VORBRUGGEN Nucleoside synthesis

VORBRUGGEN Nucleoside synthesis Synthesis of nucleosides by condensation of sugars with silyl heteiocycies and Lewis acids such as SnCU or trimethylsilyf Inflate 3. 

H. VoRBRUGGEN, C. RuH-PoHLENZ, Organic Reactions, Vol 55, 2000, Wiley, New York [59a] H. VoRBRUGGEN, C. Ruh-Pohlenz, Handbook of Nucleoside Synthesis, ). Wiley ... 

For further Pummerer reactions with silylated heterocyclic bases see Refs. 414a—414i in Handbook of Nucleoside Synthesis , H. Vorbruggen, C. Ruh-Pohlenz, Wiley-Inter-science. New York, 2001... 

Isoxazolidinyl nucleosides were also obtained through a less direct approach based on 1,3-dipolar cycloaddition of nitrones with vinyl acetate, followed by coupling of the isoxazolidin-5-yl acetates with silylated nucleobases (Vorbruggen nucleosidation) (Scheme 145, method B) <2003TA2717>. In the synthesis of 589, the first approach (method A) was more stereoselective whereas method B gave better yields. 

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. 

Nucleoside chemistry is traditionally labor intensive and the output of compoxmds is consequently relatively low. In order to overcome these limitations, several groups have implemented a parallel or combinatorial approach to speed up the synthesis process this chapter will only discuss the use of solid support for the synthesis of nucleoside libraries, not for the piupose of oligonucleotide synthesis. Chang <05BMC4760> attached a purine diehloride to a Merrifield 3,4-dihydropyran resin, followed by sequential displacement of the two ehloro atoms by various amines. The purine heterocyclic bases were then condensed with Dd.-ribofuranosides following a classical Vorbruggen method to yield nucleosides of general formula 171. 

Two new nucleosides of cyclic sulphamides (392 and 393) have been reported by Vorbruggen and co workers374. The synthesis involves reaction (equation 128) of the 1,2,6-thiadiazine-1,1-dioxide (394) with l-0-acetyl-2,3,5-tri-0-benzoyl-/ -D-ribofuranose (395) the intermediate nucleoside (396) is debenzylated to give 3-amino-6-(2,3,5-tri-0-benzoyl-/ -D-ribofuranosyl)-6//-1,2,6-thiadiazine-1,1 -dioxide (392). 3,6-Dihydro-3 -oxo-6-(/ -D-ribofuranosyl)-2//-1,2,6-thiadiazine-1,1 -dioxide (393) is prepared in a similar manner. 

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