Anhydro-nucleosides

Pteridine, 2-amino-4,6,7-trimethyl-basicity, 3, 267 Pteridine, 2,2 -anhydro-nucleosides, structure, 3, 283 Pteridine, 2,5 -anhydro-nucleosides structure, 3, 283 Pteridine, 6-aryl-synthesis, 3, 316 Pteridine, 7-aryl-synthesis, 3, 314... 

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 ... 

Removal of the 2 -sulfonyloxy group of 859 in a basic medium, followed by reaction with metal halides (LiBr and Nal) or hydrogen halides (HCl-1,4-dioxane, HBr-acetone, or0.1% HFin l,4-dioxane-AlF3)gave, byway of the 2,2 -anhydro intermediate 861, the 2 -halo derivatives 862-865. The 2 -deoxy analog 866 and l-(6-deoxy-6-fluoro- ff-D-mannopyranosyl)thy-mine were also prepared from 864 (R = H) and 861 (R = H), respectively. l-(4-Deoxy-4-fluoro-y -D-glucopyranosyl)thymine was obtained by the condensation method. A different kind of nucleoside, 5-(5-deoxy-5-fluoro-2,3-0-isopropylidene-a-D-ribofuranosyl)-l,3-dimethyluracil has also been prepared. ... 

C-Nucleoside analogue 464 of this ring system was prepared (86SC35) from 2,5-anhydro-3,4,6-tri-0-benzoyl-L-mannose dimethyl acetal 462 and 6-(2-aminophenyl)-3-methylthiotriazin-5(2//)-one 463 in the presence of acetic and hydrochloric acids. 

In contrast to other 2,5-anhydroaldoses (which exhibit mutarota-tion, possibly due to the formation of hemiacetals28), 2,5-anhydro-D-glucose does not show any mutarotation.27 The importance of this compound as a potentially useful precursor to C-nucleosides warrants a reinvestigation of the deamination reaction, and the definitive proof of the structure of the compound. The readily accessible 2,5-anhydro-D-mannose (11) does not possess the cis-disposed side-chains at C-2 and C-5 that would be required of a synthetic precursor to the naturally occurring C-nucleosides, with the exception of a-pyrazomycin (8). The possibility of an inversion of the orientation of the aldehyde group in 11 by equilibration under basic conditions could be considered. 

The potentialities of this method are such that, with the proper choice of hexofuranose derivative, access can be gained to 2,5-anhydroaldoses in which the side chains have the cis orientation, as would be required for further elaboration into C-nucleosides. Matsui and coworkers62 reported the synthesis of modified C-nucleosides by acidic treatment of 3-0-benzyl-l,2-0-isopropylidene-5,6-di-0-(methylsulfonyl)-/3-L-talofuranose (60), to give 2,5-anhydro-3-0-benzyl-6-0-(methylsulfonyl)-aidehydo-D-allose dimethyl acetal (61). 

Intramolecular displacement of primary sulfonyloxy or halide groups in derivatives of D-mannitol can also be brought about under basic conditions, albeit in low yield. Treatment of l,6-di-0-(methyl-sulfonyl)-D-mannitol (78), or the corresponding dichloride derivative, with sodium methoxide gave 2,5 3,6-dianhydro-D-glucitol74 (79). Treatment of the latter with hydrochloric acid at 100° in a sealed tube gave the 6-chloro-6-deoxy derivative (80), which was converted into the known 2,5-anhydro-l,6-di-0-benzoyl-D-glucitol45 47 (32). The sequence 78-80 is of interest in the context of C-/3-D-nucleoside precursors, but it suffers from the fact that yields are low. 

The Wittig reaction, or its phosphonate modification, can be a very useful reaction in the synthesis of anomerically functionalized precursors to C-nucleosides, particularly when the ring-closure reaction leads to five-membered, anhydro derivatives, and occurs with a high degree of stereocontrol. Zhdanov and coworkers,130 showed that the following five-membered, Wittig products (179-182) were formed from various free sugars and (p-methoxybenzoyl)- and (acetyl-methylene)-triphenylphosphoranes. 

Other sulfide photoreactions result when appropriate nucleoside derivatives are photolyzed. Upon irradiation in acetonitrile, 9-[5-deoxy-2,3-0-isopropylidene-5-(phenylthio)-/3-D-ribofuranosyl]-adenine (53) is converted into the anhydronucleoside 8,5 -anhydro-(5 -deoxy-2, 3 -0-isopropylidene-adenosine) (55) in 66% yield.111 Similar reactions were observed when other sulfur-containing nucleosides were irradiated (see Table XIII). The reaction of the sulfide 53... 

By opening an oxirane or by displacement of cyclic sulfate or of an anhydro-nucleoside by fluoride ions (KHF2). 

Despite the fact that secondary hydroxyl groups of nucleosides also react with 23 (see later), selective iodination of only the primary hydroxyl group in some unprotected, pyrimidine nucleosides can also be achieved.82 Thus, brief treatment of thymidine with 1.1 mol-equivalents of 23 in N,N-dimethylformamide gave crystalline 5 -deoxy-5 -iodothymidine in 63% yield. It was even possible to effect some selective iodination of the 5 -hydroxyl group of 2,2 -anhydrouri-dine without excessive cleavage of the (quite labile) anhydro linkage. 

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... 

Dimroth rearrangement has taken place in the C-nucleoside series, whereby the reaction of ethyl 2,5-anhydro-6-0-benzoyl-D-allonodithioate (322) with 2-hydrazinopyrimidine did not afford the 3-substituted... 

Another example of based-catalyzed elimination in the 2-deoxy sugar series is that of l-[2-deoxy-3-0-(methylsulfonyl)-5-0-trityl-/3-D-eryMro-pentofuranosyl]uracil and 2, 3-anhydro-l-(2-deoxy-5- 0-trityl-/3-D-<. reo-pentofuranosyl) uracil, which, when treated with potassium ferf-butoxide in methyl sulfoxide, give a 70% yield of a 2,3-unsaturated nucleoside.28... 

K. Chow and S. Danishefsky, Stereospecific Vorbruggen-like reactions of 1,2-anhydro sugars. An alternative route to the synthesis of nucleosides, J. Org. Chem., 55 (1990) 4211-4214. 

T. Ogawa, M. Matsui, H. Ohrui, H. Kuzuhara, and S. Emoto, Synthetic studies on C-nucleosides. 6. Synthesis of 2,5-anhydro-3,4,6-tri-0-benzyl-L-talose dimethyl acetal via... 

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