Synthesis of novel iso-4-thionucleosides using the Mitsunobu reaction

Journal of Organic Chemistry

Volumn 63, Issue 20, 1998, Pages 6891-6899

  Yamada, Kohei ^a   Sakata, Shinji ^a   Yoshimura, Yuichi ^a  

^a YAMASA CORPORATION   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

ARABINITOL; BENZYLTHIOURACIL; GLUCOSE; NUCLEIC ACID BASE; NUCLEOSIDE DERIVATIVE; PURINE NUCLEOSIDE; PYRIMIDINE DERIVATIVE; SULFONIUM DERIVATIVE;

ALKYLATION; ARTICLE; CHEMICAL REACTION; DRUG STRUCTURE; DRUG SYNTHESIS; ISOMER; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; NUCLEAR OVERHAUSER EFFECT;

EID: 0032476077     PISSN: 00223263     EISSN: None     Source Type: Journal    
DOI: 10.1021/jo980667s     Document Type: Article

References (23)

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16. The Mitsunobu reaction of the 3-O-benzoyl derivative, instead of 13, with 6-chloropurine gave an undesired a-isonucleoside, stereo-selectively, the stereochemistry of which was determined by NOE experiments. This result suggests that the more electron-withdrawing benzoyl group at the 3-position makes the carbon at the 2-position electron deficient, thus potentiating the external nucleophilic attack.
17. Contrary to our expectation, when tributylphosphine was used instead of triphenylphosphine, the reaction was not complete in THF at 50 °C even after 44 h. Only α-14a was obtained in 11% yield with a recovery of 13 in 32% yield.
18. The undesired N7-adduct of 6-chloropurine was not obtained. Similarly, none of the N7-adducts were found in the reaction of the other purine bases. The structure of N9-adducts were confirmed by UV spectra after being converted to the deblocked compounds.
19. Although the reaction mixture became clear when DMF was used as a solvent, there was also no reaction (cf. Table 1, entry 6).
20. 1H NMR spectra of α- and β-15, the resonance of the H-2′ proton in the β-isomer was shifted upfield compared with that in the α-isomer.
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23. Antiviral activities, except against HIV, and cytotoxicity were assayed at the Biological Laboratory of Yamasa Corp. Anti-HIV activity was tested at the Rational Drug Design Laboratories, Fukushima, Japan. We greatly appreciate their assistance.