Chapter 3. Hetero Diels-Alder-Biocatalysis Approach for the Synthesis of (S)-3-[2-{(Methylsulfonyl)oxy}ethoxy]-4-(triphenylmethoxy)-1-butanol Methanesulfonate: Successful Application of an Enzyme Resolution Process

  1. Dr. Hans-Ulrich Blaser2,
  2. Dr. Elke Schmidt3
  1. Jean-Claude Caille,
  2. Jim Lalonde,
  3. Yiming Yao,
  4. C. K. Govindan

Published Online: 13 JAN 2004

DOI: 10.1002/3527602151.ch20

Book Title

Asymmetric Catalysis on Industrial Scale: Challenges, Approaches and Solutions

Asymmetric Catalysis on Industrial Scale: Challenges, Approaches and Solutions

Additional Information

How to Cite

Caille, J.-C., Lalonde, J., Yao, Y. and Govindan, C. K. (2004) Hetero Diels-Alder-Biocatalysis Approach for the Synthesis of (S)-3-[2-{(Methylsulfonyl)oxy}ethoxy]-4-(triphenylmethoxy)-1-butanol Methanesulfonate: Successful Application of an Enzyme Resolution Process, in Asymmetric Catalysis on Industrial Scale: Challenges, Approaches and Solutions (eds H.-U. Blaser and E. Schmidt), Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim, FRG. doi: 10.1002/3527602151.ch20

Editor Information

  1. 2

    Solvias AG, P.O. Box, CH-4002 Basel, Switzerland

  2. 3

    Syngenta Crop Protection AG, CH-4058 Basel, Switzerland

Author Information

  1. PPG-Sipsy, Sipsy Chimie Fine, Z.I. la Croix Cadeau B.P. 79, F-49242 Avrillé Cedex, France

Publication History

  1. Published Online: 13 JAN 2004
  2. Published Print: 6 NOV 2003

ISBN Information

Print ISBN: 9783527306312

Online ISBN: 9783527602155

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Keywords:

  • hetero Diels-Alder-biocatalysis;
  • synthesis;
  • (S)-3-[2-{(methylsulfonyl)oxy}ethoxy]-4-(triphenylmethoxy)-1-butanol methanesulfonate;
  • enzyme resolution;
  • (R,S)-4,3,6-dihydro-2H-pyran-2-ylmethanol;
  • butyl ester;
  • gas chromatography;
  • tritylation;
  • ozonolysis

Summary

This chapter contains sections titled:

  • Introduction

  • The Hetero Diels-Alder-Biocatalysis Strategy

  • Hetero Diels-Alder Reaction: Synthesis of 2-Ethoxycarbonyl-3,6-dihydro-2H-pyran, (R,S)-4

  • Enzymatic Resolution of (R,S)-4

    • Secondary Screen and E Determination

    • Protease Screen

    • Optimization of the Resolution of (R,S)-4

      • Buffer pH and Concentration

      • Optimization of Enzyme Loading and Other Parameters

  • Pilot Plant Trials

  • Attempted Resolution of 3,6-Dihydro-2H-pyran-2-ylmethanol, (R,S)-5

  • Experimental

    • Hydrolase Library Screening – Hydrolysis of (R,S)-4

    • Gram Scale Runs

    • Butyl Ester

    • Determination of Enantiomeric Purity by Gas Chromatography

    • Resolution of (R,S)-4

    • Reduction of (S)-4

    • Tritylation of 5

    • Reductive Ozonolysis of (S)-2-Trityloxymethyl-3,6-dihydro-2H-pyran, 6

    • Preparation of 1

  • Summary

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