4 ,5 -Unsaturated nucleoside

O-isopropylidene derivative (57) must exist in pyridine solution in a conformation which favors anhydro-ring formation rather than elimination. Considerable degradation occurred when the 5-iodo derivative (63) was treated with silver fluoride in pyridine (36). The products, which were isolated in small yield, were identified as thymine and l-[2-(5-methylfuryl)]-thymine (65). This same compound (65) was formed in high yield when the 5 -mesylate 64 was treated with potassium tert-hx Xy -ate in dimethyl sulfoxide (16). The formation of 65 from 63 or 64 clearly involves the rearrangement of an intermediate 2, 4 -diene. In a different approach to the problem of introducing terminal unsaturation into pento-furanoid nucleosides, Robins and co-workers (32,37) have employed mild base catalyzed E2 elimination reactions. Thus, treatment of the 5 -tosylate (59) with potassium tert-butylate in tert-butyl alcohol afforded a high yield of the 4 -ene (60) (37). This reaction may proceed via the 2,5 ... 

The high chemoselectivity for the Baeyer-Villiger process was utilized in the synthetic elaboration of another hetero-bicyclic substrate. The biooxidation only provides the expected unsaturated lactone in a desymmetrization reaction without compromising the olefin functionality. The biotransformation product was then converted to pivotal intermediates for C-nucleosides like showdomycin, tetrahydro-furan natural products like kumausyne, and goniofufurone analogs in subsequent chemical operations (Scheme 9.17) [161]. 

This reaction, using sodium naphthalenide, has been used to prepare unsaturated nucleosides. 

D-Ribonolactone is a convenient source of chiral cyclopentenones, acyclic structures, and oxacyclic systems, useful intermediates for the synthesis of biologically important molecules. Cyclopentenones derived from ribono-lactone have been employed for the synthesis of prostanoids and carbocyclic nucleosides. The cyclopentenone 280 was synthesized (265) from 2,3-0-cyclohexylidene-D-ribono-1,4-lactone (16b) by a threestep synthesis that involves successive periodate oxidation, glycosylation of the lactol with 2-propanol to give 279, and treatment of 279 with lithium dimethyl methyl-phosphonate. The enantiomer of 280 was prepared from D-mannose by converting it to the corresponding lactone, which was selectively protected at HO-2, HO-3 by acetalization. Likewise, the isopropylidene derivative 282 was obtained (266) via the intermediate unsaturated lactone 281, prepared from 16a. Reduction of 281 with di-tert-butoxy lithium aluminum hydride, followed by mesylation, gave 282. 

Unsaturated monosaccharides [e.g. (91)] react with the Ph3P-DAD combination in the presence of phthalimide, with inversion of configuration of C-4, to form the phthalimido-derivatives (92).82 Treatment of carbohydrates having a free anomeric OH group with 6-chloropurine, DAD, and methyldiphenylphosphine gives the purine nucleosides (93).83... 

Unsaturated nucleosides with fluorine atoms on the 2 or 3 position have also been investigated for their potential antiviral properties (HIV and HBV). 

Stanovnik and co-workers (100,101) systematically investigated the cycloaddition reactions of diazoalkanes with unsaturated nitrogen heterocycles, such as azolo-[l,5-fl]pyridines, pyridazin-3(2/7)-ones, and [fo]-fused azolo- and azinopyridazines. The Stanovnik group have studied the further transformations of the products and reviews of this chemistry are available. In a typical example, the reaction of 6-chlorotetrazolo[l,5-/7]pyridazine (37) with 2-diazopropane yields the NH,NH-dihy-dro-pyrazolo[4,3-(i]tetrazolo[l,5-/7]pyridazine 38 (102) (Scheme 8.11). The latter substrate reacts with acetone to produce an azomethine imine 39 that thermally rearranges to give the fused dihydro-1,2-diazepine 40. The azomethine imine obtained with glucose can be trapped with methyl acrylate to furnish the C-nucleoside 41 (103). 

Comparatively little was previously known about photoaddition reactions to unsaturated substrates of different structure. Elements of water add to the A5 6 in the pyrimidine ring of 1,3-dimethyluracil (CXXXYII)301 and probably of nucleosides and nucleotides of cytosine261,307 upon irradiation with ultraviolet light to give products such as CXXXVIII. CXXXVIII reverts to CXXXVII under the influence of acid, alkali, or heat. 

The syntheses of both l-(3-deoxy-/ -D-g/i/cm>-pentofuranosyl-2-ulose)uracil (25c) and l-(3-deoxy-/ -D-g/ /cm>-pentofuranosyl-2-ulose)cytosine (30b) by selective elimination reactions have been reported.4,5 Thus, the reaction of sulfonyl derivatives of the cytosine nucleoside 26, and uracil nucleosides 23a, 23c, and 28, with sodium benzoate in N,N-dimethylformamide (DMF) leads to 3 -deoxy-2 -ke-tonucleosides by way of such (presumed) unsaturated intermediates as 24a, 24c, 29a, and 29b. However, in one instance, the intermediate... 

This Subsection deals with the preparation of 2 - and 4 -ketohexosyl-purines and -pyrimidines, which have proved to be versatile synthetic intermediates. A 5 -keto derivative of a hexofuranose nucleoside is also described. The synthesis of epoxy-, halogeno-, unsaturated, epimino-, and thio-ketonucleosides will be developed in subsequent Subsections and Sections. 

Treatment of the unsaturated C-nucleoside 69 with activated manganese dioxide afforded 2-(l,5-anhydro-2,6-dideoxy-L-m/thro-hex-l-eni-tol-l-yl-3-ulose)-8-nitro-u-triazolo[l,5-fl]pyridine (70) in 40% yield.13... 

Among the unsaturated ketonucleosides may be classified the disaccharide derivative 74, which is an analog of the biologically active compound 68c. The key intermediate for the synthesis of this unsaturated ketodisaccharide nucleoside was the partially protected, disaccharide nucleoside 73, which was prepared by two separate routes,56 Treatment of 73 with the Me2SO-acetic anhydride reagent for two days at room temperature afforded 7-[2,3-di-0-benzoyl-4-0-(3-0-benzoyl-2,6-di-deoxy - / - d - glycero - hex - 2 - enopyranosyl - 4 - ulose) - 6 - deoxy - / - d -glycopyranosyl]theophylline (74), isolated crystalline.56... 

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