-i = 2 mu M) 5 times stronger than t hat reported for natural lentiginosine, 35 times that measured for (-) -4, and twice that of castanospermine. Alkaloid (+)-4 is thus the most potent and specific competitive inhibitor of amyloglucosidases among azasugars and their analogues.