Elsevier

Tetrahedron: Asymmetry

Volume 16, Issue 16, 22 August 2005, Pages 2717-2721
Tetrahedron: Asymmetry

A simple and practical approach to enantiomerically pure (S)-3-hydroxy-γ-butyrolactone: synthesis of (R)-4-cyano-3-hydroxybutyric acid ethyl ester

https://doi.org/10.1016/j.tetasy.2005.07.012Get rights and content

Abstract

The oxidation of α- or β-(1,4) linked disaccharides or oligosaccharides with cumene hydroperoxide in the presence of a base gave (S)-3,4-dihydroxybutyric acid, which was cyclized under acidic conditions to furnish (S)-3-hydroxy-γ-butyrolactone. This was subsequently converted into (R)-cyano-3-hydroxybutyric acid ethyl ester, an intermediate for statin based drugs and other related compounds.

Introduction

(S)-3-Hydroxy-γ-butyrolactone is an important synthetic intermediate for a variety of chiral compounds. It serves as key intermediate for the preparation of neuromediator (R)-GABOB, l-carnitine,1 and HMG-CoA reductase inhibitor, CI-981.2 (S)-3-Tetrahydrofuran derived from 3-hydroxy-γ-butyrolactone is an intermediate for an AIDS drug.3 (S)-3-Hydroxy-γ-butyrolactone has been reported as a satiety agent as well as a potentiating agent to neuroleptic drugs.4 Its utility as a synthetic intermediate for a variety of natural products is well documented.5

The synthesis of (S)-3-hydroxy-γ-butyrolactone has been accomplished by employing various synthetic strategies. A commonly used strategy for its synthesis and for its intermediate (S)-3-hydroxybutyric acid derivatives is from the enzymatic or catalytic β-keto ester reduction.6 It has also been prepared from the selective reduction of l-malic acid ester.7 There have been reports of its synthesis from carbohydrate sources as well, either using just a base or a combination of a base and an oxidant. The treatment of a carbohydrate containing glucose substituent in the 4-position, such as cellobiose, amylose, and cellulose with alkali, has been shown to produce a low yield of the desired material along with d,l-2,4-dihydroxybutyric acid, glycolic acid, isosaccharinic acid, ketones, diketones, glycolic acid, and a plethora of other degradation and condensation products.8 Similarly, the alkaline oxidation of a carbohydrate containing a glucose substituent at the 4-position is known to give a dicarbonyl compound, which is then oxidized to furnish (S)-3,4-dihydroxybutyric acid.9 The yield reported for the desired compound is very low due to the formation of a large number of by-products.

Defunctionalization of a carbohydrate has been attracting much attention as a useful synthetic tool for the enantioselective synthesis of a variety of compounds. The synthesis of a chiral compound with a desired number of stereogenic centers could be achieved by eliminating the unneeded stereogenic centers quickly from the carbohydrate precursors. Though a large number of small scale complex syntheses of (S)-3-hydroxy-γ-butyrolactone have been developed, the majority of these methods suffer from drawbacks such as multi-step synthesis, long reaction times, high temperature, enzymatic methods, and use of expensive metal catalysts for the reduction of the prochiral center, side reactions, low enantiomeric purity, and overall low yield of product. Therefore, there is genuine need for a simple and inexpensive method for the large-scale preparation of (S)-3-hydroxy-γ-butyrolactone and its derivatives.10 We, herein, report the synthesis of the title compound by employing the oxidation of a 1,4-linked d-hexose sugar under basic conditions.

Section snippets

Results and discussion

The synthesis of (S)-3-hydroxy-γ-butyrolactone started from the readily available carbohydrate source as depicted in Scheme 1. Thus, a 1,4-linked d-hexose sugar, such as maltose/maltodextrin/lactose, was treated with cumene hydroperoxide under basic conditions at 70 °C to give 3,4-dihydroxybutyric acid 2, which was cyclized in the presence of an acid to afford the desired butyrolactone 4 in reasonably good yield.

The advantages of the present method are that it is simple, practical, and

Conclusion

In conclusion, a method for preparing enantiomerically pure (S)-3-hydroxy-γ-butyrolactone by the oxidation of a (1,4)-linked disaccharide or oligosaccharide with cumene hydroperoxide has been developed. The process uses an inexpensive and readily available carbohydrate as the chiral pool material. The hydroxy butyrolactone has further been converted into (R)-cyano-3-hydroxybutyric acid ethyl ester, which is a useful intermediate for the statin based drugs and other related compounds.

General information

The solvents were purified and dried by the standard procedures prior to use; petroleum ether of boiling range 60–80 °C was used. Optical rotation was measured using sodium D line on a JASCO-P-1020-polarimeter. Infrared spectra were recorded on a Perkin Elmer FT-IR spectrometer. 1H NMR spectra were recorded on a Bruker AC-200 spectrometer. The mass spectra were recorded either by GC–MS or with a Finnigan LC–MS mass spectrometer. Enantiomeric excess was measured using either chiral HPLC or by

Acknowledgements

Financial support to this work under NMITLI programme (Grant No. 5/258/2/2000-NMITLI) is gratefully acknowledged. This is NCL Communication No. 6684.

References (13)

  • M. Larchevêque et al.

    Tetrahedron

    (1990)
  • P.L. Brower et al.

    Tetrahedron Lett.

    (1992)
  • J.W. Green

    J. Am. Chem. Soc.

    (1956)
    R.M. Rowell et al.

    Carbohydr. Res.

    (1969)
  • Gurjar, M. K.; Kumar, P.; Deshmukh, A. N.; Upadhyay, R. K.; Upadhyay, P. K. USP...
  • E.E. Kim et al.

    J. Am. Chem. Soc.

    (1995)
  • O. Uchikawa et al.

    Bull. Chem. Soc. Jpn.

    (1988)
    (b)Fuxe , K. USP...
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