2.3- Unsaturated C-nucleoside

Reference is made in Chapter 3 to the synthesis of C-glycosides from glycal derivatives by use of palladium adducts, and related work leading to 2,3-unsaturated C-nucleosides is reported in Chapter 20. 

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... 

In addition to the previously mentioned spiro 1,3-oxazine C-nucleoside derivative 699 (85CPB102) (Section XIV, A Scheme 187), the unsaturated l,3-oxazin-2-yl C-nucleoside 1037 was prepared from the 5-benzyl )8-d-ribofuranosylthioformimidate derivative 1036 by reaction with diketene (85CPB102) (Scheme 300). 

Full details of previously reported work (Vol. 26, p. 242, ref 159 and Vol. 25, p. 173, ret 43) on the photocatalysed addition (by C-C bonding) of alcohols to 2,3-unsaturated 1,4-lactones as intermediates for branched-chain nucleosides has appeared. ... 

DMF. The acid-catalysed reaction of 3,4,6-tri-O-acetyl-D-glucal with benzo-triazole or 6-methylthiopurine in acetonitrile at ca. 90 °C afforded a mixture of the corresponding T,2 -unsaturated isonucleosides and 2, 3 -unsaturated nucleosides in which the former [e.g, (594)] predominated. " T.l.c. showed that the... 

A number of -acyl- and thioureido-derivatives of 3 -amino-3 -deoxythymidine have been prepared. 1 0 Michael addition of phthalimide to enal (81) was used in the synthesis of the 3 -amino-2 ,3 -dideoxyhexo-furanose nucleosides (82) (all four isomers, R=H, Me, halogen),191 and a similar enal prepared by mercuric-ion catalysed hydrolysis of L-rhamnal was used in the same way to make the L-acosaminyl nucleoside (83) and its -anomer, and the L-ristosaminyl systems (epimers at C-3 ). 2 Michael addition of 1,2,4-triazole to (81) led, after base-sugar condensation, to the triazolyl-substituted nucleosides (84, B=T, U), together with the analogous hexopyranose systems. 93 xhe imidazolyl nucleosides (85) can be made by reaction of 3 -amino-3 -deoxythymidine with l,4-dinitroimidazoles, 9 whilst the unsaturated imidazole nucleoside (87) was made by treating the phenylselenone (86) (see Section 6) with imidazole. 195... 

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). 

Formycin and formycin B with modified sugar subunits have also been prepared using, mostly, the nucleoside-nucleoside approach. In one instance, however, 2 -deoxyformycin B (458) was prepared by regio- and stereospecific palladium-mediated C—C bond formation between the fu-ranoid glycal 454 and protected 3-iodopyrazolo[4,3-d]pyrimidine. The C-nucleoside 455 having an unsaturated sugar moiety was subsequently elaborated to 458 (92JOC4690) (Scheme 125). 

The 1,2-disubstituted azirine acyclo C-nucleosides 36 were synthesized by cyclization of the a-bromo-a ,/3-unsaturated esters 35 with primary amines (671ZV2691) (Scheme 4),... 

Condensation of syn- or anti-27 with hydrazine afforded new pyrazole derivatives 28 with a stereodefined and protected amino diol side chain [64]. The preparation of push-pull substituted unsaturated monosaccharide derivatives and their use in the synthesis of nucleoside analogs have been reviewed [65]. Thus, the 2-formyl pentose glycals were transformed to the corresponding acyclo-C-nucleosides 29 [66]. Similarly, the benzy-lated 2-formylglycals reacted with hydrazine derivatives to afford the substituted l,2,4-tri-0-benzyl-lC-(lH-pyrazol-4-yl)-D-tetritols the deprotection of which was achieved with Pd/H2 to yield the lC-( 1-methyl-lH-pyrazol-4-yl)-D-tetritols [67]. 3-0-Benzyl-6-deoxy-l,2-0-isopropylidene-o -D-xylo-hept-5-ulofuranurono-nitrile was reacted with f, N-dimethylformamide dimethyl-acetal in THF to furnish the (E)-3-0-benzyl-6-deoxy-6-dimethyl-aminometh-ylene-l,2-0-isopropylidene-Q -D-xylo-hept-5-ulofuranurono-nitrile as a major product, and on treatment with carbon disulfide and methyl iodide under basic conditions afforded 3-0-benzyl-6-deoxy-l,2-0-isopropylidene-6-[bis(methylsulfanyl)methylene]-a-D-xylo-hept-5-ulofuranurono-nitrile. Further reaction with hydrazines yielded the reversed pyrazole-C-nucleoside analogs [68]. 

Addition reactions to unsaturated C-glycosides have continued to be utilized to synthesize C-nucleosides. Thus 2,3,5-tri-0-benzoyl-/3-D-ribofuranosyl cyanide with sodium azide-ammonium chloride in DMF gave the tetrazole (72) in 72% yield. Treatment of (72) with acetic anhydride gave the 1,3,4-oxadiazole nucleoside (73). The benzothiazole (74) was obtained from the ribosyl cyanide by reaction with 2-aminothiophenol. Analogous compounds were derived from jS-D-ribo-, 8-D-xylo-, and j3-D-galactopyranosyl cyanides. A similar reaction has been used by a different group to synthesize a-D-arabinosyl tetrazole (75). Reaction of 3,4-di-0-benzoyl-2,5-anhydro-D-... 

HMPT at room temperature to give the 3, 4 -unsaturated nucleoside. Details of the formation of saccharinic acid nucleosides from 2, 3 -diketo-nucleosides have appeared (c/. Vol. 8, p. 151). 

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