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).

  • Patent number: 6316645
    Abstract: 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: Grant
    Filed: October 20, 1998
    Date of Patent: November 13, 2001
    Assignee: Wisconsin Alumni Research Foundation
    Inventors: Charles J. Sih, Chien-An Chen
  • Patent number: 5637500
    Abstract: 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: Grant
    Filed: September 26, 1994
    Date of Patent: June 10, 1997
    Assignee: Suntory Limited
    Inventor: Charles J. Sih
  • Patent number: 5608047
    Abstract: 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: Grant
    Filed: March 15, 1995
    Date of Patent: March 4, 1997
    Assignee: Wisconsin Alumni Research Foundation
    Inventor: Charles J. Sih
  • Patent number: 5541080
    Abstract: 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: Grant
    Filed: May 28, 1993
    Date of Patent: July 30, 1996
    Assignee: Wisconsin Alumni Research Fdn.
    Inventor: Charles J. Sih
  • Patent number: 5300430
    Abstract: 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: Grant
    Filed: January 7, 1993
    Date of Patent: April 5, 1994
    Assignee: Sigma-Tau Industrie Farmaceutiche Riunite S.p.A.
    Inventors: Stuart Shapiro, Manrico Bernardini, Charles J. Sih
  • Patent number: 5219731
    Abstract: 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: Grant
    Filed: November 1, 1991
    Date of Patent: June 15, 1993
    Assignee: Wisconsin Alumni Research Foundation
    Inventor: Charles J. Sih
  • Patent number: 5128264
    Abstract: 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: Grant
    Filed: August 13, 1990
    Date of Patent: July 7, 1992
    Assignee: Suntory Limited
    Inventor: Charles J. Sih
  • Patent number: 4931399
    Abstract: 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: Grant
    Filed: September 9, 1985
    Date of Patent: June 5, 1990
    Assignee: The Wisconsin Alumni Research Foundation
    Inventor: Charles J. Sih
  • Patent number: 4861724
    Abstract: 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: Grant
    Filed: November 3, 1987
    Date of Patent: August 29, 1989
    Assignee: Wisconsin Alumni Research Foundation
    Inventor: Charles J. Sih
  • Patent number: 4755463
    Abstract: 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: Grant
    Filed: February 19, 1986
    Date of Patent: July 5, 1988
    Assignee: Wisconsin Alumni Research Foundation
    Inventor: Charles J. Sih
  • Patent number: 4710468
    Abstract: 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: Grant
    Filed: February 15, 1984
    Date of Patent: December 1, 1987
    Assignee: Sigma-Tau Industrie Pharmaceutiche Riunite S.p.A.
    Inventor: Charles J. Sih
  • Patent number: 4642290
    Abstract: 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: Grant
    Filed: December 6, 1982
    Date of Patent: February 10, 1987
    Inventor: Charles J. Sih
  • Patent number: 4584270
    Abstract: 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: Grant
    Filed: January 23, 1984
    Date of Patent: April 22, 1986
    Assignee: Wisconsin Alumni Research Foundation
    Inventor: Charles J. Sih
  • Patent number: 4461835
    Abstract: 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: Grant
    Filed: July 2, 1982
    Date of Patent: July 24, 1984
    Assignee: Wisconsin Alumni Research Foundation
    Inventor: Charles J. Sih
  • Patent number: 4444884
    Abstract: 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: Grant
    Filed: September 21, 1982
    Date of Patent: April 24, 1984
    Assignee: Wisconsin Alumni Research Foundation
    Inventor: Charles J. Sih
  • Patent number: 4149017
    Abstract: 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: Grant
    Filed: July 25, 1977
    Date of Patent: April 10, 1979
    Assignee: Miles Laboratories, Inc.
    Inventors: Warren D. Woessner, Charles J. Sih, Harold C. Kluender, Henry C. Arndt, William G. Biddlecom
  • Patent number: 4142056
    Abstract: 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: Grant
    Filed: February 25, 1977
    Date of Patent: February 27, 1979
    Assignee: Wisconsin Alumni Research Foundation
    Inventor: Charles J. Sih
  • Patent number: 4138583
    Abstract: 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: Grant
    Filed: June 6, 1977
    Date of Patent: February 6, 1979
    Assignee: Miles Laboratories, Inc.
    Inventors: Warren D. Woessner, William G. Biddlecom, Henry C. Arndt, George P. Peruzzotti, Charles J. Sih
  • Patent number: 4138582
    Abstract: 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: Grant
    Filed: June 6, 1977
    Date of Patent: February 6, 1979
    Assignee: Miles Laboratories, Inc.
    Inventors: Warren D. Woessner, William G. Biddlecom, Henry C. Arndt, George P. Peruzzotti, Charles J. Sih
  • Patent number: RE29990
    Abstract: 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: Grant
    Filed: November 4, 1977
    Date of Patent: May 8, 1979
    Assignee: Wisconsin Alumni Research Foundation
    Inventors: Charles J. Sih, James B. Heather