Akemi Toyota

Mitsunobu Reactions for the Synthesis of Carbocyclic Analogues of Nucleosides: Examination of the Regioselectivity1

Abstract In order to provide a general synthetic method for carbocyclic nucleosides, regioselectivities in Mitsunobu reaction of purine, pyrimidin-2-one and their substituted derivatives with a variety of alcohols were examined and found to depend upon both substituents of the bases and kind of the alcohols.

The Alkylation of 2-Amino-6-chloropurine with Alcohols by Mitsunobu Reaction for a Synthesis of Carbocyclic Guanosine Analogs

Mitsunobu reaction of 2-amino-6-chloropurine with various alcohols which provides a convenient method for a synthesis of carbocyclic or acyclic guanosine analogs is described

Synthesis of (1R, 4S, 5R)-9-(4,5-bishydroxy-methylcyclopent-2-en-1-yl)-9H-adenine [(-)-BCA] and selective inhibition of human immunodeficiency virus☆

Abstract (1 R ,4 S ,5 R )-9(4,5-Bishydroxymethylcyclopent-2-en-1-yl)-9 H -adenine [(-)-BCA] has been synthesized from (-)-Corey lactone in 11 steps and shown to have potent and selective effects against human immmunodeficiency virus type 1. The result demonstrated that the potent-HIV activity of racemic BCA obtained in our previous work is expressed solely by the (1 R ,4 S ,5 R )-(-)-isomer.

A novel stereoselective synthesis of cis-2-fluorocyclopropane-1-carboxylic acid

A novel method consisting four-step from tert-butyl acrylate (4) and chloromethyl phenyl sulfoxide (5) for preparing cis-2-fluorocyclopropane-1-carboxylic acid (cis-3) was elaborated. The method involves initial formation of the cis-2-phenylsulfinylcyclopropanecarboxylate (cis-6), fluorination by molecular fluorine to trans-7, reductive desulfonylation to the ester (cis-9) and acid-catalyzed hydrolysis to the final product (cis-3).

Addition of molecular fluorine to 2-azabicyclo[2.2.1]hept-5-en-3-one and related compounds: Synthesis of difluorinated carbocyclic nucleosides

Abstract Addition of molecular fluorine to bicyclo[2.2.1]hept-2-ene derivatives having electronegative substituent(s) on the ethano bridge has been found to give exo,exo -difluoro adducts with high stereoselectivity. The difluoro adducts derived from 2-azabicyclo[2.2.1]hept-5-en-3-ones having an electron-withdrawing group at 2-position were converted to the difluorinated carbocyclic nucleoside analogs.

Addition of molecular fluorine to bicyclo[2.2.1]hept-2-ene derivatives and conversion to fluorine-containing carbocyclic nucleosides

Abstract Addition of molecular fluorine to bicyclo[2.2.1]hept-2-ene derivatives has been found to give exo,exo -difluoro adducts in fair yields. The difluoro adduct ( 13c ) was converted to the fluorine containing carbocyclic adenosine and guanosine analogs.

α-Fluorination of 6-phenylsulfinyl-2-azabicyclo[2.2.1]heptan-3-one and synthesis of 2′-fluoro substituted carbovir

Fluorination of phenylsulfinyl bicycloamide using molecular fluorine proceeded preferentially with inversion of the carbon atom having the sulfinyl group to afford α-fluorinated sulfonyl bicycloamide in fair yield. The fluorinated sulfonyl bicycloamide was converted to 2′-fluoro substituted carbovir via reductive desulfonylchlorination.

Synthesis of enantiomerically pure 4-acetoxy-2-fluoro-2-cyclopenten-1-one

Abstract Addition of molecular fluorine to cis-2-cyclopentene-1,4-diol gave the cis-anti adduct stereoselecrively. This meso diol was dissymmetrized by means of acetylation under lipase catalysis to afford the monoacetate with a high enatiomeric purity. Oxidation of the monoacetate followed by elimination of hydrogen fluoride under basic conditions furnished the titled compound which is an attractive building block for chiral fluorinated molecules.

Synthesis of 9-(C-5-hydroxy-C-4-hydroxy-methylcyclopent-2-en-R-1-yl)-9H-adenine [(±)-Epinor-BCA]

9-(c-5-Hydroxy-c-4-hydroxymethylcyclopent-2-en-r-1-yl)-9H-adenine [(±)-Epinor-BCA] has been synthesized from the bicyclic hydroxy lactone (2) in eleven steps

Resolution of 9-(c-4,t-5-bishydroxymethylcyclopent-2-en-r-1-yl)-9H-adenine and selective inhibition of human immunodeficiency virus by the (−) enantiomer

Two enantiomers of 9-(c-4,t-5-bishydroxymethylcyclopent-2-en-r-1-yl)-9H- adenine (BCA) which showed a potent and selective anti-HIV effects have been synthesized and evaluated against human immunodeficiency virus type 1. The result demonstrated that the potent-HIV activity of racemic BCA is expressed solely by the (-) isomer.