A stereoselective and highly practical synthesis of cytosolic phospholipase A(2) substrate, 2-S-arachidonoyl-1-O-hexadecyl-sn-2-thioglycero-3-O-phosphocholine

被引：8

作者：

Fuji, M ^{[1
]}

Watanabe, F ^{[1
]}

Fujii, Y ^{[1
]}

Hashizume, H ^{[1
]}

Okuno, T ^{[1
]}

Shirahase, K ^{[1
]}

Teshirogi, I ^{[1
]}

Ohtani, M ^{[1
]}

机构：

[1] SHIONOGI & CO LTD,SHIONOGI RES LABS,FUKUSHIMA KU,OSAKA 553,JAPAN

来源：

JOURNAL OF ORGANIC CHEMISTRY | 1997年 / 62卷 / 20期

关键词：

D O I：

10.1021/jo970882t

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

The substrate 1 of cytosolic phospholipase A(2) (cPLA(2)) is an ether-type thiophospholipid with arachidonic acid at the C-2 position and is required for the chromogenic assay for reliable and convenient high throughput screening. The original method of synthesis of 1 has significant problems, resulting in extremely low overall yield and purity. We developed a novel and highly practical method of preparing sufficient quantities of pure 1 for assay. Our synthetic sequence is started with commercially available 1,2-O-isopropylidene-sn-grycerol (5) and is based on the following key steps: trityl migration reaction of 10 with boron trifluoride etherate to form 13, phosphocholine-forming reaction of 13 to yield 15, and efficient conversion of 15 into 1 by deprotection of a trityl group and condensation with arachidonic acid. Our method offers a practical means of large-scale production of 1 with excellent high chemical purity, because of the introduction of arachidonic acid at the last step of the synthetic sequence.

引用

页码：6804 / 6809

页数：6

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