Novel Lipid-Based Carriers of Provitamin D<sub>3</sub>: 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<sub>3</sub>, increasing the reservoir of this biomolecule in the epidermis and enabling controlled production of vitamin D<sub>3<...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-12-01
|
| Series: | Molecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1420-3049/29/23/5805 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Summary: | 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<sub>3</sub>, increasing the reservoir of this biomolecule in the epidermis and enabling controlled production of vitamin D<sub>3</sub> even during periods of sunlight deficiency. Acylglycerol and glycerophospholipid containing succinate-linked provitamin D<sub>3</sub> at the <i>sn</i>-2 position of the glycerol backbone were synthesized from dihydroxyacetone (DHA) and <i>sn</i>-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 NaBH<sub>3</sub>CN 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)-<i>sn</i>-glycero-3-phosphocholine, a two-step process was applied, involving the esterification of GPC at the <i>sn</i>-1 position with palmitic acid, followed by the conjugation of 1-palmitoyl-<i>sn</i>-glycero-3-phosphocholine with 7-DHC HS. Alongside the main product, a small amount of its regioisomer with provitamin D<sub>3</sub> linked at the <i>sn</i>-1 position and palmitic acid at the <i>sn</i>-2 position was detected, indicating acyl migration from the <i>sn</i>-1 to the <i>sn</i>-2 position in the intermediate 1-palmitoyl<i>-sn</i>-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. |
|---|---|
| ISSN: | 1420-3049 |