Synthesis And Bioactivity Of Vitamin D₂ Derivatives Modified By Amino Acids

Structures of vitamin D2 derivative have a close relationship to biological activity. Chemical modification of vitamin D2 has always been one of the hot research topics of vitamin D2. In this paper,10 kinds of new vitamin D2 derivatives were synthesized by chemical modification, and some anticancer activity of of them were preliminarily explored.First of all, we used vitamin D2 as raw material to prepare the key intermediates 3.4 by potassium permanganate oxidation, lead tetraacetate oxidation, sodium borohydride reduction; Based on the principle of active group splicing, we took vitamin D2 or compound 3.4 as raw material with Boc-L-amino acids to prepare 4 kinds of vitamin D2 derivatives with L- amino acid modifying A ring and 4 kinds of of vitamin D2 derivatives with L- amino acids replacing the A ring through Steglich esterification, Lewis acid (or TFA) catalyzing N-Boc deprotection. Secondly, Two C-glycosides were prepared by C- glycosidation, acylation and aldol reaction catalyzed by Proline-DIPEA from D-glucose, then the two C-glycosides were esterified with vitamin D2 succinate to give two potential pharmacodynamic vitamin D2 derivatives. Particularly, compared to the literature reported, the catalysis effect of proline-DIPEA for aldol reaction was obvious; for instance, it has the advantage of fast rates and high yields, which has not been reported by literature.In the end, we investigated the antitumor activity of some title compounds by MTT method, and the inhibition rate of human hepatocellular carcinoma cell (Hep G2), and human breast cancer cells (MCF-7) were tested in different concentrations. From the results, We found that some of the compounds exhibited good activity; in particular, compound 2.4d exhibited better antitumor activity against human hepatocellular carcinoma cell (Hep G2), and compound 2.4a exhibited better antitumor activity against human breast cancer cell (MCF-7).