When nucleoside chemistry met hypervalent iodine reagents.

Antigoni Kotali,Barbara Zajc,Mahesh K. Lakshman

doi:10.24820/ark.5550190.p010.281

Abstract

There has been increasing use of hypervalent iodine reagents in the field of nucleoside chemistry. Applications span: (a) synthesis of nucleoside analogues with sulfur and seleno sugar surrogates, (b) synthesis of unusual carbocyclic and ether ring-containing nucleosides, (c) introduction of sulfur and selenium into pyrimidine bases of nucleosides and analogues, (d) synthesis of isoxazole and isoxazoline ring-containing nucleoside analogues, (e) involvement of purine ring nitrogen atoms for remote C-H bond oxidation, and (f) metal-catalyzed and uncatalyzed synthesis of benzimidazolyl purine nucleoside analogues by intramolecular C-N bond formation. This review offers a perspective on developments involving the use of hypervalent iodine reagents in the field of nucleoside chemistry that have appeared in the literature in the 2003-2017 time frame.

Highlights

We describe some of the applications of hypervalent iodine reagents to the field of nucleoside modification
In 2003, the use of hypervalent iodine reagents was demonstrated for the synthesis of pyrimidine nucleoside analogues containing a sulfur atom in the sugar-like portion.[20]
We have summarized some very interesting and unique reactions promoted by hypervalent iodine reagents

Summary

Glycosylation-Type Reactions Leading to Nucleoside Analogues

In 2003, the use of hypervalent iodine reagents was demonstrated for the synthesis of pyrimidine nucleoside analogues containing a sulfur atom in the sugar-like portion.[20]. Synthesis of the seleno analogues of purine nucleosides have been reported.[24] Initially, the authors attempted syntheses with the selenosaccharide analogue 35 This derivative was not useable; with 6-chloropurine the N7 “glycosylation” product was obtained with a hypervalent iodine reagent, but this could not be isomerized to the N9 isomer. An interesting approach was undertaken for access to C-nucleoside analogues.[26] Cyclopentadiene and cyclohexadiene were subjected to hydrosilylation followed by conversion to the triethoxy and trimethyl silanes (Scheme 11) These compounds were investigated for their reactions with bis(trimethylsilyl)uracil, promoted by TMSOTf and a hypervalent iodine reagent (IOB, PIDA, PIFA, and HTIB, see Scheme 11). A proposed mechanism is shown in Scheme 14, where an initial addition product from dihydropyran undergoes reaction with bis(trimethylsilyl)uracil (either directly or via an oxocarbenium ion), followed by an elimination to yield 55. Separation of the uracil nucleoside analogues and conversion to the cytosine derivatives

Miscellaneous Hypervalent Iodine Reagent Mediated Nucleoside Modifications

Purinyl N-Directed C–H Bond Oxidation Using PIDA

Metal-Free Intramolecular C–N Bond Formation in Purine Nucleosides Using PIDA

Conclusions

Findings

Antiviral Nucleosides