Carbonyl to methylene conversions at the tricarbonyl-portion of ascomycin derivatives

Tetrahedron Letters

Volumn 40, Issue 44, 1999, Pages 7761-7764

  Baumann, Karl ^a   Knapp, H ^a   Strnadt, G ^a   Schulz, G ^a   Grassberger, M A ^a  

^a Novartis Forschungsinstitut ^*  (Austria)

Author keywords

[No Author keywords available]

Indexed keywords

10 DEOXOASCOMYCIN; 10 DEOXOASCOMYCIN A; 10 DEOXOASCOMYCIN B; 10 DEOXOASCOMYCIN C; 9 DEOXOASCOMYCIN; 9 DEOXOASCOMYCIN A; 9 DEOXOASCOMYCIN B; 9 DEOXOASCOMYCIN C; ASCOMYCIN; ASCOMYCIN DERIVATIVE; CARBONYL DERIVATIVE; HYDROGEN SULFIDE; N,N DIMETHYLFORMAMIDE; PYRIDINE; TERT BUTYLDIMETHYLSILYLOXYASCOMYCIN; UNCLASSIFIED DRUG;

ARTICLE; CHEMICAL MODIFICATION; DRUG SYNTHESIS; PROTEIN DOMAIN;

EID: 0033615789     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(99)01622-6     Document Type: Article

References (21)

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15. 7. In a typical run, a solution of the starting material (Immol of 1,3 or 4) and 3ml pyridine (37mmol) in 30ml dimethyl formamide was treated with a stream of dihydrogen sulfide at room temperature for three hours. After additional twenty hours at ambient temperature, the mixture was concentrated at reduced pressure and partitioned between brine and ethyl acetate. The organic layer was dried over sodium sulfate, filtered and evaporated to dryness. The residual oil was subjected to column chromatography (silica gel, eluent: n-heptane : ethyl acetate = 1:3 => 1 :5 for 5a/6a; 1:1 =>1 : 2 for 5b/6b and 4 : 1 => 2 : 1 for 5c/6c ) to give the title compounds according table 1.
16. 8. A multi-step synthesis of 9-deoxo-ascomycin (5a) utilizing radical chemistry has been described earlier, see: Emmer, Gerhard; Weber-Roth, Sabine. Tetrahedron 1992, 48, 5861.
17. 3); 9,53 (25-methyl).
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21. 11. The methodology is applicable to ascomycin-, FK 506- and rapamycin derivatives bearing an intact tricarbonyl domain.