新的 C-2 差向异构体黄酮糖苷与 3-羟基-3-甲基戊二酸从柑橘果皮（L.）Osbeck。

New C-2 diastereomers of flavanone glycosides conjugated with 3-hydroxy-3-methylglutaric acid from the pericarp of Citrus grandis (L.) Osbeck.

机构信息

State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.

出版信息

Bioorg Chem. 2018 Oct;80:519-524. doi: 10.1016/j.bioorg.2018.06.024. Epub 2018 Jun 27.

DOI:10.1016/j.bioorg.2018.06.024

PMID:30005202

Abstract

Two new 3-hydroxy-3-methylglutaryl (HMG) flavanone 7-O-diglycosides, cigranosides A and B (1 and 2), the known naringenin 7-(2''-α-rhamnosyl-6''-(3''''-hydroxy-3''''-methylglutaryl)-glucoside (melitidin, 3), their common biosynthetic precursor flavanone 7-O-diglycoside (naringin, 4), and one known flavone 7-O-diglycoside (rhoifolin, 5) were isolated from the pericarp of Citrus grandis (L.) Osbeck. The structures of these compounds were elucidated by spectroscopic and chemical techniques. The relative ratios and absolute configurations of the C-2 diastereomers of compounds 1, 2 and 4 were determined by online normal-phase HPLC-CD using a Chiralcel column. The absolute configuration of the HMG fragment in compounds 1-3 was assigned to be S through spectroscopic analysis of the mevalonamide obtained by amidation and reduction of the HMG moiety. The NO inhibitory activities of compounds 1-5 were evaluated using lipopolysaccharide-induced RAW264.7 cells. Compounds 1-5 were not cytotoxic to RAW264.7 cells at 10 μM.

摘要

从柚子（Citrus grandis （L.）Osbeck）的果皮中分离得到两种新的 3-羟基-3-甲基戊二酰基（HMG）二氢黄酮醇 7-O-二糖苷，即 cigranoside A 和 B（1 和 2），已知的柚皮素 7-（2”-α-鼠李糖基-6”-（3''''-羟基-3''''-甲基戊二酰基）-葡萄糖苷（melitidin，3），它们共同的生物合成前体二氢黄酮醇 7-O-二糖苷（柚皮苷，4），以及一种已知的黄酮醇 7-O-二糖苷（rhoifolin，5）。这些化合物的结构通过光谱和化学技术阐明。通过使用手性柱在正相 HPLC-CD 上在线测定化合物 1、2 和 4 的 C-2 非对映异构体的相对比例和绝对构型。通过对 HMG 部分进行酰胺化和还原得到的 mevalonamide 的光谱分析，确定了化合物 1-3 中 HMG 片段的绝对构型为 S。采用脂多糖诱导的 RAW264.7 细胞评价了化合物 1-5 的 NO 抑制活性。在 10µM 时，化合物 1-5 对 RAW264.7 细胞没有细胞毒性。