Department of Chemistry and Biochemistry, University of North Carolina at Greensboro , Greensboro, North Carolina 27402, United States.
J Nat Prod. 2012 Nov 26;75(11):1879-81. doi: 10.1021/np3005369. Epub 2012 Nov 1.
Isosilybin A (1) is one of the major flavonolignans that constitute silymarin, an extract of the fruits (achenes) of milk thistle (Silybum marianum). The chemistry of the Silybum flavonolignans has been studied for over four decades, and the absolute configuration of 1 has been determined previously by electronic circular dichroism and X-ray crystallography via correlating the relative configuration of the phenylpropanoid moiety to the established absolute configuration of the 3-hydroxyflavanone portion of the molecule. Herein we report the X-ray crystallographic structure of the product of the reaction of 1 with 4-bromobenzoyl chloride, and, thus, the absolute configuration of 1 was established as (2R, 3R, 7″R, 8″R) directly via X-ray crystallography of an analogue that incorporated a heavy atom. The results were consistent with previously reported assignments and verified the absolute configuration of the diastereoisomer of 1, isosilybin B, and the related diastereoisomeric regioisomers, silybin A and silybin B.
水飞蓟宾 A（1）是构成水飞蓟素的主要黄酮木脂素之一，水飞蓟素是奶蓟（水飞蓟）果实（瘦果）的提取物。四十多年来一直在研究水飞蓟黄酮木脂素的化学，通过将苯丙素部分的相对构型与分子中 3-羟基黄酮部分的已建立的绝对构型相关联，以前曾通过电子圆二色性和 X 射线晶体学确定 1 的绝对构型。在此，我们报告了 1 与 4-溴苯甲酰氯反应产物的 X 射线晶体结构，因此，通过引入重原子的类似物的 X 射线晶体学直接确定了 1 的绝对构型为（2R，3R，7″R，8″R）。结果与先前报道的分配结果一致，并验证了 1 的非对映异构体，水飞蓟宾 B 以及相关的非对映异构体区域异构体，水飞蓟宾 A 和水飞蓟宾 B 的绝对构型。
