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

ABSTRACT: All possible isomers of 1,2,3-tri(N-tert-butoxycarbonylamino)propylphosphonate 6 were synthesized from the respective diethyl [N-(1-phenylethyl)]-1-benzylamino-2,3-epiiminopropylphosphonates 5 via opening the aziridine ring with trimethylsilyl azide (TMSN₃) followed by hydrogenolysis in the presence of di-tert-butyl dicarbonate (Boc₂O). [N-(1-phenylethyl)]-1-benzylamino-2,3-epiiminopropylphosphonates (1R,2R,1'S)-5a and (1S,2S,1'R)-5c were smoothly transformed into diethyl 3-acetoxy-1-benzylamino-2-[N-(1-phenylethyl)amino]propylphosphonates (1R,2R,1'S)-9a and (1S,2S,1'R)-9c, respectively by the opening of the aziridine ring with acetic acid. Transformations of [N-(1-phenylethyl)]-1-benzylamino-2,3-epiiminopropylphosphonates (1S,2R,1'S)-5b and (1R,2S,1'R)-5d into diethyl 3-acetoxy-1-benzylamino-2-[(1-phenylethyl)amino]propylphosphonates (1S,2R,1'S)-9b and (1R,2S,1'R)-9d were accompanied by the formation of ethyl {1-(N-benzylacetamido)-3-hydroxy-2-[(1-phenylethyl)amino]propyl}phosphonate (1S,2R,1'S)-10b and (1R,2S,1'R)-10d and 3-(N-benzylacetamido)-4-[N-(1-phenylethyl)]amino-1,2-oxaphospholane (3S,4R,1'S)-11b and (3R,4S,1'R)-11d as side products. Diethyl (1R,2R)-, (1S,2S)-, (1S,2R)- and (1R,2S)-3-acetoxy-1,2-di(N-tert-butoxycarbonylamino)propylphosphonates 7a-7d were obtained from the respective 3-acetoxy-1-benzylamino-2-[N-(1-phenylethyl)amino]propylphosphonates 9a-9d by hydrogenolysis in the presence of Boc₂O.

SUBMITTER: Trocha A 

PROVIDER: S-EPMC6864986 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature