The first enantiocontrolled total synthesis of the marine sponge metabolite chlorodysinosin A is described. The structure and absolute configuration are identical to those of dysinosin A except for the presence of a novel 2S,3R-3-chloroleucine residue in the former. A concise stereocontrolled synthesis of the new chlorine-containing amino acid fragment was developed. An X-ray cocrystal structure of synthetic chlorodysinosin A with the enzyme thrombin confirms the structure and configuration assignment achieved through total synthesis. Within the aeruginosin family of natural products, chlorodysinosin A is the most potent inhibitor of the serine proteases thrombin, factor VIIa, and factor Xa, which are critical enzymes in the process leading to platelet aggregation and fibrin mesh formation in humans.

中文翻译：

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Chlorodysinosin A 的全合成和结构确认

描述了海洋海绵代谢物氯化肌球蛋白 A 的第一个对映体控制的全合成。除了在前者中存在新的 2S,3R-3-氯亮氨酸残基外，其结构和绝对构型与肌胞苷 A 相同。开发了新的含氯氨基酸片段的简洁立体控制合成。合成氯肌球蛋白 A 与凝血酶的 X 射线共晶结构证实了通过全合成实现的结构和构型分配。在天然产物铜绿素家族中，氯肌球蛋白 A 是丝氨酸蛋白酶凝血酶、凝血酶因子 VIIa 和因子 Xa 的最有效抑制剂，这些酶是导致人类血小板聚集和纤维蛋白网形成过程中的关键酶。