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Efficient Stereoselective Synthesis of Plasmenylcholines
Author(s) -
Rui Yuanjin,
Thompson David H.
Publication year - 1996
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.19960021205
Subject(s) - yield (engineering) , chemistry , imidazole , stereoselectivity , acylation , pyridine , ether , stereochemistry , medicinal chemistry , organic chemistry , catalysis , materials science , metallurgy
The first practical total chemical synthesis of a plasmenylcholine (1– O ‐1'‐( Z )‐hexadecenyl‐2‐hexadecanoyl‐ sn ‐glycero‐3‐phosphocholine) with pure ( Z ) olefin stereochemistry is reported. Monopalmitin was doubly protected as the 3‐TBDPS‐2‐TBDMS ethers ( tert ‐butyldiphenylsilyl‐, tert ‐butyldimethylsilyl‐) and converted to the corresponding 1‐ O ‐1′‐( Z )‐hexadecenyl‐2‐TBDMS‐3‐TBDPS‐glyceryl ether (by the method of ref. [43]). Clean deprotection with tetra‐butylammonium fluoride in the presence of imidazole gave 1‐ O ‐1′‐( Z )‐hexadecenylglycerol in >90% yield. Resilylation with TBDPSCl followed by acylation of the sn ‐2 alcohol with palmitoyl chloride and deprotection of the resulting 3‐TBDPS‐2‐hexadecanoyl‐1– O ‐1′‐( Z )‐hexadecenylglycerol at –20°C with Bu 4 NF gave 2‐hexadecanoyl‐1– O ‐1′‐( Z )‐hexadecenylglycerol in 86% yield. The 3‐phosphocholine group was attached by phosphorylating the free hydroxyl with 2‐chloro‐2‐oxo‐1,3,2‐dioxaphospholane in the presence of pyridine, instead of Et 3 N, as base to avoid acyl migration; the dioxaphospholane triester intermediate was subsequently cleaved with Me 3 N to give 1‐ O ‐1′‐( Z )‐hexadecenyl‐2‐hexadecanoyl‐ sn ‐glycero‐3‐phosphocholine in 18% overall yield from monopalmitin. The efficiency and flexibility of this route makes it well‐suited to the preparation of a wide variety of 1‐, 2‐, and 3‐substituted as well as isotopically labeled plasmenylcholines for biophysical and biochemical studies.