（±）-环磷酰胺和（±）-环磷酰胺 P 的全合成：丝氨酸水解酶乙酰胆碱酯酶和激素敏感脂肪酶的抑制剂。
The first total synthesis of (±)-cyclophostin and (±)-cyclipostin P: inhibitors of the serine hydrolases acetyl cholinesterase and hormone sensitive lipase.
机构信息
Department of Chemistry and Biochemistry, University of Missouri-St. Louis, One University Boulevard, St. Louis, Missouri 63121, USA.
出版信息
Org Lett. 2011 Jun 17;13(12):3094-7. doi: 10.1021/ol200991x. Epub 2011 May 17.
Abstract
Cyclophostin, a structurally unique and potent naturally occurring acetyl cholinesterase (AChE) inhibitor, and its unnatural diastereomer were prepared in 6 steps and 15% overall yield from hydroxymethyl butyrolactone. The unnatural diastereomer of cyclophostin was converted into cyclipostin P, a potent naturally occurring hormone sensitive lipase (HSL) inhibitor, using a one pot dealkylation-alkylation process. The inhibition [IC(50)] of human AChE by cyclophostin and its diastereomer are reported, as well as constituent binding (K(I)) and reactivity (k(2)) constants.
摘要
环磷酰胺是一种结构独特且强效的天然乙酰胆碱酯酶 (AChE) 抑制剂，其非天然对映异构体可由羟甲基丁内酯经 6 步反应、总收率 15%制备得到。利用一锅脱烷基-烷基化过程，可将环磷酰胺的非天然对映异构体转化为强效的天然激素敏感脂肪酶 (HSL) 抑制剂环磷酰胺 P。本文报道了环磷酰胺及其非天然对映异构体对人乙酰胆碱酯酶的抑制作用 [IC(50)]，以及结合常数 (K(I)) 和反应常数 (k(2))。
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2
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