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

摘要

Efficient syntheses of chiral Co(III) complexes with 2, 3-diaminopropanoic acid (A_2pr) have been developed. In these complexes, the amino acid zwitterion [A_2pr(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)_2Co(S-A_2pr(H~+)O)]Cl_3 centre dot H_2O were effected stereoretentively from the similarly didentate aspartato complexes #LAMBDA#- and #DELTA#-[(en)_2Co(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)_2Co(S-Asp(OH)O)](ClO_4)_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)_2Co(S-A_2pr(H~+)O)]Cl_3 centre dot H_2O gave the (S)-4-azaleucine complex #LAMBDA#(+)_(578)-[(en)_2Co(S-A_2pr(Me_2H~+)O)](C_4F_9SO_3)_3 from which enantiopure (+)-(S)-2-amino-3-(dimethylamino)propanoic acid dihydrochloride hemihydrate [=(+)-(S)-A_2pr(Me_2) centre dot 2HCl centre dot 0.5H_2O] was obtained upon reductive removal of the protecting Co(III) centre. Reacemic 4-azaleucine was easily produced by an alternative, but also metal-dependent method and the intermediate rac-(p)-[(tern)Co(A_2pr(Me_2H~+)O)]Zn_2Cl_7 centre dot 3H_2O obtained in a simple solid-phase synthesis by selective reduction of achiral (p)-[(tern)Co(2-amino-3-(dimethylamino)acrylyl chloride)]~(3+) ion adsorbed on AG 50W-X2 cation exchange resin. The epimerization rate of the #LAMBDA#-[(en)_2Co(S-A_2prO)]~(2+) complex ion was first-order in [HO~-] [#appa#_E = 3.8 * 10~(-2) dm~3 mol~(-1) s~(-1), I=1.00 m (NaClO_4), 25 deg 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 6M HCl at 45 deg C.