Synthesis of a water-soluble chiral NMR shift reagent: (S)-PDTA

A five-step synthesis of the water-soluble chiral polydentate ligand, (S)-PDTA [(S)-PDTA = N,N,N′,N′-tetrakis[(hydroxycarbonyl)methyl]-(S)-1,2-diaminopropane] starting from l-alanine has been worked out, via steps with retention of chirality. Total yield is 50.7% (average of ∼88% for each step), while published methods report 33.4% total yield over four steps.

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l-(S)-Alanine methyl ester hydrochlorideC4H10ClNO2[α]D20=+4.1 (c 9.83, CH3OH)Absolute configuration: (S)

l-(S)-AlanylamideC3H10Cl2N2O[α]D20=+10.0 (c 9.33, CH3OH)Absolute configuration: (S)

(S)-N,N,N′,N′-Tetrakis[(ethoxy-carbonyl)methyl]-1,2-diaminopropaneC15H34N2O8[α]D20=+1.4 (c 8.53, CHCl3)Absolute configuration: (S)

(S)-N,N,N′,N′-Tetrakis[(hydroxy-carbonyl)methyl]-1,2-diamino-propane dihydrochlorideC11H20Cl2N2O8[α]D20=+24.7 (c 25.20, CH3OH)Absolute configuration: (S)