Simple synthesis of diastereomerically pure phosphatidylglycerols by phospholipase D-catalyzed transphosphatidylation
Simple synthesis of diastereomerically pure phosphatidylglycerols by phospholipase D-catalyzed transphosphatidylation
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DOI：
10.1007/s11745-004-1326-z
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发表时间：
2004-10-01
期刊：
影响因子：
1.9
通讯作者：
Kuksis, A
中科院分区：
文献类型：
--
作者：
Sato, R;Itabashi, Y;Kuksis, A
建立了一种合成非对映异构体纯磷脂酰甘油（PtdGro）的简单方法，即1,2-二酰基-sn-甘油-3-磷酸-3'-sn-甘油（R，R构型）和1,2-二酰基-sn-甘油-3-磷酸-1'-sn-甘油（R，S构型）。为此，利用放线瘤菌属（Actinomadura sp.）的1,2-二酰基- n-甘油-3-磷脂胆碱（PtdCho）和对映体1,2- o-异丙基甘油（1,2- o-异丙基甘油）与磷脂酶D （PLD）进行转磷脂酰化，制备了非对映体1,2- o-异丙基PtdGro。选择该物种是因为其转磷脂酰化活性较高，磷脂酸（PtdOH）生成量较其他链霉菌属的PLD低。在由乙醚和乙酸酯缓冲液组成的双相体系中，反应进行得很顺利，几乎没有PtdCho水解成PtdOH。在硼酸存在下，将异丙基PtdGro非对映体在三甲基硼酸中加热至100℃，去除异丙基保护基团，得到所需的PtdGro非对映体。产品的纯度由手性相高效液相色谱法测定，完全依赖于所用原始异丙酯的光学纯度。本方法简单，可用于合成具有饱和和不饱和酰基链的纯PtdGro非对映体。
A simple method for synthesizing diastereomerically pure phosphatidylglycerols (PtdGro), namely, 1,2-diacyl-sn-glycero-3-phospho-3'-sn-glycerol (R,R configuration) and 1,2-diacyl-sn-glycero-3-phospho-1'-sn-glycerol (R,S configuration), was established. For this purpose, diastereomeric 1,2-O-isopropylidene PtdGro were prepared from 1,2-diacyl-sn-glycero-3-phosphocholine (PtdCho) and enantiomeric 1,2-O-isopropylideneglycerols by transphosphatidylation with phospholipase D (PLD) from Actinomadura sp. This species was selected because of its higher transphosphatidylation activity and lower phosphatidic acid (PtdOH) formation than PLD from some Streptomyces species tested. The reaction proceeded well, giving almost no hydrolysis of PtdCho to PtdOH in a biphasic system consisting of diethyl ether and acetate buffer at 30degreesC. The isopropylidene protective group was removed by heating the diastereomeric isopropylidene PtdGro at 100degreesC in trimethyl borate in the presence of boric acid to obtain the desired PtdGro diastereomers. The purities of the products, which were determined by chiral-phase HPLC, were exclusively dependent on the optical purities of the original isopropylideneglycerols used. The present method is simple and can be utilized for the synthesis of pure PtdGro diastereomers having saturated and unsaturated acyl chains.