Heterodendrin (l), the glucoside of (S)-2-hydroxy-3-methylbutanenitrile, belongs to a rapidly expanding family of natural products, also including proacacipetalin (2) and congeners (3,4), 3-hydroxyheterodendrin (5), cardiospermin and its esters (6,7), as well as cyanogenic lipids (8) and their allylically rearranged descendants (9). The boranical distribution of heterodendrin appears to be relatively broad, the glucoside being reported from the Sapindaceae (l), Rosaceae (6), Poaceae (lo), and a single species of the genus Acacia (Leguminosae) (11). Following our earlier study of proacacipetalin (2,12), we report now the isolation of heterodendrin from leaves of Acacia hebeclada DC. and Acacia giraffae Willd. Synthesis of heterodendrin was attempted by the Koenigs-Knorr condensation of α-acetobromoglucose with 2-hydroxy-3-methylbutanenitrile. In spite of numerous variations of the reaction conditions, the yield of the tetraacetates of heterodendrin and its epimer epiheterodendrin (13) was low. Thus, the evidence accumulates that the cyanohydrin approach (14-17) to synthesis of natural cyanohydrin glycosides, albeit more straightforward, is generally less efficient compared to the classical synthetic approach of Emil Fischer (18-20). Heterodendrin tetraacetate was also obtained by catalytic hydrogenation of proacacipetalin tetraacetate. The difference between the molecular rotations of heterodendrin tetraacetate and epiheterodendrin tetraacetate was =243'. The present report indicates that the co-occurrence of heterodendrin and proacacipetalin in Acacia may be quite general. Feeding experiments suggest that proacacipetalin is biosynthesized from L-leucine (21), although the hypothesis that proacacipetalin is formed by way of heterodendrin and its 3-hydroxylated derivative (5) has yet to be verified.