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

The aim of this research was to design and synthesize new lipid conjugates of 7-DHC that could serve as a new storage form of esterified provitamin D, increasing the reservoir of this biomolecule in the epidermis and enabling controlled production of vitamin D even during periods of sunlight deficiency. Acylglycerol and glycerophospholipid containing succinate-linked provitamin D at the -2 position of the glycerol backbone were synthesized from dihydroxyacetone (DHA) and -glycerophosphocholine (GPC), respectively. The three-step synthesis of 1,3-dipalmitoyl-2-(7-dehydrocholesterylsuccinoyl)glycerol involved the esterification of DHA with palmitic acid, reduction of the carbonyl group, and conjugation of the resulting 1,3-dipalmitoylglycerol with 7-dehydrocholesterol hemisuccinate (7-DHC HS). The use of NaBHCN as a reducing agent was crucial to avoid acyl migration and achieve the final product with 100% regioisomeric purity. For the preparation of 1-palmitoyl-2-(7-dehydrocholesterylsuccinoyl)--glycero-3-phosphocholine, a two-step process was applied, involving the esterification of GPC at the -1 position with palmitic acid, followed by the conjugation of 1-palmitoyl--glycero-3-phosphocholine with 7-DHC HS. Alongside the main product, a small amount of its regioisomer with provitamin D linked at the -1 position and palmitic acid at the -2 position was detected, indicating acyl migration from the -1 to the -2 position in the intermediate 1-palmitoyl-glycerophosphocholine. The synthesized novel lipids were fully characterized using spectroscopic methods. They can find applications as novel lipid-based prodrugs as additives to sunscreen creams.