Synthesis of Enantiomerically Pure N-Boc-Protected 1,2,3-Triaminopropylphosphonates and 1,2-Diamino-3-Hydroxypropylphosphonates.

All possible isomers of 1,2,3-tri(--butoxycarbonylamino)propylphosphonate were synthesized from the respective diethyl [-(1-phenylethyl)]-1-benzylamino-2,3-epiiminopropylphosphonates via opening the aziridine ring with trimethylsilyl azide (TMSN) followed by hydrogenolysis in the presence of di--butyl dicarbonate (BocO). [-(1-phenylethyl)]-1-benzylamino-2,3-epiiminopropylphosphonates (1,2,1')- and (1,2,1')- were smoothly transformed into diethyl 3-acetoxy-1-benzylamino-2-[-(1-phenylethyl)amino]propylphosphonates (1,2,1')- and (1,2,1')-, respectively by the opening of the aziridine ring with acetic acid. Transformations of [-(1-phenylethyl)]-1-benzylamino-2,3-epiiminopropylphosphonates (1,2,1')- and (1,2,1')- into diethyl 3-acetoxy-1-benzylamino-2-[(1-phenylethyl)amino]propylphosphonates (1,2,1')- and (1,2,1')- were accompanied by the formation of ethyl {1-(-benzylacetamido)-3-hydroxy-2-[(1-phenylethyl)amino]propyl}phosphonate (1,2,1')- and (1,2,1')- and 3-(-benzylacetamido)-4-[-(1-phenylethyl)]amino-1,2-oxaphospholane (3,4,1')- and (3,4,1')- as side products. Diethyl (1,2)-, (1,2)-, (1,2)- and (1,2)-3-acetoxy-1,2-di(--butoxycarbonylamino)propylphosphonates - were obtained from the respective 3-acetoxy-1-benzylamino-2-[-(1-phenylethyl)amino]propylphosphonates - by hydrogenolysis in the presence of BocO.