A Rapid Condensation between Lysophosphorylcholine and Fatty Acids with an Easily Separable Amine Base

Abstract

With 2,6-Cl₂C₆H₃COCl and 1-methylimidazole, the title condensation completed at room temperature within 12 hours, which is shorter time than that with the standard DCC/DMAP system. Use of easily separable 1-methylimidazole from the crude product by chromatography is an additional advantage of the present reagent system.

Key words

carboxylic acids - condensation - esterification - furans - lipids

References

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12

The racemic lyso-PC 1 was conveniently prepared from racemic glycidol in two steps according to the literature procedure: [9] (i) POCl₃ then [HO(CH₂)₂NMe₃]⁺·TsO^-; (ii) C₁₅H₃₁CO₂Cs.

14

Due to the low solubility of lyso-PC 1, THF was omitted in the preliminary study using 4.

15

Reaction was carried out until 1 was consumed completely by ¹H NMR spectroscopy since separation of product 3a and remaining 1 by chromatography on silica gel by using a CH₂Cl₂-MeOH mixture as an eluent was quite difficult. TLC analysis was useless for monitoring the progress of reaction.

16

The R _f values of compounds (Merck Silica gel 60 F₂₅₄, MeOH): 1, 0.1-0.2; 2a-e, >0.8; 3a, 0.1-0.2; 3b, 0.1-0.2; 3c, 0.1-0.2; 3d, 0.2; 3e, 0.2; 3f, 0.2; DMAP, 0.1-0.15;
1-methylimidazole, 0.5; 1-butylimidazole, 0.6; and
1-benzylimidazole, 0.6.

17

Chromatography of a reaction mixture on silica gel was conducted with CH₂Cl₂-MeOH (CH₂Cl₂ only, then 5:1, finally 1:3). Excess 2a eluted very early, then DMAP, followed rapidly by product 3a, though DMAP was slightly more polar than 3a on TLC. Other by-product(s) derived from the acid chloride (or simply the hydrolyzed acid) did not interfere with the purification of 3a. In addition, CH₂Cl₂-MeOH is a convenient solvent system for chromatography in comparison with conventional CHCl₃-MeOH-H₂O because of fast elution during chromatography, easy evaporation of the eluent, and no contamination of silica gel impurity that is frequently encountered with the latter solvent system.

18

Confer condensation of acyl imidazolide and lysophophorylcholines, see ref. 5.