Bulletin of the Korean Chemical Society

Korean Chemical Society (대한화학회)
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From L-Ascorbic Acid to Protease Inhibitors: Practical Synthesis of Key Chiral Epoxide Intermediates for Aspartyl Proteases

  • Chang, Sun-Ki (Research Institute for Basic Sciences and Department of Chemistry, College of Sciences, Kyung Hee University) ;
  • So, Soon-Mog (Department of Chemistry, Seoul National University, College of Natural Sciences) ;
  • Lee, Sang-Min (Department of Chemistry, Seoul National University, College of Natural Sciences) ;
  • Kim, Min-Kyu (ST Pharm Co., Ltd. Shihwa Industrial Complex) ;
  • Seol, Kyoung-Mee (ST Pharm Co., Ltd. Shihwa Industrial Complex) ;
  • Kim, Sung-Min (ST Pharm Co., Ltd. Shihwa Industrial Complex) ;
  • Kang, Jae-Sung (ST Pharm Co., Ltd. Shihwa Industrial Complex) ;
  • Choo, Dong-Joon (Research Institute for Basic Sciences and Department of Chemistry, College of Sciences, Kyung Hee University) ;
  • Lee, Jae-Yeol (Research Institute for Basic Sciences and Department of Chemistry, College of Sciences, Kyung Hee University) ;
  • Kim, B.-Moon (Department of Chemistry, Seoul National University, College of Natural Sciences)
  • Received : 2011.12.08
  • Accepted : 2012.03.30
  • Published : 2012.07.20
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Abstract

Efficient synthetic routes were developed to prepare a sizable amount (4-15 grams) of the chiral epoxides 4-6 as versatile intermediates for the synthesis of aspartyl protease inhibitors of therapeutic interest such as HIV protease and ${\beta}$-secretase. Oxidative cleavage of the C(2)-C(3) double bond of L-ascorbic acid followed by functional group manipulation led to the preparation of the epoxide 10, which was opened with an azide to yield a common aziridine intermediate 12. Through opening of the aziridine ring of 12 with either a carbon or a sulfur nucleophile, chiral epoxide precursors 4-6 could be prepared for various HIV protease inhibitors. Except for the final low melting epoxides 5 and 6, all intermediates were obtained as crystalline solids, thus the synthetic pathway can be easily applied to a large-scale synthesis of the chiral epoxides.

Keywords

References

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