Journal of Life Science (생명과학회지)

Korean Society of Life Science (한국생명과학회)
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Synthesis of N-acyl-α-aminosuccinimides and N-acyl-α-aminoglutarimides

N-아실-α-아미노숙신이미드와 N-아실-α-아미노글루탈이미드의 합성

  • Published : 2004.02.01
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Abstract

As a part of our study on the improvement of anticonvulsant, here we report the synthesis of N-acyl-$\alpha$-aminosuc-cinimides 1 and N-acyl-$\alpha$-aminoglutarimides 2. (R)-Benzoic acid 4-benzyloxycarbonylamino-2-oxo-pyrrolidin-1-ylester 6a, (R)-4-nifro-benzoic acid 4-benzyloxycarbonylamino-2- oxo-pyrrolidin-1-yl ester 6b, (R) -4-nitro-benzoic acid 4-benzyloxycarbonylamino-2-oxo-pyrrolidin-1-yl ester 6c, and (R)-propionic acid 4-benzyloxycarbonylamino-2-oxo-pyrrolidin-1-yl ester 6d were synthesized from (R)-2-benzyloxy carbonylamino-succinic acid 3 as a starting meterial. (R)-(3- Benzyloxycarbonylamino-2,6-dioxo-piperidin-1-yloxy)-acetic acid methyl ester 10a, (R)-(3-benzyloxycarbonylamino-2,6-dioxo-piperidin-1-yloxy)-acetic acid ethy1 ester 10b, an d (R)-2-(3-benzyloxycarbonylamino-2,6- diox o-piperidin-1-yl oxy)-propionic acid methyl ester l0c were synthesized from (R)- 3-carbobenzyloxy-amino-glutarmic acid 7 as a starting meterial. The yield, mp, IR, $^1H-NMR,\; and^{13}C$- NMR spectra of the products 6a, 6b, 6c, 6d, 10a, l0b, l0c are summarized in footnote. The biological studies of these compounds are in progress and will be reported in future.

앞선 연구의 구조적 특성을 근거로 하여, 한 분자내에 MES 유발경련에 작용하는 cyclicimide의 구조를 포함하면, 그들의 구조가 경련 유발 수용체들에 상호 보완적으로 작용, MES및 PTZ유발 경련에 모두 작용할 수 있는 적용 범위가 넓은 항경련성 화합물이 될 수 있을 것으로 생각하여 N-acyl-$\alpha$-aminosuccinimide 1과 N-acyl-$\alpha$-aminoglutar- imide 2 유도체를 합성하였다. 먼저 (R)-2-benzyloxy carbonylamino-succinic acid 3을 출발 물질로 하여 N-acyl-a-aminosuccinimide 1 유도체인 (R)-Benzoic acid 4-benzyloxycarbonyl-amino-2-oxo-pyrrolidin-l-yl ester 6a, (R)4-nitro-benzoic acid 4-benzyloxycarbon-ylamino-2-oxo-pyrrolidin-1-yl ester 6b, (R)-4-nitro-benzoic acid 4-benzyloxycarbonylamino-2-oxo-pyrrolidin-1-yl ester 6c, 그리고 (R)-propionic acid 4-benzyloxycarbonylamino-2-oxo-pyrrolidin-1-yl ester 64를 합성하였다 또한 (R)-3-car-bobenzyloxy-aminoglutarrnic acid 7를 출발물질로 하여 N-acyl-$\alpha$-aminoglutarimide 2유도체인 (R)-(3-Benzyloxycarbonyl-amino-2,6-dioxo-piperidin-1-yloxy)-acetic acid methyl ester 10a, (R)-(3-benzyloxyarbonylamino-2,6-dioxo-piperidin-1-yloxy)-acetic acid ethyl ester l0b, 그리고 (R)-2-(3-benzylox-ycarbonylanino-2,6-dioxo-piperidin-1-yloxy)-propionic acid methyl ester l0c를 합성하였다. 합성된 화합물 6a, 6b, 6c, 6d, 10a, lOb, l0c에 대한 활성평가는 각 단계별 MES test와 PTZ test의 항경련 활성 시험 방법을 가지고 실험할 예정이다.

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