STEREOSELECTIVE SYNTHESIS OF 2,3-DIAMINO ACIDS - 2,3-DIAMINO-4-PHENYLBUTANOIC ACID

The synthesis of (2S,3S)- and (2S,3fl)-2,3-diamino-4-phenylbutanoic acid (lc and 3) from L-aspartic acid is described. The N-(phenylfluorenyl)-protected aspartic acid diesters 4 and 10 (a-tert-butyl, β-methyl), 18 03-benzyl, α-tert-butyl), and 28 (β-benzyl,α-methyl) are regioselectively benzylated at C-3 by using KHMDS and benzyl bromide or iodide. Whereas the alkylation of compounds 4 and 28 proceeds in low to moderate diastereoselectivities, derivatives 10 and 18 gave the corresponding diastereomers in ratios of up to 30/1. Selective cleavage of the β ester followed by Curt 3 degradation using diphenyl phosphorazidate (DPPA) gives rise to 2,3-diamino derivatives that are subsequently transformed into lc or 3. Depending on the nature of the ester groups and the N-protection, substrates 4, 18, and 28 can serve for different purposes. Whereas 4 leads to a mixture of both diastereomers, which are easily separated as the cyclic ureas 7a and 7b, use of diester 18 allows the direct preparation of the 2S,3S isomer in high selectivity. Finally, compound 28 permits the preparation of esters of 2,3-diamino acids with differentially protected amino groups. Since we have demonstrated previously that the C-3 alkylation of N- (phenylfluorenyl)aspartates is a general reaction, this method provides general access to 2,3-diamino acids. © 1990, American Chemical Society. All rights reserved.