Synthesis of (R) and (S)-aminocarnitine, (R) and (S)-4-phosphonium-3-amino-butanoate, (R) and (S) 3,4-diaminobutanoic acid, and their derivatives starting from D- and L-aspartic acid

Process for the preparation of compounds with the formula:

• 4
• in which
• W is Q(CH3)3 where Q is N or P or
• W is NH3
• Y is hydrogen or one of the following groups:
• —R1,
• —COR1,
• —CSR1,
• —COOR1,
• —CSOR1,
• —CONHR1,
• —CSNHR1,
• —SOR1,
• —SO2R1,
• —SONHR1,
• —SO2NHR1,
• where
• R1 is a straight or branched, saturated or unsaturated alkyl containing from 1 to 20 carbon atoms, optionally substituted with an A1 group, where A1 is selected from the group consisting of halogen, C6-C14 aryl or heteroaryl, aryloxy or heteroaryloxy, which can optionally be substituted with straight or branched, saturated or unsaturated lower alkyl or alkoxy, containing from 1 to 20 carbon atoms, halogens;
• said process comprises the following steps:
• a) conversion of D-aspartic or L-aspartic acid to N—Y substituted D-aspartic or L-aspartic acid;
• b) conversion of the N—Y substituted D-aspartic or L-aspartic acid to the respective anhydride;
• c) reduction of the anhydride obtained in step b) to the corresponding 3-(NH—Y)-lactone;
• d) opening of the lactone obtained in step c) to yield the corresponding D- or L-3-(NH—Y)-amino-4-hydroxybutyric acid;
• e) transformation of the 4-hydroxy group of the D- or L-3-(NH—Y)-amino-4-hydroxybutyric acid into a leaving group;
• f) substitution of the leaving group in position 4 of the D- or L-3-(NH—Y)-aminobutyric acid with a trimethylammonium group, or trimethylphosphonium group;
• g) hydrolysis of the ester group;
• and, if so desired,
• h) restoration of the amino group;
• i) one pot hydrolysis of the ester and protective group on N group at position 3;
• l) substitution of the leaving group in position 4 of the D- or L-3-(NH—Y)-aminobutanoic acid with an azido group;
• m) reduction of the azido group to amino group and concurrent hydrolysis of the ester group, and if so desired,
• n) restoration of the amino group.