Patents by Inventor Charles J. Sih
Charles J. Sih has filed for patents to protect the following inventions. This listing includes patent applications that are pending as well as patents that have already been granted by the United States Patent and Trademark Office (USPTO).
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Patent number: 6316645Abstract: 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.Type: GrantFiled: October 20, 1998Date of Patent: November 13, 2001Assignee: Wisconsin Alumni Research FoundationInventors: Charles J. Sih, Chien-An Chen
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Patent number: 5637500Abstract: 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.Type: GrantFiled: September 26, 1994Date of Patent: June 10, 1997Assignee: Suntory LimitedInventor: Charles J. Sih
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Patent number: 5608047Abstract: 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.Type: GrantFiled: March 15, 1995Date of Patent: March 4, 1997Assignee: Wisconsin Alumni Research FoundationInventor: Charles J. Sih
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Patent number: 5541080Abstract: 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.Type: GrantFiled: May 28, 1993Date of Patent: July 30, 1996Assignee: Wisconsin Alumni Research Fdn.Inventor: Charles J. Sih
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Patent number: 5300430Abstract: 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.Type: GrantFiled: January 7, 1993Date of Patent: April 5, 1994Assignee: Sigma-Tau Industrie Farmaceutiche Riunite S.p.A.Inventors: Stuart Shapiro, Manrico Bernardini, Charles J. Sih
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Patent number: 5219731Abstract: 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.Type: GrantFiled: November 1, 1991Date of Patent: June 15, 1993Assignee: Wisconsin Alumni Research FoundationInventor: Charles J. Sih
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Patent number: 5128264Abstract: 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.Type: GrantFiled: August 13, 1990Date of Patent: July 7, 1992Assignee: Suntory LimitedInventor: Charles J. Sih
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Patent number: 4931399Abstract: 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.Type: GrantFiled: September 9, 1985Date of Patent: June 5, 1990Assignee: The Wisconsin Alumni Research FoundationInventor: Charles J. Sih
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Patent number: 4861724Abstract: 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.Type: GrantFiled: November 3, 1987Date of Patent: August 29, 1989Assignee: Wisconsin Alumni Research FoundationInventor: Charles J. Sih
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Patent number: 4755463Abstract: 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.Type: GrantFiled: February 19, 1986Date of Patent: July 5, 1988Assignee: Wisconsin Alumni Research FoundationInventor: Charles J. Sih
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Patent number: 4710468Abstract: 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.Type: GrantFiled: February 15, 1984Date of Patent: December 1, 1987Assignee: Sigma-Tau Industrie Pharmaceutiche Riunite S.p.A.Inventor: Charles J. Sih
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Patent number: 4642290Abstract: 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.Type: GrantFiled: December 6, 1982Date of Patent: February 10, 1987Inventor: Charles J. Sih
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Patent number: 4584270Abstract: 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.Type: GrantFiled: January 23, 1984Date of Patent: April 22, 1986Assignee: Wisconsin Alumni Research FoundationInventor: Charles J. Sih
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Patent number: 4461835Abstract: 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.Type: GrantFiled: July 2, 1982Date of Patent: July 24, 1984Assignee: Wisconsin Alumni Research FoundationInventor: Charles J. Sih
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Patent number: 4444884Abstract: 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.Type: GrantFiled: September 21, 1982Date of Patent: April 24, 1984Assignee: Wisconsin Alumni Research FoundationInventor: Charles J. Sih
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Patent number: 4149017Abstract: Useful intermediates in the preparation of bicycloalkyl analogues or derivatives of prostaglandins are represented by the formula ##STR1## wherein: X is an iodo or bromo radical;A is an acid-labile hydroxyl-protecting group;G is an integer having a value of from 0 to 10; andB is selected for the class of bicycloalkyl radicals of the formula: ##STR2## WHERE M AND P ARE INTEGERS HAVING A VALUE OF FROM 1 TO 4; N IS AN INTEGER HAVING A VALUE OF FROM 0 TO 4 SUCH THAT THE SUM OF M, N AND P IS GREATER THAN OR EQUAL TO 3 AND THE POINT OF ATTACHMENT OF THE ALKYL CHAIN (CH.sub.2).sub.g to the bicycloalkyl radical is in the (CH.sub.2).sub.m bridge or in the bridgehead position.Type: GrantFiled: July 25, 1977Date of Patent: April 10, 1979Assignee: Miles Laboratories, Inc.Inventors: Warren D. Woessner, Charles J. Sih, Harold C. Kluender, Henry C. Arndt, William G. Biddlecom
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Patent number: 4142056Abstract: Racemic 15-deoxy, 11,15-deoxy and other prostaglandins and methods for preparing the same. The initial reactant is lithium cyclopentadiene which is reacted with ethyl-7-bromoheptanoate to give the alkylated diene which in turn is oxygenated to a mixture of hydroxycyclopentenones. 2-(6'-carboethoxyhexyl)-4-hydroxy-cyclopenten-1-one is chromatographically recovered from the mixture and reacted with dihydropyran to give the tetrahydropyranyl ether which is then reacted with 1-lithium-1-transoctene in the presence of tri-n-butylphosphine-copper iodide to produce racemic 15-deoxy-prostaglandin E.sub.1 ethyl ester which is chromatographically recovered. The ester is converted to the corresponding prostaglandin by the action of an esterase-producing microorganism.Type: GrantFiled: February 25, 1977Date of Patent: February 27, 1979Assignee: Wisconsin Alumni Research FoundationInventor: Charles J. Sih
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Patent number: 4138582Abstract: Analogues of prostaglandins A, E, and F in which the C.sub.13 -C.sub.20 chain of the natural prostaglandins is replaced by a cycloalkenyl or a hydroxycycloalkenyl moiety such that vinylene radical and the hydroxyl group of the ring respectively retain their natural sequential positions at C.sub.13 -C.sub.14 and C.sub.15, inhibit aggregation of platelets in vitro and exhibit useful cardiovascular activity in vivo.Type: GrantFiled: June 6, 1977Date of Patent: February 6, 1979Assignee: Miles Laboratories, Inc.Inventors: Warren D. Woessner, William G. Biddlecom, Henry C. Arndt, George P. Peruzzotti, Charles J. Sih
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Patent number: 4138583Abstract: Analogues of prostaglandins A, E, and F in which the C.sub.13 -C.sub.20 chain of the natural prostaglandins is replaced by a cycloalkenyl or a hydroxycycloalkenyl moiety such that vinylene radical and the hydroxyl group of the ring respectively retain their natural sequential positions at C.sub.13 -C.sub.14 and C.sub.15, inhibit aggregation of platelets in vitro and exhibit useful cardiovascular activity in vivo.Type: GrantFiled: June 6, 1977Date of Patent: February 6, 1979Assignee: Miles Laboratories, Inc.Inventors: Warren D. Woessner, William G. Biddlecom, Henry C. Arndt, George P. Peruzzotti, Charles J. Sih
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Patent number: RE29990Abstract: A method for stereospecifically preparing chiral 2-substituted-4-hydroxy-2-cyclopenten-1-one which comprises asymmetrically reducing 2-substituted cyclopentane-1,3,4-trione to the corresponding 2-substituted-4(R)-hydroxy-cyclopentane-1,3-dione, enolizing the said dione to obtain the enol ester or enol ether configuration, reducing the enol ester or ether and recovering the desired compound. The chiral 2-substituted-4-hydroxy-2-cyclopenten-1-one are key intermediates in the preparation of prostaglandins.Type: GrantFiled: November 4, 1977Date of Patent: May 8, 1979Assignee: Wisconsin Alumni Research FoundationInventors: Charles J. Sih, James B. Heather