Cytidine 5 -fluoro

RN 154361-50-9 MF CijHzzFNjO MW 359.35 CN 5 -Deoxy-5-fluoro-A -[(pentyloxy)carbonyl]cytidine... 

C27H42FN3O10 174667-24-4) see Capecitabine 5 -deoxy-5-fluoro-A-[(pentyloxy)carbonyl]cytidine 2, 3 -diacetate... 

A-Acetyl-9-deoxy-9-fluoroneuraminic acid (591) was prepared by treatment of a protected 6-hydroxyl precursor with A, A-diethylaminosulfur trifluoride (DAST) or through condensation of 2-acetamido-2,6-dideoxy-6-fluoro-D-mannopyranose with potassium di(/ >r/-butyl) oxaloacetate. Compound 591 is a substrate for cytidine monophosphate (CMP)-sialic acid synthetase, giving rise to CMP-5-A-acetyl-9-deoxy-9-fluoroneuraminic acid, which is cytotoxic against tumor cells. 5-A-Acetyl-3-fluoroneuraminic acids 592-594 were prepared through fluorine (or acetyl hypofluorite) addition (in AcOH) to methyl 5-acetamido-4,7,8,9-tetra-0-acetyI-2,6-anhy-dro-2,3,5-trideoxy-D- /ycm>D- a/arto-non-2-enopyranosate. Compound 592 was found to be a potent neuraminidase inhibitor. 

The susceptibilities of some of these fluorinated purine nucleosides to the action of enzymes are now described. In contrast to the inertness of the 2 -deoxy-2 -fluoro- and 3 -deoxy-3 -fluorocytidine analogs 739, 744, and 821 towards cytidine deaminase, the adenosine compounds 867, 883, and 906 are readily deaminated - by the adenosine deaminase in erythrocytes and calf intestine, but the resulting (deaminated) inosine compounds (from 867 and 883), as well as 888, are highly resistant - to cleavage by purine nucleoside phosphorylase (to give hypoxanthine base for the first two). The reason was discussed. Both 867 and 883 can form the 5 -triphosphates, without deamination, in human erythrocytes or murine sarcoma cells in the presence of 2 -deoxycoformycin, an adenosine deaminase inhibitor, but... 

Figure 5 Dideoxynucleoside (ddN) analogues 2, 3 -dideoxycytidine (DDC), 3 -azido-2, 3 -dideoxythymidine (AZT), 3 -fluoro-2, 3 -dideoxythymidine (FLT), 2, 3 -didehydro-2, 3 -dideoxythymidine (D4T), 3 -thia-2, 3 -dideoxycytidine (3TC), 3 -thia-2, 3 -dideoxy-5-fluorocytidine (FTC), and 2, 3 -dideoxy-L-cytidine (l-DDC).

Tezacitabine is synthesized from the cytidine protected at 4 -OH, 5 -OH and 4-NH2. Swern oxidation provides a ketone, which is converted to a gem-fluoro-sulfonyl olefin with the anion of sulfonylfluorophosphonate. Reduction of the sulfonyl group is achieved with BusSnH (Fig. 33) [92]. 

Condensation of LXVIa (R = p-toluyl) with monomercurithymine (prepared from 1-acetylthymine) produces a mixture of acylated nucleoside anomers (LXVlb and LXVIc, R = thyminyl) which are separated and de-esterified to thymidine and a-thymidine. Similarly, reaction of N-acetylcytosinemercury (LV) with LXVIa (R = p-chlorobenzoyl) yields the a and ft anomers of acylated 2-deoxycytidine which, after separation and deacylation, are converted smoothly to 2-deoxycytidine (LXVlb, R = H, R = cytosinyl) and its a anomer (LXVIc). In like manner, 2-deoxy-5 -fluoro-uridine and -cytidine were synthesized, along with their... 

Deoxy-5-fluoro-N4-((n-pentyloxy)carbonyl)cytidine may be prepared according to US Patent No. 6,114,520. 

From 2, 3 -bis-0-(tert-butyldimethylsilyl)-5 -deoxy-5-fluorocytidine and n-pentylchloroformate in dichloromethane and pyridine may be obtained 2, 3 -bis-0-(tert-butyldimethylsilyl)-5 -deoxy-5-fluoro-N4-((pentyloxy)carbonyl) cytidine.From 2, 3 -bis-0-(tert-butyldimethylsilyl)-5 -deoxy-5-fluoro-N4-((pentyloxy)carbonyl)cytidineand tetrabutylammonium fluoride in tetrahydrofuran at room temperature for 2 hours may be prepared the product which by hydrolyses may be converted to 5-deoxy-5-fluoro-N4-((pentyloxy)carbonyl)cytidine. Purification of the product may be carried out by silica gel chromatography (using dichloromethane methanol = 20 1 as an eluent). 

Metabolic pathway of capecitabine to 5-FU. 5-DFCR = 5 -deoxy-5-fluoro-cytidine 5-DFUR = 5 -deoxy-5-fluorouridine... 

Figure 4 Catalytic activation of cytosine for C5-methylation by nucleophilic addition of a thiolate at the C6 position, (a) The chemical mechanism of enzymatic DNA cytosine-S methylation. Mechanism-based inhibition of DMA MTases by cytidine analogs 5-fluoro-2 -deoxycytidine (b), 5-aza-2 -deoxy-cytidine (c), and 2-pyrimidinone-l-p-D-(2 -deoxyriboside) (d).

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