Process for producing optically active 2-alkyl-1,1,3-trialkoxycarbonylpropane

a technology of trialkoxycarbonylpropane and alkyl sulfonate, which is applied in the direction of hydrolases, sulfuration, bulk chemical production, etc., can solve the problem that the method is not necessarily satisfactory

Inactive Publication Date: 2015-08-06
GENENTECH INC
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The inventors have discovered a way to easily produce optically active 2-alkyl-1,1,3-trialkoxycarbonylpropane by using enzymes to hydrolyze a racemic form of the material. This process allows for the easy and efficient production of both isomers.

Problems solved by technology

Additionally, even when the reaction is conducted at −78° C., the optical purity is at most 93% ee (43% ee when the alkyl group that binds to the carbon atom serving as optically-active center is a methyl group), so that this method is not necessarily satisfactory from the industrial view.

Method used

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  • Process for producing optically active 2-alkyl-1,1,3-trialkoxycarbonylpropane
  • Process for producing optically active 2-alkyl-1,1,3-trialkoxycarbonylpropane
  • Process for producing optically active 2-alkyl-1,1,3-trialkoxycarbonylpropane

Examples

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examples

[0056]In the following, the present invention will be explained more specifically by way of examples; however, the present invention is not limited to these examples.

examples 1 to 14

[0057]To 35 mg of 2-methyl-1,1,3-trimethoxycarbonylpropane and each of various enzymes shown in Table 1 respectively weighed in the amount shown in Table 2, 2 mL of 100 mM potassium phosphate buffer (pH 7.0) was added. The resultant solution was stirred at 25° C. for 20 hours, and then 2.5 mL of acetonitrile was added thereto and the mixture was drawn through a membrane filter. The optical purity of the resultant filtrate was analyzed by high performance liquid chromatography [column: CHIRALCEL (registered trademark) OB-H, 4.6 mmφ×15 cm, 5 μm (produced by Daicel Chemical Industries, Ltd.)], and the chemical purity was analyzed by high performance liquid chromatography [column: SUMIPAX ODS D-210FF, 4.6 mmφ×15 cm, 3 μm (available from Sumika Chemical Analysis Service, Ltd.)]; and thus, yield and enantiomer excess of the obtained optically active 2-methyl-1,1,3-trimethoxycarbonylpropane were determined. The results are shown in Table 2.

examples 15 , 16

Examples 15, 16

[0058]To 70 mg of 2-methyl-1,1,3-trimethoxycarbonylpropane and an enzyme shown in Table 1 weighed in the amount shown in Table 2, 4 mL of 100 mM potassium phosphate buffer (pH 7.0) was added. The resultant solution was stirred at 25° C. for 3.5 hours, and then 5 mL of acetonitrile was added thereto and the mixture was drawn through a membrane filter. The filtrate was analyzed in the same method as in Examples 1 to 14, and yield and enantiomer excess of obtained optically active 2-methyl-1,1,3-trimethoxycarbonylpropane were determined. The results are shown in Table 2.

TABLE 1EnzymemanufacturerPreparation(commerciallymethod ofExampleName of enzymeOrigin of enzymeavailable enzyme)enzyme1CholesterolCandidaRoche DiagnosticsEsterasecylindracea2CHIRAZYME E-3, lyoThermophilicRoche Diagnosticsmicro-organism3Cholesterol esterase, lyoCandidaRoche Diagnostics4PLE-APig liverAmano Enzyme5ChiroCLEC-CRCandida rugosaAltus Biologics6CHIRAZYME L-3Candida rugosaRoche Diagnostics7Lipase O...

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Abstract

A process for producing an optically active 2-alkyl-1,1,3-trialkoxycarbonylpropane (2), comprising a step of asymmetric hydrolysis of 2-alkyl-1,1,3-trialokoxycarbonylpropane (1) by using an enzyme capable of selectively hydrolyzing an ester moiety of either one enantiomer of 2-alkyl-1,1,3-trialkoxycarbonylpropane (1), or by using a culture of a microorganism capable of producing the enzyme or a treated object thereof.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application is a continuation of U.S. patent application Ser. No. 12 / 599,338, filed Nov. 9, 2009, now allowed, which is a 371 of International Patent Application No. PCT / JP2008 / 058991, filed May 9, 2008, which was published on Nov. 20, 2008 under International Publication No. WO 2008 / 140127 A1. The entire content of the applications referenced above are hereby incorporated by reference herein. This application also claims priority to Japanese Patent Application No. 2007-127704, filed May 14, 2007, Japanese Patent Application No. 2007-141542, filed May 29, 2007, and Japanese Patent Application No. 2008-083302, filed Mar. 27, 2008.TECHNICAL FIELD[0002]The present invention relates to a process for producing an optically active 2-alkyl-1,1,3-trialkoxycarbonylpropane.BACKGROUND ART[0003]An optically active 2-alkyl-1,1,3-trialkoxycarbonylpropane is a compound useful as a material for formation of an asymmetric carbon atom in synthesis of ...

Claims

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Application Information

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Patent Type & AuthorityApplications(United States)
IPC IPC(8): C12P7/62
CPCC12P41/005C12P7/62C12N9/18Y02P20/52
InventorHIRATA, NORIHIKOYAMAUCHI, KAZUHIRO
OwnerGENENTECH INC