G.d. Searle & Company

The Nutrasweet Company

Monsanto Company

Searle & Co.

Mike G Scaros

Roy W Grabner

Bryan H Landis

Michael L Prunier

Ping T Wang

Indra Prakash

Richard M Weier

Ish K Khanna

James R Behling

Hugh L Dryden, Jr

John R Medich

Payman N Farid

Mike Prunier

Rick J Rutter

Joseph J Wieczorek

John H Dygos

Kurt L Wachholder

Kathleen T McLaughlin

Thomas R Kowar

Gatis Plume

Christine M V Moore

Richard J Salzmann

Vladislav Orlovski

Thomas J Telinski

John P Westrich

Richard J Rutter

Processes for using modified catalysts with improved functionality in the production of neotame are disclosed. The modified catalysts surprisingly have been found to improve the selectivity over conventional catalysts and to reduce the level of certain impurities in neotame production processes.

Catalyst modification to enhance neotame production

The invention is a process for producing N-substituted glucamines, a process for oxidizing an N-substituted glucamine with an oxidizing microbe or extract thereof, and a process for oxidizing an N-substituted glucamine with an oxidizing microbe or extract thereof and reducing the oxidized N-substituted glucamine to an N-substituted-1-deoxynojirimycin. In addition, a one pot process for producing N-substituted-1-deoxynojirimycin from -glucose is disclosed.

Salt forms of 6-n-butylamino-6-deoxy-&agr;-L-sorbofuranose

The synthesis of N-&lsqb;N-(3,3-dimethylbutyl)-L-&agr;-aspartyl&rsqb;-L-phenylalanine 1-methyl ester via conversion under reducing conditions of novel imidazolidinone(s) is disclosed.

Method for the preparation of N-neohexyl-&agr;-aspartyl-L-phenylalanine methyl ester from imidazolidin-4-one intermediates

N-&lsqb;N-(3,3-dimethylbutyl)-L-&agr;-aspartyl&rsqb;-L-phenylalanine 1-methyl ester is produced by reductive alkylation and crystallization/isolation in methanol and water. The production method is efficient and low cost, as compared with conventional N-&lsqb;N-(3,3-dimethylbutyl)-L-&agr;-aspartyl&rsqb;-L-phenylalanine 1-methyl ester synthesis and results in high purity N-&lsqb;N-(3,3-dimethylbutyl)-L-&agr;-aspartyl&rsqb;-L-phenylalanine 1-methyl ester.

Synthesis of N-(N-(3,3-dimethylbutyl)-L-&agr;-aspartyl)L-phenylalanine1-methyl ester by reductive alkylation and crystallization/ isolation in aqueous methanol

The invention is a process for producing N-substituted glucamines, a process for oxidizing an N-substituted glucamine with an oxidizing microbe or extract thereof, and a process for oxidizing an N-substituted glucamine with an oxidizing microbe or extract thereof and reducing the oxidized N-substituted glucamine to an N-substituted-1-deoxynojirimycin. In addition, a one pot process for producing N-substituted-1-deoxynojirimycin from D-glucose is disclosed.

Process for microbially oxidizing N-substituted glucamines

A process for producing N-substituted amino compounds, a process for oxidizing an N-substituted amino compound with a microbe, or cell fragment or cell free extract thereof, and a process for oxidizing an N-substituted amino compound with a microbe, or cell fragment or cell free extract thereof and reducing the oxidized N-substituted amino compound to N-substituted-polyhydroxy piperidines based on N-substituted mannosamines, allosamines and altrosamines, N-substituted polyhydroxy pyrrolidines, and N-substituted polyhydroxy azetidines. In addition, a one pot process for producing N-substituted-polyhydroxy piperidines based on N-substituted mannosamines, allosamines and altrosamines, N-substituted polyhydroxy pyrrolidines, and N-substituted polyhydroxy azetidines from the respective sugar is disclosed. A second embodiment comprises novel compositions of N-substituted-amino-6-deoxy-2-ketohexuloses based on mannose, allose and altrose, N-substituted-amino-5-deoxy-2-ketopentuloses and 4-(N-substituted)-amino-1,3-dihydroxy-2-butanones.

Process for producing N-substituted polyhydroxy nitrogen-containing

Process for producing N-substituted-1-deoxynojirimycin

The present invention relates to a novel process for the preparation of heterocyclic alkylamide derivatives having the following formula: ##STR1## and the pharmaceutically acceptable acid addition salt thereof wherein X represents halo, alkyl having 1 to 6 carbon atoms, hydrido, trifluoromethyl, phenyl, or lower alkoxy having 1 to 6 carbon atoms; Y represents the group --CN or --CONH.sub.2 ; R.sub.2 represents alkyl having 1 to 6 carbon atoms; R.sub.3 represents acetyl, benzoyl, phenacetyl or trifluoroacetyl; m is the integer 1 or 2 and n is an integer from 1 to 3 inclusive; which comprises alkylating an aminoalkanol using a benzaldehyde/aminoalkanol/ketone mixture in the presence of a platinum catalyst to give an alkyl substituted phenylmethylaminoalkanol; halogenating the alkanol using a halogenating agent to give a haloalkyl alkylbenzenemethanamine salt; treating the salt with substituted phenyl piperidinealkanenitrile or substituted phenyl pyrrolidinealkanenitrile in the presence of base and dimethyl sulfoxide to give a substituted phenyl substituted aminoalkyl piperidinealkanenitrile or substituted aminoalkyl pyrrolidinealkanenitrile; hydration of the nitrile to give the corresponding amide; and N-debenzylation of the amide followed by acetylation to give the compounds of formula I wherein Y is --CONH.sub.2.

Process for the preparation of heterocyclic alkylamide derivatives

Process for producing n-substituted polyhydroxy nitrogen-containing

A process for the preparation of 1,2-O-(1-methylethylidine)-.alpha.-L-sorbofuranose and 6-(n-substituted amino)-6-deoxy-1,2-O-(1-methylethylidine)-.alpha.-L-sorbofuranose and derivatives of the formula: ##STR1## wherein R' is benzyl or R, wherein R is hydrogen, alkyl of 1 to 13 carbon atoms, and aralkyl wherein alkyl is a lower alkyl of 2 to 6 carbon atoms and aryl is phenyl, unsubstituted or substituted with lower alkyl of 1 to 6 carbon atoms, halo, lower alkoxy of 1 to 4 carbon atoms or thio lower alkyl of 1 to 4 carbon atoms by the steps of: treating L-sorbose with 2,2-dimethoxy propane to yield 1,2:4,6-di-O-(1-methylethylidine)-.alpha.-L-sorbofuranose; treating the compound with sulfuric acid in a solvent to produce 1,2-O-(1-methylethylidine)-.alpha.-L-sorbofuranose; and consecutively treating with sulfonyl chloride and with an amine to yield 6-(substituted amino)-6-deoxy- 1,2-O-(1-methylethylidine)-.alpha.-L-sorbofuranose.

Process for the preparation of

A process for the preparation of 1,5-(alkylimino)-1,5-dideoxy-D-glucitol and derivatives of the formula: ##STR1## wherein R is hydrogen, alkyl of 1 to 13 carbon atoms, and aralkyl wherein alkyl is a lower alkyl of 2 to 6 carbon atoms, and aryl is phenyl, unsubstituted or substituted with lower alkyl of 1 to 6 carbon atoms, halo, lower alkoxy of 1 to 4 carbon atoms or thio lower alkyl of 1 to 4 carbon atoms by the steps of: treating L-sorbose with 2,2-dimethoxypropane to yield 1,2:4,6-di-O-(1-methylethylidene)-.alpha.-L-sorbanose; treating the compound with sulfuric acid in a solvent to produce 1,2-O-(1-methylethylidine)-.alpha.-L-sorbofuranose; consecutively treating with sulfonyl chloride and with an amine to yield 6-(substituted amino)-6-deoxy-1,2-O-(1-methylethylidine)-.alpha.-L-sorbofuranose; adsorbing the compound on an ion exchange resin and hydrogenating to produce compounds of the above formula.

Process for the preparation of 1,5-(alkylimino)-1,5-dideoxy-D-glucitol

The present invention is concerned with an improved process for the preparation of trimethylsulfoxonium bromide. The improvement in the process comprises the addition of a scavenger to the reaction mixture of dimethyl sulfoxide and methyl bromide.

Process for the preparation of trimethylsulfoxonium bromide

A new process for the preparation of 17.beta.-hydroxy-3-oxo-17.alpha.-pregn-4-ene-21-carboxylic acid .gamma.-lactone is described herein. The process makes use of androst-4-ene-3,17-dione as the starting material and 17.alpha.-ethynyl-17.beta.-hydroxyandrost-4-en-3-one as an early intermediate.

Growing community of inventors

Arlington Heights, IL, United States of America

Mike G Scaros