Wisconsin Alumni Research Foundation

Miles Laboratories, Inc.

Suntory Limited

Sigma-tau Industrie Farmaceutiche Riunite S.p.a.

Other

Charles J Sih

William G Biddlecom

Warren D Woessner

Henry Clifford Arndt

Harold C Kluender

George Peter Peruzzotti

James B Heather

Chien-An Chen

Manrico Bernardini

Stuart Shapiro

The present invention provides a method of preparing conjugated polyunsaturated fatty acids wherein the fatty acid substrate has two or more double bonds and diallylic hydrogens by one or more treatments with a superstrong base. Isomeric purity can be accomplished with a further step of enzymatic hydrolysis and separation.

Synthesis of conjugated polyunsaturated fatty acids

A process for preparing optically active 1-substituted-3-hydroxy-1-butene or its derivatives of formula (II) or (III) ##STR1## is disclosed. The process comprises treating an ester derivative of racemic 1-substituted-3-hydroxy-1-butene of formula (I), ##STR2## wherein R.sub.1 is a substituted or unsabstituted alkyl, aryl, alkoxy, or aryloxy group, and R.sub.2 is a hydrogen atom, halogen atom, an alkyl, aryl, alkoxy or aryloxy group, or a substituted or unsabstituted alkylsulfonyloxy, arylsulfonyloxy, alkylthio, or arylthio group. The process can produce a desired optically active alcohol or acyl-protected compound at a high yield and a high selectivity under mild conditions by the treatment of the substrate with a lipase. In particular, when R.sub.1 =methyl and R.sub.2 =halogen or phenylthio, use of Lipase AK, P-30 or K-10 gives high enantiomeric purity.

Process for preparing optically active alpha-hydroxyalkene derivatives

A non-enzymatic stereoselective cyclization of .beta.-NAD.sup.+ to yield cyclic ADP-ribose (cADPR). By heating .beta.-NAD.sup.+ in an anhydrous solvent in the presence of a metal halide and a nonnucleophilic base, cADPR was obtained as the sole cyclic isomer in yields as high as 28%. .alpha.-NAD was also converted into cADPR under the same reaction conditions. Several analogs of cADPR have also been synthesized and some of these analogs have a greater Ca.sup.++ release activity than cADPR itself.

Cyclic ADP-ribose and analogs

A process is provided for preparing an L-.alpha.-amino acid from a 5(4H)-oxazolone precursor. The precursor is subjected to a two-step process sequence in which the precursor is first contacted with a methanolytically active lipase in the presence of methanol in a non-polar solvent to enantioselectively solvolyze the precursor and produce an intermediate optically active methyl ester of the desired .alpha.-amino acid. This ester is then contacted with a protease in the presence of water to enantioselectively cleave the ester and accomplish an enzymatic kinetic resolution to prepare the product L-.alpha.-amino acid in high optical purity.

Method for preparing L-alpha-amino acids

A process is described for stereospecifically hydrating crotonobetaine to L-(-)-carnitine via the action of an enzyme produced by four new strains of Proteus mirabilis (NRRL B-18480, NRRL B-18481, NRRL B-18482, and NRRL B-18483) in biotransformation media containing from 10 to 12% (w/v) crotonobetaine inner salt.

Biocatalytic process for the production of L-(-)-carnitine from

The invention relates to a method for enzymatically producing directly optically-active amino acid derivatives in high optical purity from oxazolone precursors. Thus, such a precursor is subjected to the presence of a catalytically effective amount of a selected enzyme in a mutual solvent. The cyclic precursor is enantioselectively cleaved by hydrolysis. Subsequently, the desired optically-active amino acid derivative is recovered. A preferred cyclic precursor is a 5(4H)-oxazolone compound and a preferred enzyme is a lipase. Either aqueous or organic solvent media can be used.

Method for preparing optically-active amino acid derivatives

A process for preparing optically active 1-substituted-3-hydroxybutane or its derivatives of formula (II) or (III) ##STR1## comprising treating an ester derivative of racemic 1-substituted-3-hydroxybutane of formula (I), ##STR2## wherein R.sub.1 is chloromethyl group or methyl group and R.sub.2 is p-toluenesulfonyloxy group or phenylthio group, provided that when R.sub.1 is methyl group R.sub.2 is not p-toluenesulfonyloxy group, with a lipase derived from the genus Pseudomonas.

Process for preparing optically active 3-hydroxybutane derivatives using

The invention relates to a method for microbiologically resolving racemic 2,3-o-substituted glycerol esters to obtain optically activated 2,3-o-substituted glycerol with remaining esters also being optically active.

Process for preparing optically-active glycerol ketal derivatives

The invention provides a process for preparing optically-active 2,2'-dihydroxy-1,1'-binaphthyl by subjecting esters of (+) 2,2'-dihydroxy-1,1'-binaphthyl to the enantioselective hydrolytic enzymatic action of microorganisms of the orders Moniliales and Mucorales.

Process for preparing optically active 2,2'-dihydroxy-1,1'-binaphthyl

The invention provides a method for enhancing the degradation of the side chain of sterols possessing branched chains at C-24 utilizing microbiological means by including an exogenous source of bicarbonate ion (HCO.sub.3 --) in the medium in which the degradation is being carried out.

Process for preparing steroids

A process for preparing L-carnitine which comprises exposing .gamma.-substituted acetoacetic acid esters or amides to the fermentative enzymatic action of a microorganism which elaborates L-.beta.-hydroxyacyl CoA dehydrogenase [EC 1.1.1.35] , recovering the resulting, optically active corresponding .gamma.-substituted-.beta.-hydroxybutyric acid derivative and converting said derivative to L-carnitine. An improvement in the process is also disclosed which comprises reacting a 4-chloro-3(R)-hydroxybutyrate with sodium iodide or bromide to produce the corresponding 4-iodo- or 4-bromo-3(R)-hydroxybutyrate, converting the 4-iodo- or 4-bromo-3(R)-hydroxybutyrate to the trimethylamino-3(R)-hydroxybutyrate salt, then converting the trimethylamino-3(R)-hydroxybutyrate salt into L-carnitine. Novel chemical intermediates prepared in the processes are also disclosed.

Process for preparing L-carnitine and chemical intermediates employed

A process for preparing L-carnitine which comprises exposing .gamma.-substituted acetoacetic acid esters or amides to the fermentative enzymatic action of a microorganism which elaborates oxido-reductase enzymes, recovering the resulting, optically active, corresponding .gamma.-substituted-.beta.-hydroxybutyric acid derivative and converting said derivative to L-carnitine.

Process for preparing a compound for use in the production of L-carnitine

The present invention relates to processes for preparing optically-active 4-amino-3-hydroxybutyric acid by asymmetrically cleaving one of the enantiotopic ester groupings of 3-hydroxyglutaric diester by the action of microbial enzymes to obtain a chiral monoacid which is readily converted into optically-active 4-amino-3-hydroxybutyric acid by chemical means.

Process for preparing optically-active 4-amino-3-hydroxybutyric acid

The invention discloses a method for preparing optically active bifunctional synthons useful in synthesizing natural isoprenodis by resolving racemic substituted aryloxy-.alpha.-alkyl esters through the hydrolytic action of microorganisms selected from the orders Endomycetales and Eubacteriales.

Growing community of inventors

Madison, WI, United States of America

Charles J Sih