Synthesis of sulfur-containing glycerophospholipids

Surfactant for Pediatric Acute Lung Injury

“…Ester-linked glycerophospholipids of the kind found in native surfactant are the primary lipids used in current synthetic exogenous surfactants. However, synthetic ether-linked lipids are now available that have direct structural analogy to lung surfactant lipids plus designed molecular behavior that enhances adsorption and spreading while maintaining very high dynamic surface tension lowering in surface films (e.g., [71,[205][206][207][208][209][210][211]). Moreover, such lipids have structural features making them resistant to phospholipases such as phospholipase A 2 , which has been implicated in the pathology of ALI/ARDS [65,[212][213][214][215][216][217][218].…”

“…Phospholipase-induced degradation of lung surfactant glycerophospholipids not only reduces the concentration of active components, but also generates reaction products such as lysophosphatidylcholine and fluid free fatty acids that can further decrease surface activity by interacting biophysically with remaining surfactant at the alveolar interface [55,59,70]. Synthetic exogenous surfactants containing such phosphonolipids combined with purified surfactant proteins or synthetic peptides have very high overall surface activity plus an ability to resist phospholipases in ALI/ARDS [71,[208][209][210][211]219]. On-going basic research is continuing to design and synthesize peptides related to SP-B and other surfactant proteins for use in highly-active fully-synthetic exogenous surfactants in combination with either normal glycerophospholipids or phospholipase-resistant analogs.…”

Novel Phospholipase-Resistant Lipid/Peptide Synthetic Lung Surfactants

“…The synthesis, purification, and biophysical behavior of several novel phospholipase-resistant phosphonolipids having potential utility as constituents in synthetic lung surfactants has been reported [33][34][35][36][37][38][39][40][41][42][43][44][45][46]. Two extremely surfaceactive C16:0 phosphonolipid analogs identified in these studies are DEPN-8 [34,[36][37][38][39][40][41][42]44] and SO 2 -lipid [43][44][45] (Fig.…”

“…Thus, DEPN-8 has the ability to reduce surface tension to <1 mN/m in compressed surface films, while having superior adsorption and film respreading behavior compared to DPPC [34,[36][37][38]. SO 2 -lipid also reaches very low surface tensions in compressed interfacial films while having improved adsorption and film respreading over DPPC [43][44][45]. Structural resistance to phospholipases A 1 , A 2 , and D in phosphonolipid analogs does not prevent these compounds from being taken up and utilized in lung surfactant recycling pathways in alveolar type II epithelial cells [1,40,47], and exogenous surfactants containing DEPN-8 do not have short-term pulmonary toxicity in animals [40].…”

A novel synthetic approach to glycerophospholipids via Horner–Wadsworth–Emmons reaction of mixed phosphonoacetate

“…[8][9][10][11] Chemical synthesis of natural and unnatural glycerophospholipids has recently attracted much attention because of their variety of biological activities. [12][13][14][15][16][17][18][19][20][21][22] In some cases, however, the amphipathic property of glycerophospholipids, which is attributed to their hydrophilic region (a phosphorylated alcohol moiety) and hydrophobic region (a diacylglycerol moiety), causes difficulties in the handling of these compounds and their precursors during their organic synthesis.…”