Synthesis of Enantiomerically Enriched Protected 2-Amino-, 2,3-Diamino- and 2-Amino-3-Hydroxypropylphosphonates.

Simple and efficient strategies for the syntheses of enantiomerically enriched functionalized diethyl 2-amino-, 2,3-diamino- and 2-amino-3-hydroxypropylphosphonates have been developed starting from, respectively, -protected (aziridin-2-yl)methylphosphonates, employing a regioselective aziridine ring-opening reaction with corresponding nucleophiles. Diethyl ()- and ()-2-(-Boc-amino)propylphosphonates were obtained via direct regiospecific hydrogenolysis of the respective enantiomer of ()- and ()--Boc-(aziridin-2-yl)methylphosphonates. N-Boc-protected ()- and ()-2,3-diaminopropylphosphonates were synthesized from ()- and ()--Bn-(aziridin-2-yl)methylphosphonates via a regiospecific ring-opening reaction with neat trimethylsilyl azide and subsequent reduction of ()- and ()-2-(-Boc-amino)-3-azidopropylphosphonates using triphenylphosphine.

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.

-(1-Phenylethyl)aziridine-2-carboxylate esters in the synthesis of biologically relevant compounds.

Since Garner's aldehyde has several drawbacks, first of all is prone to racemization, alternative three-carbon chirons would be of great value in enantioselective syntheses of natural compounds and/or drugs. This review article summarizes applications of -(1-phenylethyl)aziridine-2-carboxylates, -carbaldehydes and -methanols in syntheses of approved drugs and potential medications as well as of natural products mostly alkaloids but also sphingoids and ceramides and their 1- and 3-deoxy analogues and several hydroxy amino acids and their precursors. Designed strategies provided new procedures to several drugs and alternative approaches to natural products and proved efficiency of a 2-substituted -(1-phenylethyl)aziridine framework as chiron bearing a chiral auxiliary.