1 - cytosine stereochemistry

All of the direct fluorinations reported appear to be addition-elimination processes with solvent involvement (Scheme 42). A study of the mechanism and stereochemistry of uracil and cytosine fluorination using fluorine and acetyl hypofluorite has implicated a radical-cation mechanism (86JOC1466). The effect of acetate ion on the products proved to be important. In its absence both m-isomers (49) and trans-isomers (50) were observed in the reaction mixture, but only 50 [and 5-fluorouracil (51)] in its presence. The process has been rationalized in terms of the reaction diagram shown in Scheme 43. NMR studies have revealed that the acetate from the solution containing acetate ion, rather than the residue from acetyl hypofluorite, binds to the 6-position of uracil to form the intermediates (49 and 50). Acetate is a sufficiently strong base to induce trans-elimination of acetic acid from the cis-isomer (49). 5-Fluorouracil (51) was obtained in 45% yield from these reaction sequences (86CJC424). 

Vinylphosphonates of cytosine, uracil and ara-C have been prepared by Wittig reactions, and intermediates in these syntheses were hydroxylated using AD-mix-a to give the product 196 and the related derivatives of uridine and cytosine, Geminal hydroxyphosphonates 197 (R = Me or H, and with all four nucleobases) have been prepared by addition of dimethyl phosphite or tris-Tms phosphite to 5 -aldehydes. Similar products were obtained from 2, 3 -0-iso-propylidene ribonucleosides, except in the case of adenosine. NMR studies indicated that the major diastereoisomer formed in each case had 5 -R-stereochemistry, and in some cases this was produced in up to 90% d.e. ... 

SPG complex. In Model Dl, every glucose residue in the main chain interacts with the cytosine in a DNA-like double helix. Since the distance between the neighboring C-2 carbon s OH is about 4 A and the stacking distance between cytosine moieties is 3.0—3.6 A, this model is reasonable from the stereochemistry. However, the stoichiometric number n = 0.25) does not agree with the experi-... 

Robins MJ, MacCoss M, Naik SR, Ramani G (1976) Nucleic acid related compounds. 21. Direct fluorination of uracil and cytosine bases and nucleosides using trifluoromethyl hypofluorite. Mechanism, stereochemistry, and synthetic applications. J Am Chem Soc 98 7381-7389... 

Visser GWM, Boele S, Van Halteren BW, Knops GHJN, Herscheid JDM, Brinkman GA, Hoekstra A (1986) Mechanism and stereochemistry of the fluorination of uracil and cytosine using fluorine and acetyl hypofluorite. J Org Chem 51 1466-1471... 

A novel method for the stereocontrolled synthesis of a-ribonucleosides, using either of two pyridine-containing leaving groups, is outlined in Scheme 2. The method was also applied to the synthesis of l-(P-D-arabinofuranosyl)cytosine (also with 1,2-cu-stereochemistry), and the authors discuss the reasons for the selectivity in terms of remote activation . ... 

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