Nucleophilic substitution at the 4′-position of nucleosides: New access to a promising anti-HIV agent 2′,3′-didehydro-3′-deoxy- 4′-ethynylthymidine

Journal of Organic Chemistry

Volumn 71, Issue 12, 2006, Pages 4433-4438

  Haraguchi, Kazuhiro ^a   Sumino, Masanori ^a   Tanaka, Hiromichi ^a  

^a SHOWA UNIVERSITY   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

ETHYNYLTHYMIDINE; HUMAN IMMUNODEFFICIENCY VIRUS (HIV); NUCLEOPHILIC SUBSTITUTION; NUCLEOSIDES;

AROMATIC COMPOUNDS; MOLECULAR STRUCTURE; SUBSTITUTION REACTIONS; SYNTHESIS (CHEMICAL);

BIOMEDICAL ENGINEERING;

1 (2,5 DIDEOXY BETA GLYCEROPENT 4 ENOFLURANOSYL)THYMINE; 2',3' DIDEHYDRO 3' DEOXY 4' ETHYNYLTHYMIDINE; 4' BENZOYLOXY DERIVATIVE; ALUMINUM CHLORIDE; ANTIRETROVIRUS AGENT; BENZENE DERIVATIVE; FUNCTIONAL GROUP; LEAD; LEAVING GROUP; METHYL ALUMINUM CHLORIDE; NUCLEOSIDE; ORGANOSILICON DERIVATIVE; PROTON; REAGENT; THYMINE DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; DRUG SYNTHESIS; NUCLEOPHILE; NUCLEOPHILIC SUBSTITUTION; STEREOCHEMISTRY; SUBSTITUTION REACTION;

ANTI-HIV AGENTS; INDICATORS AND REAGENTS; NUCLEOSIDES; STAVUDINE; STRUCTURE-ACTIVITY RELATIONSHIP; THYMIDINE;

EID: 33744938155     PISSN: 00223263     EISSN: None     Source Type: Journal    
DOI: 10.1021/jo060194m     Document Type: Article

References (26)

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17. The depicted stereochemistry of 12a was determined by NOE experiment: H-5′b/H-6 (1.7%). Of the two protons at the 5′-position, the one that appears at a higher field is designated as H-5′a, and the other as H-5′b, throughout the text and Experimental Section.
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20. 3-4′ (3.6%).
21. NOE data for 15a (less polar) and 15b (more polar) are as follows: 15a, H-5′a/H-6 (2.5%); 15b, H-5′b/H-6 (3.3%).
22. NOE data for 17a and 17b are as follows: 17a, H-5′b/H-6 (1.3%) and H-5′a/H-6 (1.1%); 17b, H-3′/H-5′a (1.4%).
23. This reagent has been successfully used for the introduction of the trimethylsilylethynyl group to the anomeric position of uracil nucleoside, see: Itoh, Y.; Haraguchi, K.; Tanaka, H.; Gen, E.; Miyasaka, T. J. Org. Chem. 1995, 60, 656.
24. The depicted stereochemistry of 18 was determined by NOE experiment: H-5′a,b/H-6 (6.5%).
25. The bulkiness of aluminum reagent working in this reaction is certainly one important determinant for the observed stereochemical outcome, but it is difficult to know its actual structure.
26. 3/H-6 (0.8%)] as well as by the fact that its H-5′ resonance appeared as a singlet.