Tadashi Miyasaka

“Umpulong” of reactivity at the C-6 position of uridine: a simple and general method for 6-substituted uridines

Abstract Lithiated 2′,3′-O-isopropylidine-5′- O -methoxymethyl-uridine was found to react with a variety of electrophilic reagents regiospecifically at the C-6 position. The protecting groups of the ribose moiety in the 6-functionalized products were concurrently removed under mild conditions with aqueous trifluoroacetic acid. Consequently, the present method permits simple and general syntheses of 6-substituted uridines.

Cleavage of a nucleosidic oxetane with carbanions: synthesis of a highly promising candidate for anti-HIV agents — a phosphonate isostere of AZT 5′-phosphate

Abstract A phosphonate analogue of 3′-azido-3′-deoxythymidine (AZT) 5′-phosphate was synthesized via nucleophilic ring-opening of a nucleosidic oxetane with (RO) 2 POCH 2 Li as a key reaction step.

Hept Derivatives: 6-Benzyl-1-ethoxymethyl-5-isopropyluracil (MKC-442)

Abstract The 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) derivatives have been found to be potent and specific inhibitors of human immunodeficiency virus type 1 (HIV-1) replication in vitro. Among the compounds, MKC-442 (6-benzyl-1-ethoxymethyl-5-isopropyluracil) has recently been chosen as a candidate for clinical efficacy and safety studies in patients with the acquired immune deficiency syndrome (AIDS).

A simple and general entry to 5-substituted uridines based on the regioselective lithiation controlled by a protecting group in the sugar moiety

Abstract Lithiation of 2′,3′,5′-tris- O -( tert -butyldimethylsilyl)uridine with sec -BuLi/TMEDA occurs at the C-5 position with a high regioselectivity and subsequent reactions of the resulting C-5 lithiated species with a variety of electrophiles provides a general entry to 5-substituted uridines.

Electrophilic addition to 4-thio furanoid glycal: a highly stereoselective entry to 2′-deoxy-4′-thio pyrimidine nucleosides

Abstract 4-Thio furanoid glycals with different types of O -silyl protection have been prepared from benzyl 3,5-di- O -benzyl-2-deoxy-1,4-dithio-d- erythro -pentofuranoside. Face-selectivity for PhSeCl- or N -iodosuccimide-initiated addition of a pyrimidine base to the thioglycal was found to be controlled by O -silyl protecting groups. Using the thioglycal protected with a 3,5- O -di- t -butylsilyl group, a highly stereoselective synthesis of β-2′-deoxy-4′-thio pyrimidine nucleosides has been accomplished.

Synthesis and Biological Evaluation of 1′-C-Cyano-Pyrimidine Nucleosides †

Abstract 2′-Deoxy-, 2′-bromo-, and arabino-1′-C-cyano-pyrimidine nucleosides were synthesized from O2 ,2′-cyclouridine. Incorporation of cyano group at the anomeric position was achieved by treatment of 1′,2′-unsaturated uridine with NBS in the presence of pivalic acid followed by TMS-cyanide and stannic chloride. Antineoplastic and antiviral activities of those compounds are also discussed. †This paper is dedicated to Dr. Yoshihisa Mizuno on the occasion of his 75th birthday.

Regiospecific C-alkylation of uridine: a simple route to 6-alkyluridines

Abstract 6-Alkyluridines were conveniently synthesized by lithiation and successive alkylation from 2′,3′-O-isopropylideneuridine with complete regioselectivity.

Preparation and reactions of 2'- and 3'-vinyl bromides of uracil-nucleosides : versatile synthons for anti-hiv agents

Abstract Bromination and successive oxidation of 1-[5- O -( t -butyldiphenyl-silyl)-3-deoxy-3-phenylseleno-β-D-xylofuranosyl]uracil yields the 2′- and 3′-vinyl bromides, which serve as synthons for 2′- or 3′-substituted 2′,3′-dide-hydro 2′,3′ -dideoxyuridines via palladium-catalyzed cross-coupling or the halogen lithium exchange reaction.

Dynamic aspects in the LDA lithiation of an arabinofuranosyl derivative of 4-ethoxy-2-pyrimidinone: Regioselective entry to both C-5 and C-6 substitutions

Abstract Regioselectivity (C-5 vs. C-6) in the LDA lithiation of 1-[2,3,5-tris- O -( tert -butyldimethylsilyl)--β-D-arabinofuranosyl]-4-ethoxy-2-pyrimidinone can be controlled simply by changing the reaction conditions, providing a route to both the 5- and 6-substituted derivatives.

Nucleosidic enol esters: A versatile tool for the synthesis of 3′-carbon-substituted nucleosides

Abstract Enol esters of uracil and adenine nucleosides prepared by selenoxide fragmentation of the corresponding 3′-phenylseleno derivatives have been shown to yield 3′-carbon-substituted products upon reacting with MeLi followed by electrophiles, providing the first example of the aldol reaction in this field.