Naoko Hirose

Radical deoxygenation and dehalogenation of nucleoside derivatives with hypophosphorous acid and dialkyl phosphites

Hypophosphorous acid and dialkyl phosphites are effective radical reducing agents for O-thiocarbonyl groups or halides at the sugar part of nucleoside derivatives and give the corresponding hydrocarbons in high yield.

Convenient synthesis of fluorinated nucleosides with perfluoroalkanesulfonyl fluorides.

ABSTRACT Perfluoroalkanesulfonyl fluorides are effective dehydroxy-fluorination agents for the hydroxyl group at the sugar moiety of nucleoside derivatives and give the corresponding fluorinated nucleosides in good yield with an inversion of configuration in a single step.

Improved synthesis of 9-(2,3-dideoxy-2-fluoro-β-d-threo-pentofuranosyl)adenine (FddA) using triethylamine trihydrofluoride

Abstract An improved synthesis of 9-(2,3-dideoxy-2-fluoro-β- d - threo -pentofuranosyl)adenine ( 1 , FddA) via a fluorination of 3′- O -benzoyl-5′- O -tritylriboside ( 4a ) using noncorrosive triethylamine trihydrofluoride (Et 3 N·3HF) is described. The method is suitable for large-scale synthesis. In particular, the synthesis of the pivotal intermediate 4a was much improved in avoidance of the use of toxic tin reagent. Radical deoxygenation with several silanes was also studied. The total yield of FddA from 6-chloropurine riboside ( 2 ) in this study was greater than that we reported previously.

Practical synthesis of α-aminoalkyl-α′-chloromethylketone derivatives. Part 1: Chloromethylation of N-protected 3-oxazolidin-5-ones

Abstract Reaction of N-protected 3-oxazolidin-5-ones with in situ-generated chloromethyllithium afforded N-protected 5-chloromethyl-5-hydroxy-3-oxazolidines without racemization. They were easily hydrolyzed to give α-aminoalkyl-α′-chloromethylketone derivatives, which are useful intermediates for several protease inhibitors.

Practical synthesis of α-aminoalkyl-α′-chloromethylketone derivatives. Part 2: Chloromethylation of N-imine-protected amino acid esters

Abstract Chloromethylation of N -imine-protected amino acid esters followed by acid hydrolysis gave α-aminoalkyl-α′-chloromethylketone as a HCl salt form in good yield without racemization. The amino group was conveniently protected with carbamate protecting reagents to give various useful intermediates for the protease inhibitors.

Practical synthesis of 9-(2,3-dideoxy-2-fluoro-β-d-threo-pentofuranosyl)adenine (FddA) via a purine 3′-deoxynucleoside

Abstract A practical synthesis of 9-(2,3-dideoxy-2-fluoro-β- d - threo -pentofuranosyl)adenine ( 1 , FddA) via a 6-chloro-9-(3-deoxy-β- d - erythro -pentofuranosyl)-9 H -purine ( 6 ) is described. Fluorination at the C2′-β position of the purine 3′-deoxynucleoside was improved by the introduction of 6-chloro group, and proceeded in moderate yield. The total yield of FddA from readily available starting material 6 was 35%.

Dihalomethylation of N-protected phenylalanine esters

Abstract Dihalomethylation of several N-protected amino acid esters gave N-protected α-aminoalkyl-α′-dihalomethylketones, which are useful intermediates for the synthesis of erythro β-amino-α-hydroxycarboxylic acids, in good yield. The dihalomethylketones were successfully converted to N-protected α-aminoalkyl-α′-halomethylketones by selective catalytic hydrogenation.

Synthesis and in vitro antiviral activity evaluation of 9-(2-azido-2,3-dideoxy-beta-D-threo-pentofuranosyl)adenine derivatives.

9-(2-Azido-2,3-dideoxy-β-D-threo-pentofuranosyl)adenine derivatives (1a–e) containing a lipophilic function at the N-6 position in the purine ring were prepared and evaluated for their antiviral activity. The compounds 1a–e turned out to be inactive as antiviral agents.

Synthesis of Fluorinated Nucleosides

Two practical synthetic approaches to the production of lodenosine [FddA, 9‐(2,3‐dideoxy‐2‐fluoro‐β‐D‐threo‐pentofuranosyl)adenine] via 6‐chloropurine riboside or 6‐chloropurine 3′‐deoxyriboside are described. The reaction sequence contains new fluorination methods and new applications of radical reduction. The reagents and reaction conditions of each step have been carefully selected to ensure robustness and safety.