Synthesis of lysophospholipids

Abstract

New synthetic methods for the preparation of biologically active phospholipids and lysophospholipids (LPLs) are very important in solving problems of membrane-chemistry and biochemistry. Traditionally considered just as second-messenger molecules regulating intracellular signalling pathways, LPLs have recently shown to be involved in many physiological and pathological processes such as inflammation, reproduction, angiogenesis, tumorogenesis, atherosclerosis and nervous system regulation. Elucidation of the mechanistic details involved in the enzymological, cell-biological and membrane-biophysical roles of LPLs relies obviously on the availability of structurally diverse compounds. A variety of chemical and enzymatic routes have been reported in the literature for the synthesis of LPLs: the enzymatic transformation of natural glycerophospholipids (GPLs) using regiospecific enzymes such as phospholipases A1 (PLA1), A2 (PLA2) phospholipase D (PLD) and different lipases, the coupling of enzymatic processes with chemical transformations, the complete chemical synthesis of LPLs starting from glycerol or derivatives. In this review, chemo-enzymatic procedures leading to 1- and 2-LPLs will be described.

Figure 1

Structures of phospholipids and derivatives.

Figure 2

Structure of 2-lysophosphatidylcholine.

Figure 3

Structure of 2-lysophosphatidic acid and sphingosine-1-phosphate.

Figure 4

C-3 Building blocks (1a-e) and phosphorylating agents (2a-2g) most commonly used for the assembly of LPLs.

Figure 5

Synthesis of 2-LPC from D-mannitol.

Figure 6

Efficient synthesis of 2-LPA starting from (S)-glycidol (10).

Figure 7

Synthesis of 2-LPC from (S)-glycidol.

Figure 8

A stereospecific synthesis of LPC starting from glyceric acid.

Figure 9

Synthesis of 2-LPC from p-nitrophenylglycerate.

Figure 10

Synthesis of 2-LPC starting from 3-p-toluenesulfonyl-sn-glycerol.

Figure 11

Tin-mediated synthesis of 2-LPC from natural lecithins.

Figure 12

Enzymes acting on phospholipids and their specific site of action.

Figure 13

Phospholipases/Lipases catalyzed transformations of phospholipids.

Figure 14

Chemo-enzymatic transformations of natural lecithins into 2-lysophospholipids.

Figure 15

Mechanism for the PLD-catalyzed hydrolysis and transphosphatidylation of 2-LPC with PLD.