A chemo-enzymatic synthesis of optically active 1,1-diethoxyethyl(aminomethyl)phosphinates: useful chiral building blocks for phosphinyl dipeptide isosteres

The kinetic resolution of 1,1-diethoxyethyl(hydroxymethyl)phosphinate possessing chirality at the phosphorus atom was achieved via a lipase-catalyzed acylation. The product was transformed into the corresponding imine, which in turn is a useful starting material for the preparation of phosphinyl dipeptide isosteres.

Figure optionsDownload as PowerPoint slide

(RP)-Ethyl 1,1-diethoxyethyl(hydroxymethyl)phosphinateC9H21O5PEe >99%[α]D20=-11.8 (c 0.4, CHCl3)Source of chirality: lipase AKAbsolute configuration: (RP)

(SP)-Ethyl acetoxymethyl(1,1-diethoxyethyl)phosphinateC11H23O6PEe = 77%[α]D20=+6.1 (c 1.2, CHCl3)Source of chirality: lipase AKAbsolute configuration: (SP)

(RP)-[(1,1-Diethoxyethyl)(ethoxy)phosphoryl]methyl 4-methylbenzenesulfonateC16H27O7PSEe >99%[α]D20=-17.7 (c 0.6, CHCl3)Source of chirality: lipase AKAbsolute configuration: (RP)

(RP)-Ethyl (benzylamino)methyl(1,1-diethoxyethyl)phosphinateC16H28NO4PEe >99%[α]D20=-20.8 (c 0.7, CHCl3)Source of chirality: lipase AKAbsolute configuration: (RP)

(RP)-Ethyl 1,1-diethoxyethyl{[(diphenylmethylene)amino]methyl}phosphinateC22H30NO4PEe >99%[α]D20=-17.2 (c 0.8, CHCl3)Source of chirality: lipase AKAbsolute configuration: (RP)