Efficient stereoselective synthesis of cis, syn-hydroxyitraconazole isomers

Tetrahedron Letters

Volumn 38, Issue 45, 1997, Pages 7839-7842

  Tanoury, Gerald J ^a   Senanayake, Chris H ^a   Hett, Robert ^a   Hong, Yaping ^a   Wald, Stephen A ^a  

^a DAINIPPON SUMITOMO PHARMA CO LTD   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

ITRACONAZOLE;

ANTIFUNGAL ACTIVITY; ARTICLE; CHIRALITY; CIS ISOMER; DRUG STRUCTURE; STEREOCHEMISTRY; STRUCTURE ANALYSIS;

EID: 0030727158     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(97)10129-0     Document Type: Article

References (23)

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12. 4 - 0.1% TEA (pH 3.0)/acetonitrile (55:45), 1.0 mL/min, 260 nm, 1.9 min).
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14. 3/18-crown-6 in DMF provided a mixture of isomers.
15. 13C NMR and mass spectral.
16. 4 - 0.1% TEA (pH 3.0)/acetonitrile (55:45), 1.0 mL/min, 260 nm, 9.7 min).
17. Rapid access was gained to the cis,anti isomers of 2 for biological evaluation from the meso isomer of 5 and each cis-dioxolane enantiomer of 3. As outlined below, using meso-5 and (2R,4R)-3 gave a 1:1 mixture of (2R,4S,2′R*,3′R*)-hydroxyitraconazole isomers, and using (25,4S)-3 gave the other pair of cis,anti isomers, (2S,4R,2′R*,3′R*)-hydroxyitraconazole. (formula presented)
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23. Attempts to directly alkylate 10 with a cyclic sulfate were unsuccessful. (formula presented)