Applied Chemistry for Engineering (공업화학)

The Korean Society of Industrial and Engineering Chemistry (한국공업화학회)
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Efficient Stereoselective Synthesis of (2S,3S,4S)-3,4-Dihydroxyglutamic Acid

(2S,3S,4S)-3,4-다이하이드록시글루타믹산의 효율적인 입체선택적 합성

  • Jeon, Jongho (Department of Chemical and Biological Engineering, Seoul National University) ;
  • Shin, Nara (Department of Chemical and Biological Engineering, Seoul National University) ;
  • Lee, Jong Hyup (Department of Chemical and Biological Engineering, Seoul National University) ;
  • Kim, Young Gyu (Department of Chemical and Biological Engineering, Seoul National University)
  • 전종호 (서울대학교 공과대학 화학생물공학부) ;
  • 신나라 (서울대학교 공과대학 화학생물공학부) ;
  • 이종협 (서울대학교 공과대학 화학생물공학부) ;
  • 김영규 (서울대학교 공과대학 화학생물공학부)
  • Received : 2014.04.29
  • Accepted : 2014.07.14
  • Published : 2014.08.10
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Abstract

(2S,3S,4S)-3,4-Dihydroxyglutamic acid (DHGA), a biologically active ${\alpha},{\beta}$-dihydroxy-${\gamma}$-amino acid, was efficiently synthesized from a readily available D-serine derivative in 30% overall yield over 11 steps. The key stereoselective $OsO_4$-catalyzed dihydroxylation reaction controlled by an N-diphenylmethylene group on the amino group of ${\gamma}$-amino-${\alpha},{\beta}$-unsaturated (Z)-ester successfully introduced the diol moiety of the intermediate 5a in 86% with more than 10 : 1 diastereomeric ration. Then it was in turn successfully converted to the desired target compound, (2S,3S,4S)-3,4-DHGA, via simple oxidation and hydrolysis in a highly stereoselective manner and a higher yield than the previous syntheses. This result strongly supports that our synthetic methodology of stereoselective $OsO_4$-catalyzed dihydroxylation should be useful in stereoselctive synthesis of various bioactive compounds with an amino diol moiety.

생리학적 활성을 가진 (2S,3S,4S)-3,4-다이하이드록시 글루타믹산(DHGA)을 값이 저렴하고 수급이 용이한 D-serine 유도체로부터 효율적으로 합성하였다. D-serine 유도체로부터 얻어진 ${\gamma}$-아미노-${\alpha},{\beta}$-불포화성(Z)-에스터의 아민에 다이페닐메틸렌기를 도입, 이를 이용한 입체선택적 이 중 알코올화 반응을 통해 2,3 위치에 두 개의 하이드록시기를 10 : 1 이상의 높은 선택성과 86%의 높은 수율로 도입하여 중간체 5a를 효율적으로 합성하였고, 이 중간체의 간단한 산화 및 가수분해 반응을 통해 (2S,3S,4S)-3,4-DHGA 합성에 성공하였다. 이는 11단계에 총 30%의 수율과 입체선택적인 결과로 현재까지 보고된 (2S,3S,4S)-3,4-DHGA의 합성법 중에 가장 효율적이다. 이 결과는 $OsO_4$을 이용한 입체선택적 이중 알콜화 반응이 아미노 다이올을 포함하는 다양한 생리활성 물질의 효율적인 합성에 적용할 수 있음을 뒷받침한다.

Keywords

References

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