Hoffmann-la Roche Inc.

John William Scott

Gabriel G Saucy

David Richard Parrish

Leo Berger

Willy Leimgruber

Andrew D Batcho

Donald H Valentine, Jr

Urs Oskar Hengartner

Alfred J Corraz

Andor Furst

Werner Meier

Ludwig Labler

Paul Buchschacher

The preparation of racemic and optically pure tryptophans is described. The D-enantiomers of the 6-substituted compounds possess a potent sweetening capability. Novel intermediates are also disclosed.

Pyrroles and pyrrolidines

Novel syntheses of tryptophans

A process for preparing 6-chloro-.alpha.-methylcarbazole-2-acetic acid and esters thereof by the steps of:

Process of making a carbazole acetic acid

6-Chloro-1,2,3,4-tetrahydrocarbazole-2-one

A process for the preparation of 6-chloro-.alpha.-methylcarbazole-2-acetic acid from 6-chloro-.alpha.-hydroxy-.alpha.-methylcarbazole-2-acetic acid and/or 6-chloro-.alpha.-methylene-2-carboxylic acid, is described. The preparation of intermediates, such as, 6-chloro-.alpha.-hydroxy-.alpha.-methylcarbazole-2-acetic acid and lower alkyl carbazole-2-oxalate, inter alia, is also described.

Carbazole acetic acid derivatives

Hydroxy methyl carbazole acetic acid and esters

A process for preparing 6-chloro-.alpha.-methylcarbazole-2-acetic acid and esters thereof by the steps of: (a) reacting 6-chloro-1,2,3,4-tetrahydrocarbazole-2-one with a trialkyl-.alpha.-methylphosphonoacetate to yield the corresponding 3,4-dihydro-.alpha.-methylcarbazole-2-acetic acid ester; and (b) aromatizing the reaction product of step (a), prior to or after saponification, to yield, respectively, 6-chloro-.alpha.-methylcarbazole-2-acetic acid or ester, is described. Additionally, there are described 6-chloro-1,2,3,4-tetrahydrocarbazole-2-one useful as an intermediate, and dihydrocarbazoles useful as intermediates and/or as anti-inflammatory and antirheumatic agents.

Dihydrocarbazole acetic acid and esters thereof

Lower alkyl esters of 2-formamido-3(4,5,6 or 7-methyl substituted-3-indolyl)-2-carbalkoxy propionic acid which are useful as intermediates for tryptophane sweetners.

Lower alkyl esters of .alpha.-formamido,.alpha.-carbalkoxy tryptophans

Treatment of de-A steroids with a methylation agent at extremely low temperatures, i.e., below -50.degree. C. produces corresponding 10.beta.-methyl-.DELTA..sup.9(11) -deA steroids with a high 10.beta. to 10.alpha. isomer ratio. A number of the product 10.beta.-methyl-.DELTA..sup.9(11) -deA steroids are novel compounds. They are useful as intermediates in the synthesis of known medicinally valuable steroids.

Methylation of de-A steroids

The intermediates and processes of this invention provide a new synthetic route for the preparation of pharmaceutically valuable 19-norsteroids. Further, the intermediates and processes of the invention provide a route for the preparation of pharmaceutically valuable estrones. The present invention provides a facile total synthesis of 19.beta.-alkyl-C/D-trans-steroidal materials. This desirable result is obtained via a unique asymmetric induction followed by subsequent stereo-specific reaction steps. As a precursor to the steroidal Ring A, a 3,5-disubstituted-4-isoxazolylmethylene group is employed in this synthesis.

Intermediates in the total synthesis employing substituted isoxazole

Synthesis of tryptophans

The novel intermediates and processes of this invention provide a new synthetic route for the preparation of pharmaceutically valuable 19-norsteroids. Further, the intermediates and processes of the invention provide a novel route for the preparation of pharmaceutically valuable estrones. The present invention provides a facile total synthesis of 19.beta.-alkyl-C/D-trans-steroidal materials. This desirable result is obtained via a unique asymmetric induction followed by subsequent stereospecific reaction steps. As a precursor to the steroidal Ring A, a 3,5-disubstituted-4-isoxazolylmethylene group is employed in this synthesis.

Total steroid synthesis employing substituted isoxazole derivatives

The (6-hydroxy-chroman-2-yl) acetic or carboxylic acid derivatives useful as antioxidants and a method for preparing these derivatives from hydroquinones and intermediates in this synthesis as well as the use of these derivatives as intermediates in the preparation of optically active alpha-tocopherol.

Growing community of inventors

Upper Montclair, NJ, United States of America

John William Scott