Abstract: A process for production of cyclopropyl-fused pyrrolidine-based inhibitors of dipeptidyl peptidase IV is provided which employs a BOC-protected amine of the structure prepared by subjecting an acid of the structure to reduce amination by treating the acid with ammonium formate, nicotinamide adenine dinucleotide, dithiothreitol and partially purified phenylalanine dehydrogenase/formate dehydrogenase enzyme concentrate (PDH/FDH) and without isolating treating the resulting amine of the structure 2 with di-tert-butyl dicarbonate to form the BOC-protected amine.

Abstract: A process for production of cyclopropyl-fused pyrrolidine-based inhibitors of dipeptidyl peptidase IV is provided which employs a BOC-protected amine of the structure prepared by subjecting an acid of the structure to reduce amination by treating the acid with ammonium formate, nicotinamide adenine dinucleotide, dithiothreitol and partially purified phenylalanine dehydrogenase/formate dehydrogenase enzyme concentrate (PDH/FDH) and without isolating treating the resulting amine of the structure 2 with di-tert-butyl dicarbonate to form the BOC-protected amine

Abstract: A process for production of cyclopropyl-fused pyrrolidine-based inhibitors of dipeptidyl peptidase IV is provided which employs a BOC-protected amine of the structure prepared by subjecting an acid of the structure to reduce amination by treating the acid with ammonium formate, nicotinamide adenine dinucleotide, dithiothreitol and partially purified phenylalanine dehydrogenase/formate dehydrogenase enzyme concentrate (PDH/FDH) and without isolating treating the resulting amine of the structure 2 with di-tert-butyl dicarbonate to form the BOC-protected amine.

Abstract: The present invention relates to a process for preparing (2R,3S)-1-halo-2-hydroxy-3-(protected)amino-4-substituted butane comprising contacting a mutagenized Rhodococcus erythropolis having ATCC deposit no. PTA-6648 with (3S)-1-halo-2-oxo-3-(protected)amino-4-substituted butane substrate. The present invention also relates to a process comprising mixing (2R,3S)-1-halo-2-hydroxy-3-(protected)amino-4-substituted butane with at least one base in the presence of at least one solvent to produce a reaction mixture containing (2R,3S)-1,2-epoxy-3-(protected)amino-4-substituted butane. The present invention further relates to a process comprising crystallizing the (2R,3S)-1,2-epoxy-3-(protected)amino-4-substituted butane out of the reaction mixture by concurrently adding water and the reaction mixture together. The present invention is also directed to a mutagenized Rhodococcus erythropolis having ATCC deposit no. PTA-6648.

Abstract: A process for production of cyclopropyl-fused pyrrolidine-based inhibitors of dipeptidyl peptidase IV is provided which employs a BOC-protected amine of the structure prepared by subjecting an acid of the structure to reduce amination by treating the acid with ammonium formate, nicotinamide adenine dinucleotide, dithiothreitol and partially purified phenylalanine dehydrogenase/formate dehydrogenase enzyme concentrate (PDH/FDH) and without isolating treating the resulting amine of the structure 2 with di-tert-butyl dicarbonate to form the BOC-protected amine.

Abstract: A process for production of cyclopropyl-fused pyrrolidine-based inhibitors of dipeptidyl peptidase IV is provided which employs a BOC-protected amine of the structure prepared by subjecting an acid of the structure to reduce amination by treating the acid with ammonium formate, nicotinamide adenine dinucleotide, dithiothreitol and partially purified phenylalanine dehydrogenase/formate dehydrogenase enzyme concentrate (PDH/FDH) and without isolating treating the resulting amine of the structure 2 with di-tert-butyl dicarbonate to form the BOC-protected amine.

Abstract: The present invention relates to a process for preparing (2R,3S)-1-halo-2-hydroxy-3-(protected)amino-4-substituted butane comprising contacting a mutagenized Rhodococcus erythropolis having ATCC deposit no. PTA-6648 with (3S)-1-halo-2-oxo-3-(protected)amino-4-substituted butane substrate. The present invention also relates to a process comprising mixing (2R,3S)-1-halo-2-hydroxy-3-(protected)amino-4-substituted butane with at least one base in the presence of at least one solvent to produce a reaction mixture containing (2R,3S)-1,2-epoxy-3-(protected)amino-4-substituted butane. The present invention further relates to a process comprising crystallizing the (2R,3S)-1,2-epoxy-3-(protected)amino-4-substituted butane out of the reaction mixture by concurrently adding water and the reaction mixture together. The present invention is also directed to a mutagenized Rhodococcus erythropolis having ATCC deposit no. PTA-6648.

Abstract: An enzymatic ammonolysis process is provided for the preparation of intermediates used in preparing dipeptidyl peptidase IV inhibitors wherein the enzyme Candida antarctica lipase-B is used to catalyze the ammonolysis process.

Abstract: The present invention relates to a process for preparing (2R,3S)-1-halo-2-hydroxy-3-(protected)amino-4-substituted butane comprising contacting a mutagenized Rhodococcus erythropolis having ATCC deposit no. PTA-6648 with (3S)-1-halo-2-oxo-3-(protected)amino-4-substituted butane substrate. The present invention also relates to a process comprising mixing (2R,3S)-1-halo-2-hydroxy-3-(protected)amino-4-substituted butane with at least one base in the presence of at least one solvent to produce a reaction mixture containing (2R,3S)-1,2-epoxy-3-(protected)amino-4-substituted butane. The present invention further relates to a process comprising crystallizing the (2R,3S)-1,2-epoxy-3-(protected)amino-4-substituted butane out of the reaction mixture by concurrently adding water and the reaction mixture together. The present invention is also directed to a mutagenized Rhodococcus erythropolis having ATCC deposit no. PTA-6648.

Abstract: An enzymatic ammonolysis process is provided for the preparation of intermediates used in preparing dipeptidyl peptidase IV inhibitors wherein the enzyme Candida antarctica lipase-B is used to catalyze the ammonolysis process.

Abstract: Provided is a method of resolving a racemic mixture of a compound of formula I to obtain a desired enantiomer: wherein Ar is C6 or C10 aromatic group that can be substituted with H, C1 to C6 alkyl, trifluoromethyl or halo, R5 is halo or —S—R1, wherein R1 is H or acetyl, and R2 is H or C1 to C6 alkyl, the method comprising: reacting a compound of formula I wherein the compound is an ester whereby R2 is C1 to C6 alkyl with a lipase derived from Mucor meihei to stereoselectively hydrolyze the ester bond to produce an acid; and isolating the acid, wherein the reaction is conducted in a solvent comprising 80% to 98% v/v % organic phase and a residue of water phase (which can be buffered).

Abstract: A method of making didanosine (ddI) including the steps of: (a) obtaining an enzyme expressing ddA deaminase activity; (b) immobilizing the enzyme onto an insoluble support; (c) contacting the enzyme with a dideoxyadenosine (ddA) solution of at least about 4% weight volume ddA in water for a time and under conditions to produce a ddI solution; and (d) isolating the ddI from the ddI solution. Optionally, the ddI mother liquor is reused in subsequent runs to improve yield.

Abstract: Provided is a method of resolving a racemic mixture of a compound of formula I to obtain a desired enantiomer: 1

Abstract: Provided is a method of resolving a racemic mixture of a compound of formula I to obtain a desired enantiomer: wherein Ar is C6 or C10 aromatic group that can be substituted with H, C1 to C6 alkyl, trifluoromethyl or halo, R5 is halo or —S—R1, wherein R1 is H or acetyl, and R2 is H or C1 to C6 alkyl, the method comprising: reacting a compound of formula I wherein the compound is an ester whereby R2 is C1 to C6 alkyl with a lipase derived from Mucor meihei to stereoselectively hydrolyze the ester bond to produce an acid; and isolating the acid, wherein the reaction is conducted in a solvent comprising 80% to 98% v/v % organic phase and a residue of water phase (which can be buffered).

Abstract: Provided is a method of resolving a racemic mixture of a compound of formula I to obtain a desired enantiomer: 1

Abstract: An improved process suitable for large-scale production of 2',3'-didehydro-3'-deoxythymidine (d4T) and close analogs is disclosed. The improved process yields d4T in high yield and purity without the use of hazardous reactions or reagents and incorporates several process improvements important on a large scale including a novel purification step involving the isolation of a d4T.N-methylpyrrolidinone solvate.

Abstract: There is provided a novel and efficient stereoselective total synthesis of epipodophyllotoxin and related epipodophyllotoxin compounds of the and present invention ##STR1## wherein R.sup.1 and R.sup.2 each are independently hydrogen or (lower)alkoxy, or R.sup.1 ll and R.sup.2, taken together, is methylenedioxy; R.sup.4 and R.sup.6 each are independently hydrogen or (lower)alkoxy; and R.sup.5 is hydrogen or a phenol-protecting group; or an acid addition salt thereof. The present ivnention also provides novel intermediates and processes for the preparation of said intermediates, which are then converted into known antineoplastic agents.

Abstract: There is provided a novel and efficient stereoselective total synthesis of epiodophyllotoxin and related epipodophyllotoxin compounds of the general formula ##STR1## wherein R.sup.1 and R.sup.2 are independently hydrogen or (lower)-alkoxy, or R.sup.1 and R.sup.2, taken together, is methylenedioxy; R.sup.4 and R.sup.6 each are independently hydrogen or (lower) alkoxy; and R.sup.5 is hydrogen or a phenol-protecting group; or an acid addition salt thereof. The present invention also provides novel intermediates and processes for the preparation of said intermediates, which are then converted into known antineoplastic agents.

Abstract: There is provided a novel and efficient stereoselective total synthesis of epipodophyllotoxin and related epipodophyllotoxin compounds of the general formula ##STR1## wherein R.sup.1 and R.sup.2 each are independently hydrogen or (lower)alkoxy, or R.sup.1 and R.sup.2, taken together, is methylenedioxy; R.sup.4 and R.sup.6 each are independently hydrogen or (lower)alkoxy; and R.sup.5 is hydrogen or a phenol-protecting group; or an acid addition salt thereof. The present invention also provides novel intermediates and processes for the preparation of said intermediates, which are then converted into known antineoplastic agents.

Abstract: There is provided a novel and efficient stereoselective total synthesis of epipodoplyllotoxin and related epipodophyllotoxin compounds of the general formula ##STR1## wherein R.sup.1 and R.sup.2 each are independently hydrogen or (lower)-alkoxy, or R.sup.1 and R.sup.2, taken together, is methylenedioxy; R.sup.4 and R.sup.6 each are independently hydrogen or (lower)alkoxy; and R.sup.5 is hydrogen or a phenol-protecting group; or an acid addition salt thereof. The present invention also provides novel intermediates and processes for the preparation of said intermediates, which are then converted into known antineoplastic agents.