Novel Lipid-Based Carriers of Provitamin D3: Synthesis and Spectroscopic Characterization of Acylglycerol Conjugated with 7-Dehydrocholesterol Residue and its Glycerophospholipid Analogue

Two novel lipids, acylglycerol and glycerophospholipid containing succinate-linked provitamin D3 at sn-2 position of glycerol backbone, have been synthesized from dihydroxyacetone (DHA) and sn-glycerophosphocholine (GPC), respectively. Three-step synthesis of 1,3-dipalmitoyl-2-(7-dehydrocholesterylsuccinoyl)glycerol involved esterification of DHA with palmitic acid, reduction of carbonyl group and conjugation of resulting 1,3-dipalmitoylglycerol with 7-dehydrocholesterol hemisuccinate (7-DHC HS). Using NaBH3CN as a reducing agent was crucial to avoid any acyl migration and obtain the final product with 100% regioisomeric purity. 1-Palmitoyl-2-(7-dehydrocholesterylsuccinoyl)-sn-glycero-3-phosphocholine was produced in two-step process by the esterification of GPC at sn-1 position with palmitic acid and subsequent conjugation of 1-palmitoyl-sn-glycero-3-phosphocholine with 7-DHC HS. Apart from the main product, some amount of its regioisomer containing provitamin D3 linked at sn-1 position and palmitic acid at sn-2 position was detected which indicated the acyl migration of palmitic acid from sn-1 to sn-2 position in the intermediate 1-palmitoyl-sn-glycerophosphocholine. Synthesized novel lipids were fully characterized by spectroscopic data. They can find application as novel lipid-based prodrugs as the additives to sunscreen creams, providing controlled release of provitamin D3 in the epidermis.