2-Deoxy-2,2-difIuoro-D-erythro-pentonic acid gamma-lactone-3,5-dibenzate is an intermediate in the synthesis of gemcitabine hydrochloride. Gemcitabine hydrochloride is a new synthetic difluoronucleoside antimetabolite antitumor drug, which was first developed by EliLilly Company in the United States.
As a prodrug, gemcitabine is a good substrate for deoxythymidine kinase phosphorylation in cells, and is converted into the following metabolites by the action of the enzyme: gemcitabine monophosphate (dFdCMP), gemcitabine diphosphate (dFdCDP) and gemcitabine triphosphate Phosphate (dFdCTP) of which dFdCDP and dFdCTP are active products. dFdCDP inhibits ribonucleotide reductase, thereby reducing the amount of deoxynucleotides (especially dCTP) required for the repair of DNA synthesis, low levels of dCTP reverse the normal negative feedback inhibition of deoxyside kinase, resulting in more dFdCTP accumulation. At the same time, dFdCDP inhibited the deamination of dFdCMP by dCTP-induced deoxycytase, and dFdCTP directly inhibited deoxycytidine dehydration, so that more dFdCMP was converted into the deamination of the active metabolite dFdCMP, and dFdCTP directly inhibited deoxycytidine deamination. Cytidine deaminase, which converts more dFdCMP into the active metabolite dFdCDP, dFd-CTP and dFdCTP competes with dCTP for binding to the DNA strand, inserts into the DNA strand at the site of deoxycytidine, and allows guanosine to interact with it When paired, the gemcitabine molecule is "masked" by this guanosine from removal and repair by exonuclease, and then DNA strand synthesis stops, resulting in DNA breakage and cell death.
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