Kazuhiro Asami

Publications (3)12.99 Total impact

• Article: Design and synthesis of isonucleosides constructed on a 2-oxa-6-thiabicyclo[3.2.0]heptane scaffold.

  Yuichi Yoshimura, Kazuhiro Asami, Tomozumi Imamichi, Tomoko Okuda, Kimiyasu Shiraki, Hiroki Takahata
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  ABSTRACT: A novel method for the design and synthesis of an isonucleoside containing a 2-oxa-6-thiobicyclo[3.2.0]heptane skeleton is described. 2,2-Dimethyl-1,3-dioxan-5-one 13 was converted into a dioxabicyclohexane derivative in six steps. After cleavage of the epoxide group with a thiol (thiophenol or PMB mercaptan), the resulting product was subjected to the Mitsunobu reaction in the presence of a nucleobase. The reaction proceeded via the migration of the thiosulfide groups and gave the desired isonucleoside derivatives. In the case of a phenyl sulfide derivative, radical desulfurization followed by deprotection gave 4'-substituted 2',3'-dideoxyisonucleosides. A PMB sulfide derivative, on the other hand, was converted into the corresponding dimesylate, which was then treated with mercury acetate and trifluoroacetic acid to remove the PMB group. The resulting thiol derivative was treated with DBU to give the desired isonucleoside constructed on a 2-oxa-6-thiobicyclo[3.2.0]heptane scaffold after deprotection. The optimized conformer of the isonucleoside was calculated using DFT at the B3LYP/6-31G** level and was compared with that of lamivudine using model compounds.
  The Journal of Organic Chemistry 06/2010; 75(12):4161-71. · 4.45 Impact Factor
• Article: New synthesis of (+/-)-isonucleosides.

  Yuichi Yoshimura, Kazuhiro Asami, Hiromitsu Matsui, Hiromichi Tanaka, Hiroki Takahata
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  ABSTRACT: [Structure: see text] A novel method for synthesizing isonucleosides, a new class of anti-HIV nucleosides, is described. 2,2-Dimethyl-1,3-dioxan-5-one was converted into a dioxabicyclohexane derivative in six steps. After cleaving the epoxide group with thiophenol, the resulting product was subjected to the Mitsunobu reaction in the presence of a nucleobase to give the desired isonucleoside derivative via migration of the thiophenyl group. Removal of the thiophenyl group under radical conditions followed by deprotection led to the 4'-substituted 2',3'-dideoxyisonucleosides as a racemic mixture.
  Organic Letters 01/2007; 8(26):6015-8. · 5.86 Impact Factor
• Article: A practical synthesis of 4′-thioribonucleosides

  Yuichi Yoshimura, Tetsuya Kuze, Mari Ueno, Fumiko Komiya, Kazuhiro Haraguchi, Hiromichi Tanaka, Fumitaka Kano, Kohei Yamada, Kazuhiro Asami, Nobuaki Kaneko, Hiroki Takahata
  Tetrahedron Letters 47(4):591-594. · 2.68 Impact Factor