Mass spectrometry-directed structure elucidation and total synthesis of ultra-long chain (O-acyl)-ω-hydroxy fatty acids
Mass spectrometry-directed structure elucidation and total synthesis of ultra-long chain (O-acyl)-ω-hydroxy fatty acids
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DOI：
10.1194/jlr.m086702
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发表时间：
2018-08-01
影响因子：
6.5
通讯作者：
Blanksby, Stephen J.
中科院分区：
文献类型：
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作者：
Hancock, Sarah E.;Ailuri, Ramesh;Blanksby, Stephen J.
（O-酰基）-ω-羟基脂肪酸（OAHFA）包括一种不寻常的脂质亚类，存在于皮肤、皮脂和睑板腺分泌物中。尽管它们在结构上与羟基FA的FA酯（FAHFA）的一般类别相关，但超长链（30-34个碳）和主链羟基FA的推定ω-取代表明OAHFA具有独特的生物化学。OAHFA的完整结构解析一直具有挑战性，因为它们在复杂的脂质基质中的丰度低。此外，由于这些化合物以密切相关的异构体的混合物形式存在，因此获得的光谱数据不足以通过全合成来指导结构确认。在这里，我们描述了通过多级MS和新型多维离子活化方法利用脂质的气相纯化从人睑脂中提取的超长链OAHFA的完整分子结构。该分析阐明了不饱和位点、碳-碳双键的立体化学构型和酯键区域化学。这种异构体分辨的MS指导了超长链OAHFA的第一次全合成，这反过来证实了在人睑脂中发现的最丰富的OAHFA的结构，OAHFA 50：2。合成OAHFA的可用性为未来研究这些脂质独特的生物物理和生化特性开辟了新领域。
The (O-acyl)-omega-hydroxy FAs (OAHFAs) comprise an unusual lipid subclass present in the skin, vernix caseosa, and meibomian gland secretions. Although they are structurally related to the general class of FA esters of hydroxy FAs (FAHFAs), the ultra-long chain (30-34 carbons) and the putative omega-substitution of the backbone hydroxy FA suggest that OAHFAs have unique biochemistry. Complete structural elucidation of OAHFAs has been challenging because of their low abundance within complex lipid matrices. Furthermore, because these compounds occur as a mixture of closely related isomers, insufficient spectroscopic data have been obtained to guide structure confirmation by total synthesis. Here, we describe the full molecular structure of ultra-long chain OAHFAs extracted from human meibum by exploiting the gas-phase purification of lipids through multi-stage MS and novel multidimensional ion activation methods. The analysis elucidated sites of unsaturation, the stereochemical configuration of carbon-carbon double bonds, and ester linkage regiochemistry. Such isomer-resolved MS guided the first total synthesis of an ultra-long chain OAHFA, which, in turn, confirmed the structure of the most abundant OAHFA found in human meibum, OAHFA 50:2. The availability of a synthetic OAHFA opens new territory for future investigations into the unique biophysical and biochemical properties of these lipids.