Department of Drug Design and Pharmacology, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark.
School of Pharmacy and Medical Sciences, University of South Australia, Frome Road, Adelaide 5000, Australia.
J Nat Prod. 2020 May 22;83(5):1598-1610. doi: 10.1021/acs.jnatprod.0c00070. Epub 2020 Apr 7.
Ten new branched-chain fatty acid (BCFA) dimers with a substituted cyclohexene structure, five new monomers, and two known monomers, (2,4,6)-5-(acetoxymethyl)tetradeca-2,4,6-trienoic acid and its 5-hydroxymethyl analogue, were identified in the leaf extract of subsp. using a combination of HPLC-PDA-HRMS-SPE-NMR analysis and semipreparative-scale HPLC. The dimers could be classified as three types of Diels-Alder reaction products formed between monomers at two different sites of unsaturation of the dienophile. Two of the monomers represent potential biosynthetic intermediates of branched-chain fatty acids. Several compounds were found by high-resolution bioactivity profiling to inhibit PTP1B and were purified subsequently by semipreparative-scale HPLC. The dimers were generally more potent than the monomers with IC values ranging from 2 to 66 μM, compared to 38-484 μM for the monomers. The ten fatty acid dimers represent both a novel class of compounds and a novel class of PTP1B inhibitors.
利用 HPLC-PDA-HRMS-SPE-NMR 分析和半制备规模 HPLC 的组合，从亚种的叶提取物中鉴定出 10 种具有取代环己烯结构的新型支链脂肪酸 (BCFA) 二聚体、5 种新型单体和 2 种已知单体，（2,4,6）-5-（乙酰氧基甲基）十四烷-2,4,6-三烯酸及其 5-羟甲基类似物。二聚体可以分为三种类型的 Diels-Alder 反应产物，这些产物是在双烯体不饱和的两个不同部位之间形成的单体之间形成的。两种单体代表支链脂肪酸生物合成的潜在中间产物。通过高分辨率生物活性分析发现，几种化合物可以抑制 PTP1B，随后通过半制备规模的 HPLC 进行纯化。与单体的 IC 值为 38-484 μM 相比，二聚体通常比单体更有效，其 IC 值范围为 2-66 μM。这 10 种脂肪酸二聚体代表了一类新型化合物和一类新型 PTP1B 抑制剂。
