A NEW, ASYMMETRIC-SYNTHESIS OF LIPIDS AND PHOSPHOLIPIDS
A NEW, ASYMMETRIC-SYNTHESIS OF LIPIDS AND PHOSPHOLIPIDS
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DOI：
10.1021/jo00231a025
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发表时间：
1987-10-30
影响因子：
3.6
通讯作者：
JOHNSON, RA
中科院分区：
文献类型：
--
作者：
BURGOS, CE;AYER, DE;JOHNSON, RA
用硬脂酸对（S）-缩水甘油（2）进行钛辅助的亲核开环，得到（S）-（+）-1-硬脂酰基-sn-甘油（3）。可以用叔丁基二甲基氯硅烷进行3的甲硅烷基化以选择性地形成（R）-（+）-1-硬脂酰基-3-（叔丁基二甲基甲硅烷基）-sn-甘油（4）。4与（S）-（+）-α-的酯化methoxy-.alpha.（三氟甲基）苯乙酰氯得到“Mosher酯”（5），其高场NMR谱适合于测定对映体过量。4与硬脂酰氯酯化，然后除去甲硅烷基保护基，得到二酰基甘油酯（S）-（-）-1，2-二硬脂酰-sn-甘油（7）。通过使用N-溴代琥珀酰亚胺/DMSO/THF/H2O进行水解，可以在没有酰基迁移的情况下除去甲硅烷基。文献方法可用于完成磷酸胆碱头基的组装。这种短的合成路线提供了一个新的入口，光学活性磷脂和单，二，三酰甘油酯的合成。
Titanium-assisted nucleophilic opening of (S)-glycidol (2) with stearic acid gives (S)-(+)-1-stearoyl-sn-glycerol (3). Silylation of 3 with tert-butyldimethylchlorosilane can be done to selectively form (R)-(+)-1-stearoyl-3-(tert-butyldimethylsilyl)-sn-glycerol (4). Esterification of 4 with (S)-(+)-.alpha.-methoxy-.alpha.(trifluoromethyl)phenylacetyl chloride gives a "Mosher ester" (5) whose high-field NMR spectrum is suitable for determination of enantiomeric excess. Esterification of 4 with stearoyl chloride followed by removal of the silyl protecting group gives the diacylglyceride, (S)-(-)-1,2-distearoyl-sn-glycerol (7). The silyl group may be removed without acyl migration by the use of N-bromosuccinimide/DMSO/THF/H2O for the hydrolysis. Literature methods may be used to complete the assembly of the phosphorylcholine head group. This short synthetic route offers a new entry to the synthesis of optically active phospholipids and mono-, di-, and triacylglycerides.