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

Abstract

Treatment of the protected (E)-5′-deoxy-5′- [(p-toluenesulfonyl)methylene]uridine and adenosine derivatives with tributyl-or triphenylgermane hydride (AIBN/toluene/Δ) effected radical-mediated germyldesulfonylations to give 5′-(tributyl-or triphenylgermyl)methylene-5′-deoxyuridine and adenosine derivatives as single (E)-isomers. Analogous treatment of 2′-deoxy-2′-[(phenylsulfonyl) methylene]uridine with Ph 3 GeH afforded the corresponding vinyl triphenylgermane product. Stereoselective halodegermylation of the (E)-5′-(tributylgermyl)methylene-5′-deoxy nucleosides with N-iodosuccinimide or N-bromosuccinimide provided the Wittig-type (E)-5′-deoxy-5′-(halomethylene) nucleosides quantitatively, while no halodegermylations was observed with the 5′-deoxy-5′-(triphenylgermyl)methylene counterparts. Treatment of the vinyl trialkylgermanes with aqueous trifluoroacetic acid effected protiodegermylation, while vinyl triarylgermanes were stable under the acidic conditions.

Hydrogermylation of 5-Ethynyluracil Nucleosides: Formation of 5-(2-Germylvinyl)uracil and 5-(2-Germylacetyl)uracil Nucleosides

“…Hydrogermylation of 1 with Ph 3 GeH in the presence of B(C 6 F 5 ) 3 22 in CH 2 Cl 2 at ambient temperature produced 2a in lower than 10% yields (TLC, 1 H NMR) while prolonged heating (48 h, reflux) produced a complex reaction mixture. The Pd(PPh 3 ) 4 -catalyzed hydrogermylation 19 8b (71%), confirming stability 28 of the C(sp 2 )-Ge(alkyl) 3 bond in basic conditions. Hydrogermylation of the toluoyl protected 5-ethynyl-2′deoxyuridine 6 with Ph 3 GeH/Et 3 B produced the vinyltriphenylgermane Z-9a (61%) along with the 5-[2-(triphenylgermyl)acetyl] product 12a (12%, entry 10).…”

“…Analogous hydrogermylation of 5 with Me 3 GeH/Et 3 B at ambient temperature yielded only vinyl trimethylgermane 7b ( E / Z, 45:55; entry 9). Deprotection of E / Z - 7b with MeONa/MeOH afforded uridine analogue E / Z - 8b (71%), confirming stability of the C(sp 2 )-Ge(alkyl) 3 bond in basic conditions.…”

“…Treatment of E/Z- 9b (40:60) with N -bromosuccinimide (NBS) followed by deprotection (NH 3 /MeOH) afforded a mixture of 5-(2-bromovinyl)-2′-deoxyuridines ( E/Z , ∼2:3; 70%) illustrating a potential application of vinyl 5-[2-(trimethylgermyl)vinyl]uracil nucleosides toward the synthesis of 5-(2-halovinyl) analogues with possible applications for radiolabeling. Stereoselective halodegermylation of vinyl trialkylgermanes with NBS or NIS with retention of the double-bond geometry is known. ,, It is also worth mentioning that substitution of the trialkylgermyl group on an sp 2 carbon , (as well as sp carbon , ) with a halogen proceed not only more easily than the substitution of the corresponding trialkylsilyl group but also with improved stereochemical outcome.…”

“…Stereoselective halodegermylation of vinyl trialkylgermanes with NBS or NIS with retention of the double-bond geometry is known. 22,28,29 It is also worth mentioning that substitution of the trialkylgermyl group on an sp 2 carbon 29,30 (as well as sp carbon 30,31 ) with a halogen proceed not only more easily than the substitution of the corresponding trialkylsilyl group but also with improved stereochemical outcome.…”

Developing of Germyldesulonylation and Thiodesulfonylation Reactions for the Synthesis of Novel Nucleoside Analogues. Efficient Synthesis of Novel (α-Fluoro)vinyl Sulfides

“…I also developed the germyldesulfonylation reaction for the removal of the vinyl sulfonyl group located on C2' of the nucleosides in Wnuk laboratory. 119 3.3.…”