立体化学阐明和二白胺酸D的总合成,这是一个半合成的白胺酸
C G Boojamra1, R C Lemoine, J C Lee
1Microcide Pharmaceuticals, Inc., 850 Maude Avenue, Mountain View, California 94043, USA.
半合成的二白胺氨酸保留了抗菌活性. 通过降解和总合成,对帕奇达米辛D及其衍生物进行了详细的立体化学分析.
科学领域:
- 自然产品化学 自然产品化学
- 药用化学 医学化学
- 有机合成 有机合成
背景情况:
- 帕西达米辛是具有抗菌性能的天然产品.
- 半合成修改可以产生具有类似或增强活性的化合物.
- 立体化学对于生物活动至关重要.
研究的目的:
- 通过化帕奇达米辛,合成二帕奇达米辛.
- 为了阐明帕奇达米辛D的完整立体化学.
- 为了确认氨基酸残留和核酸位点的立体化学配置.
主要方法:
- 帕奇达米辛的C(4') 外环烯的化.
- 自然产品降解的实验.
- 总合成的二白胺素 D.
主要成果:
- 半合成二白胺氨酸表现出与天然白胺氨酸相当的抗菌活性.
- 帕奇达米辛D中托和氨酸残留物的立体化学相同性被证实为 (S).
- 在化后,3-甲基氨基-2-氨基黄油酸残留物被确定为 (2S,3S),而C(4') 核酸位是 (R).
结论:
- 帕奇达米辛的化产生了活性半合成类型.
- 帕奇达米辛D及其成分的立体化学已经完全阐明.
- 已建立的立体化学配置为理解结构-活动关系提供了基础.
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