D-Arbinose-Based Synthesis of homo-C-d4T and homo-C-thymidine

Abstract

2,3,5-Tri-O-benzyl-D-arabinofuranosyl halides (chloride, bromide) were reacted with AllMgBr, MeMgBr, and VinMgBr to furnish anomeric mixtures of the C-glycosyl products. The factors that influenced the β/α ratio are discussed. The α,β-C-vinyl derivative was transformed into 1-deoxy-1-C-hydroxymethyl-β- and -α-D-arabinofuranoses (2,5-anhydro-D-glucitol and -mannitol, respectively), separable after isopropylidenation step. 2,5-Anhydro-1,3-O-isopropylidene-D-glucitol was converted into 2,5-anhydro-6-O-triphenylmethyl-D-erythro-hex-3,4-enitol and 2,5-anhydro-4,6-di-O-benzoyl-3-deoxy-D-ribo-hexitol, which were coupled with N-3-benzoylthymine under the Mitsunobu conditions to furnish two analogs of nucleosides with a -CH₂- insert between sugar moieties and thymine.

Keywords:

• D-arabinose, deoxygenation
• C-glycoside
• Grignard reagents
• Mitsunobu coupling
• C-nucleoside
• stereoselectivity

Acknowledgments

Prof. Alexander Y. Nazarenko, Chemistry Department, State University of New York, College at Buffalo, USA, is acknowledged for x-ray structure of 4; Dr. Kent Dailey, Brigham Young University, Provo, UT, USA, for permission to use the x-ray facilities; Prof. Francesco Nicotra, Department of Chemistry, University of Milano-Bicocca, Italy for the NMR data of 27α; and Prof. Peter G. Goekjian, Department of Chemistry, University Claude Bernard Lyon 1, Villeurbanne, France, for helpful discussion. Financial support from the Brazilian National Research Council is appreciated.