An Efficient Method for the Synthesis of β-d-Ribonucleosides Catalyzed by Metal Iodides

Abstract

Several p-D-ribonucleosides were synthesized in high yields under mild conditions by N-glycosylations of methyl 2,3,5-tri-O-benzoyl-~-D-ribofuranosylcarbonate (1) with trimethylsilylated nucleoside bases in acetonitrile using a catalytic amount of metal iodide such as SnI2, SbI3 or Te14. A deprotection of N6-benzoyl group of coupling product took place to a considerable extent when N6-benzoyl-N6@-bis(trimethylsily1)adenine was employed as a nucleoside base using Sn12 or SnClz as a catalyst while it was minimized when SbI3 or TeI4 was used. Further, the Nglycosylation of 1 with 7-trimethylsilyltheophylline in the presence of a catalytic amount of metal iodide was more effectively achieved in nitrile solvents other than acetonitrile.The chemistry and biochemistry of nucleic acids are getting more and more important because nucleic acids play significant roles on the determination of nature and function of organisms, on the reproduction for conservation of species and on the control of biological processes such as metabolisms and biosyntheses. Nucleosides which are the components of nucleic acids also have many essential functions such as regulating enzyme and cell activities and having physiological control of blood pressure.l Therefore, analogs of nucleosides are used as therapeutic agents such as antitumor (araC) and antiviral agents (e.g., ACV, araA, AZT and ddI), and even more # This paper is dedicated to Dr. Yoshihisa Mizuno on the occasion of his 75th birthday. 17

A One-Pot Synthesis of D-Ribonucleosides Using Natural Phosphate Doped with KI in HMDS

“…The same author has reported new conditions for Nglycosylations using a catalytic amount of a metal iodide such as SnI 2 , SbI 3 , or TeI 4 [3]. A method for the preparation of acyclonucleosides was reported by Ubasawa et al using HMDS/TMSCl/KI (or NaI) as the reagent [4].…”

“…There are several known methods for the synthesis of ribonucleosides. The reactions of 1-Oacyl ribofuranoses or 1-halogenoribofuranoses with nucleobases (uracil, thymine, cytosine, adenine, guanine) are generally carried out using rather expensive and strong Lewis acids such as SnCl 4 , (CH 3 ) 3 SiClO 4 , or (CH 3 ) 3 SiOTf, as promotors. Iodotrimethylsilane has also been used for this purpose, even though this reagent is extremely moisturesensitive and expensive [1].…”

“…This reaction appeared to be regioselective, since only the N-1 isomer was obtained for pyrimidine (uracil, thymine, cytosine) and the N-9 for purine (adenine and Nac-guanine). All D-ribofuranosides were characterised by 1 H and 13 C NMR as well as comparison with literature data [3]. The α/β ratio was determined by 1 H-NMR.…”