Spirocyclic nucleosides

S. Tripathi, B. G. Roy, M. G. B. Drew, B. Achari, and S. B. Mandal, Synthesis of oxepane ring containing monocyclic, conformationally restricted bicyclic and spirocyclic nucleosides from D-glucose A cycloaddition approach, J. Org. Chem., 72 (2007) 7427-7430. 

S. Z. Dong and L. A. Paquette, Stereoselective synthesis of conformationally constrained 2 -deoxy-4 -thia beta-anomeric spirocyclic nucleosides featuring either hydroxyl configuration at C5, J. Org. Chem., 70 (2005) 1580-1596. 

The discovery of spirocyclic nucleosides with anti-HIV-1 activity has prompted Chattopadhyaya and co-workers (54,55) to prepare spiroisoxazolidine nucleosides (Scheme 1.6). Thus, after proving the reactivity of related systems in an... 

Conformationally constrained 2 -deoxy-4-thia /3-anomeric spirocyclic nucleosides have been synthesized by Dong and Paquette <2005JOC1580>. Osmium-catalyzed dihydroxylation of the spirocyclic dihydrothiophene 135 in the presence of DABCO gave the air-diol 136 in 53% yield which was protected as an acetonide hydrolysis using LiOH in aqueous THE and subsequent Meerwein-Ponndorf-Verley reduction of the keto compound 137 gave a diaster-eomeric mixture of alcohols (Scheme 36). 

Reductive removal of the PhSe group from 140 followed by deprotection of hydroxyl groups afforded the spirocyclic nucleoside (Scheme 37). Several analogs have been prepared by following the above synthetic protocol using different nucleobases. 

Spirocyclic nucleosides in medicinal chemistry 12MRM1485. Squaraine dyes in photodynamic therapy From basic design to in vivo demonstration 120BC911. 

The spirocyclic nucleoside 105 has been made fay cyclization of a cyanomesylate similar chemistry carried out at C-3 has been mentkNied in previous Vcdumes, and see also ie. 147 and 148 below. 

Nucleosides based upon monocyclic, fused and spirocyclic oxepines have been synthesised via nitrone cycloaddition reactions <07JOC7427>, while oxepine nucleic acids were synthesised from the ring expansion of cyclopropanated glycals <07JACS8259>. 

The acetylenic nucleosides 130 (B=normal bases, 5-F-Ura, 5-F-Cyt) have been prepared by stereoselective addition of lithium Tms-acetylide to 129, followed by nucleoside formation. The Ura and Cyt compounds had particular antitumour activity. The allofuranosyl analogue 131 of TSAO-T has been prepared, " and 3 -ketonucleosides were treated with JV-methylhydroxylamine, followed by reaction of the nitrones with lithioethyl acetate, to give the spirocyclic compounds 132, also related to TSAO-T. Some other compounds with branches at C-3, prepared in connection with making antisense oligonucleotides, are mentioned in Section 12. 

Gurjar and co-workers prepared several novel carbohydrate-based spirocycles and a spirocyclic proline derivative for applications in peptide, nucleoside, and carbohydrate synthesis. Ring-closing metathesis of carbohydrate diene precursor 78 furnished the corresponding spirocycle 80 in 88% yield using a catalytic amount of 3 in dichloromethane. Reaction of proline derivative 79 under similar conditions gave the corresponding spirocyclic peptide 81 in 96% yield. 

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