Glyceroamidothiophosphates of cholecalciferol (Vitamin D₃)

Abstract

The hexamethyltriamide of phosphorous acid activated by the addition of iodine at the optimum molar ratio 1.05∶0.05 was used as a phosphorylating reagent to synthesize cholecalciferyl‐3‐0‐(N,N‐dimethylamido)thiophosphate derivatives of 1,3‐benzylidene‐rac‐glycerol, 1,2‐isopropylidene‐rac‐glycerol, 1,3‐dioleoyl‐rac‐glycerol, and 1,2‐dioleoyl‐rac‐glycerol in a one‐pot procedure in high overall yields (81–86%). The compounds represent new model types of phospholipid structures which, in addition to glycerol and a steroid fragment, contain a biologically important linkage other than an oxygen‐phosphorus bond.

Triester glycerothiophosphates of cholecalciferol (vitamin D3)

“…The scheme shows for a, la, lab, lac, labdS, lacdS, laceS, labfS, and lab'S: R ~ = cholecalciferyl; b, lab, labdS, labfS, and lab2S: R ~ {or R 8) = 1,2-isopropylidene-rac-glyceryl; c, lac, lacdS, and laceS: R 2 = 1,2-dipalmltoyl-rac-glyceryl; d, labdS, and lacdS: R 3 --methyl; e and laceS: R 3 = 2-dlmethylAmlnoethyl; f and labfS: R 3 = 3-dimethylami-opropyl. This was proven earlier by transformation of the phosphite la to the corresponding thiophosphate derivative (2).…”

“…The high selectivity of phosphorylation at the monc~ ester formation stage permits the synthesis of asymmetrical diesters in a "one-pot" procedur~ The bis{N,Ndimethylamido)phosphite la was used as the initial key intermediate in order to avoid transesterification under experimental conditions. The crude intermediate la was treated with an equivalent amount of the glycerol derivatives b or c at 70~ for 1.5 l~ In preliminary studies we established that this type of diester phosphite also can ( 20-25eC, c6H 6) 0veroll yields: 60-80% lob, Ioc be obtained directly in high yields (2). The consecutive treatment of an equimolar mixture of the third substrate b, d, e or f, imidazole and carbon disulfide with an equivalent amount of the crude diester intermediate lab or lac and sulfur at room temperature for 2-4 h or 30 min, respectively, afforded the triester thiophosphates labdS, lacdS, laceS, labfS and lab2S in good overall yields.…”

Racemic Phospholipids for Origin of Life Studies

“…The last steps for the preparation of the target compounds 1a-2c were performed accordingly to the reported synthetic procedures. Yields and purity were higher with respect to any reported data (Appendix A) [39,42,43,45,50,55]. We also produced GVs made of (R)-POPC, rac-POPC and a scalemic mixture (scal-POPC) made of (R:S = 2:1) POPC enantiomers (Figures 2 and 3).…”

Diacetone‐D‐glucosyl‐3‐O‐(N,N‐diethylamido)‐thiophosphates of the lipid‐soluble vitamins D2, D3 and E

“…It is well known that the phosphorylation of lipids by phosphorus oxychlorid~ chlorophosphates and other conventional reagents can frequently be accompanied by side reactions, ag., nucleophilic substitution at the carbon with the phosphatoxyl group, molecular rearrangements, eliminations, eta (5). Use of acyclic triamides of phosphorous acid after activation with iodine avoids these problems (5,7,8). In the present study, the tris(N,N-diethyl)amide of phosphorous acid 1 (Schemes 1, 2 and 3) with iodine at an optimal molar ratio of 1.05:0.05 was used as reagent.…”

“…Although lipid-soluble D and E vitamins are considered essential for living organisms, their physiological functions have still not been conclusively determined. As a result, the synthesis of new phospholipids from steroids and tocopherols that can be used as models has received increasing attention in recent years (1)(2)(3)(4)(5)(6)(7). The synthesis of derivatives in which a carbohydrate fragment and a lipid-soluble vitamin are structurally linked has not yet been considered.…”