Novel metal complex synthons for chiral 4-azaleucine, 2,3-diaminopropanoic acid and its elaboration

Efficient syntheses of chiral Co(III) complexes with 2,3-diaminopropanoic acid (A,pr) have been developed. In these complexes, the amino acid zwitterion [A(2)pr(H+)O-] is bound didentate through the carboxylate and N-2-amine groups while the N-3-ammonio group [pK(a) = 7.19(2)] is unprotected. Syntheses of Lambda(+)(578)- and Delta(-)(578)-[(en)(2)Co(S-A(2)pr(H+)O)]Cl-3. H2O were effected stereoretentively from the similarly didentate aspartato complexes Lambda- and Delta-[(en)(2)Co(S-Asp(OH)O)]Cl-2 in reaction sequences transforming the unbound beta-carboxyl group into an amine by Curtius rearrangement. The absolute configuration of the Lambda(+)(578)-[(en)(2)Co(S-Asp(OH)O)](ClO4)(2) complex was determined by X-ray crystallographic analysis and defined the absolute stereochemistry of diastereoisomers and derived products. Methylation of the N-3-amine group of Lambda(+)(578)-[(en)(2)Co(S-A(2)pr(H+)O)]Cl-3. H2O gave the (S)-4-azaleucine complex Lambda(+)(578)-[(en)(2)Co(S-A(2)pr(Me2H+)O)](C4F9SO3)(3) from which enantiopure (+)-(S)-2-amino-3-(dimethylamino)propanoic acid dihydrochloride hemihydrate [=(+)-(S)-A(2)pr(Me-2). 2HCl . 0.5H(2)O] was obtained upon reductive removal of the protecting Co(III) centre. Racemic 4-azaleucine was easily produced by an alternative but also metal-dependent method and the intermediate rac-(p)-[(tren)Co(A(2)pr(Me2H+)O)]Zn2Cl7. 3H(2)O obtained in a simple solid-phase synthesis by selective reduction of achiral (p)-[(tren)Co(2-amino-3-(dimethylamino)a chloride)](3+) ion adsorbed on AG 50W-X2 cation exchange resin. The epimerization rate of the Lambda-[(en)(2)Co(S-A(2)prO)](2+) complex ion was first-order in [HO-] [k(E) = 3.8 x 10(-2) dm(3) mol(-1) s(-1), I = 1.00 M (NaClO4), 25 degrees C] with the diastereoisomer ratio K-C(=[Lambda-R]/[Lambda-S]) = 0.77(2) at equilibrium in 10 mM NaOH. However, no epimerization was observed after at least 3 hours in 6 M HCl at 45 degrees C.