Nucleic acid related compounds. 78. Stereocontrolled syntheses of 6′(E and Z)-halovinyl analogues from uridine-derived vinylsulfones via vinyltin intermediates

Abstract

Treatment of the 6′(E)-tosylvinyl homonucleoside 1a with Bu3SnH/AIBN/toluene/Δ gave separable mixtures of 6′-vinylstannanes 2a(E/Z) in high yields. Stereospecific halodestannylations with N-iodosuccinimide, bromine, and N-bromosuccinimide proceeded smoothly to give the 6′(E or Z)-iodo(and bromo) vinyl compounds with retention of configuration. Chlorine or iodobenzene dichloride effected moderately stereoselective chlorodestannylation. Treatment of 2a with NH4F/MeOH/Δ resulted in carbon–tin bond cleavage to give the free vinyl derivative 4a. Aqueous trifluoroacetic acid effected concomitant protiodestannylation and deprotection of 2a to give 4b. Treatment of 2a(E) with lead tetraacetate/acetonitrile and deprotection afforded acetylenic derivative 3b.

Application of Germyldesulfonylation Reactions to the Synthesis of Germanium-Containing Nucleoside Analogues

“…Thus, both purine and pyrimidine nucleosides underwent desulfonylation with either trialkyl- or triarylgermanes. The yields were higher for the uridine substrates as was also observed in the case of the stannyldesulfonylation reactions 3,6. It is noteworthy that contrary to the stannyldesulfonylation reactions,3,6 the germyldesulfonylations of the vinyl sulfones derived from the sugar modified nucleosides are stereoselective since the corresponding ( Z )-isomers of vinyl germanes 7 or 8 were not isolated from the crude reaction mixtures.…”

“…The yields were higher for the uridine substrates as was also observed in the case of the stannyldesulfonylation reactions 3,6. It is noteworthy that contrary to the stannyldesulfonylation reactions,3,6 the germyldesulfonylations of the vinyl sulfones derived from the sugar modified nucleosides are stereoselective since the corresponding ( Z )-isomers of vinyl germanes 7 or 8 were not isolated from the crude reaction mixtures. Germyldesulfonylation reactions presumably occurred via the radical addition-elimination mechanism in analogy to the silyl- and stannyldesulfonylation processes 1,18,26…”

“…Adenosine-derived sulfone 6 also underwent germyldesulfonylation reaction with Bu 3 GeH to afford the vinyl germane ( E ) - 8a (46%). The analogous stannyldesulfonylation of 5 and 6 with Bu 3 SnH afforded the corresponding ( E/Z ) - 5′-(tributylstannyl)methylene-5′-deoxyuridine6 and adenosine3 derivatives in 87% and 61% yields, respectively. Treatment of 5 and 6 with triphenylgermane hydride gave ( E )-5′-deoxy-5′-(triphenylgermyl)methylene nucleosides 7b (72%) and 8b (42%), respectively.…”

“…1,2 Stannyldesulfonylation of the vinyl sulfone 2a followed by halodestannylation of the resulting vinyl stannanes 2b was a key step in the synthesis of 5′-deoxy-5′-(halomethylene)adenosines 2c , which were found to be potent inhibitors of S- adenosyl-L-homocysteine (AdoHcy) hydrolase and valuable probes to study hydrolytic activity of the enzyme 3–5. Stannyldesulfonylation/protiodestannylation of the (α-fluoro)vinyl sulfones and stannyldesulfonylation/halodestannylation of the vinyl sulfones procedures allowed synthesis of the various 5′-deoxy-5′-(halomethylene)nucleoside analogues derived from uridine,6 L-adenosine,7 3′-deoxyadenosine,8 and 6- N- cyclopropyladenosine9 as well as 5′-deoxy-5′-(halomethylene)ribose derivatives,10 among others 11. The vinyl sulfone precursors have been conveniently prepared by treatment of the nucleoside 2′-keto or 5′-aldehyde derivatives with the sulfonyl-stabilized Wittig reagents,1,12,13 and chemistry of the vinyl-sulfone modified carbohydrates and nucleosides has been reviewed 14.…”

Synthesis of 5′-functionalized nucleosides: S-Adenosylhomocysteine analogues with the carbon-5′ and sulfur atoms replaced by a vinyl or halovinyl unit

“…Merck kieselgel 60 (230-400 mesh) was used for column chromatography. HPLC purifications were performed using XTerra® preparative RP 18 OBD™ column (5µm 19 × 150 mm) with gradient program using CH 3 CN/H 2 O as a mobile phase. Elemental analyses were determined by Galbraith Laboratories, Knoxville, TN.…”