Desmethyl(trifluormethyl)actinomycine

Demethyl(trifluoromethyl)actinomycins The synthesis of new 4-(trifluoromethyl)benzoic acid derivatives 2–10 and their coupling with amino acids and peptides 12, 13, 15 is described. They serve as precursors for the synthesis of the hitherto unknown demethyl(trifluoromethyl)actinocin dimethyl esters 11, demethyl-trifluoromethyl-actino-cinyl peptides 14, 16, 18 and the demethyl-trifluoromethyl-actinomycins 17. Although spacially comparable with the methyl residues, the 4- and 6-trifluoromethyl groups have unexpected strong influences on the antibiotic and cytostatic properties of the actinomycins. The CH3/CF3 exchange makes it possible to bring NMR-analytically useful hetero nuclei into the centre of the actinomycin/DNA complex (Figure 1).

[1]  H. Seto,et al.  Preparation of fluorinated antibiotics followed by 19F NMR spectroscopy. II. Fluorinated actinomycins. , 1985, The Journal of antibiotics.

[2]  P. Beak,et al.  The tertiary amide as an effective director of ortho lithiation , 1982 .

[3]  P. Callery,et al.  A convenient synthesis of quinones from hydroquinone dimethyl ethers. Oxidative demethylation with ceric ammonijm nitrate. , 1976, The Journal of organic chemistry.

[4]  H. Lackner.  Die Raumstruktur der Actinomycine , 1975 .

[5]  H. Lackner.  Three-dimensional structure of the actinomycins. , 1975, Angewandte Chemie.

[6]  J. Meienhofer,et al.  Structure-activity relationships in the actinomycins. , 1973, Advances in applied microbiology.

[7]  H. Lackner.  Synthesen von selektiv deuterierten Pentapeptidlactonen und stellungsspezifisch in (α)- oder (β)-Peptidring markierten Actinomycinen , 1971 .

[8]  F. Seela,et al.  Actinomycine. XXXVI; Synthesen von Actinomycinen und actinomycinähnlichen Chromopeptiden, IX 4.6‐Didesmethyl‐actinomycin C1 und dessen 4.6‐Dimethoxy‐, 4.6‐Diäthyl‐ und 4.6‐Di‐tert.‐butyl‐Derivat , 1971 .

[9]  H. Lackner.  Actinomycine, XXXV; Synthesen von Actinomycinen und actinomycin‐ähnlichen Chromopeptiden, VIII. Totalsynthese von aniso‐Actinocinyl‐peptiden und aniso‐Actinomycinen über deuterium‐markierte Vorstufen , 1970 .

[10]  J. Meienhofer.  Syntheses of actinomycin and analogs. 3. A total synthesis of actinomycin D (Cl) via peptide cyclization between proline and sarcosine. , 1970, Journal of the American Chemical Society.

[11]  H. Lackner,et al.  Actinomycine, XXXIII; Synthesen von Actinomycinen und actinomycinähnlichen Chromopeptiden, VI. Totalsynthese der Actinomycine C1, C2, i‐C2 und C3 über N‐[2‐Amino‐3‐hydroxy‐4‐methyl‐benzoyl]‐pentapeptidlactone; ein weiterer Beweis für die Bis‐pentapeptid‐Struktur der Actinomycine , 1968 .

[12]  H. Lackner,et al.  Actinomycinen, XXXI; Synthesen von Actinomycinen und actinomycin- ähnlichen Chromopeptiden, V. Aufbau von Actinomycinen über Actinomycinsäuren; ein zweiter Syntheseweg , 1968 .

[13]  D M Crothers,et al.  Studies of the binding of actinomycin and related compounds to DNA. , 1968, Journal of molecular biology.

[14]  H. Lackner,et al.  Actinomycine, XXVIII; Synthesen von Actinomycinen und actinomycin‐ähnlichen Chromopeptiden, III. Totalsynthese von Actinomycin C3 über Bis‐seco‐actinomycin C3 , 1967 .

[15]  H. Lackner,et al.  Actinomycine, XXXIV. Synthesen von Actinomycinen und actinomycinähnlichen Chromopeptiden, VII. Pseudo-actinocinyl-bis-L-threonin , 1966 .

[16]  H. Musso,et al.  Phenoxazine, VIII. Über den Mechanismus der Kehrmannschen Phenoxazonsynthese. IR‐spektroskopische Studien an isotopen Triphendioxazinen , 1965 .

[17]  G. M. L. Fave.  Some Reactions of the Trifluoromethyl Group in the Benzotrifluoride Series. I. Hydrolysis , 1949 .

[18]  R. Jones.  Ortho and para substituted derivatives of benzotrifluoride. , 1947, Journal of the American Chemical Society.

[19]  H. B. Woodruff,et al.  Bacteriostatic and Bactericidal Substances Produced by a Soil Actinomyces.∗ , 1940 .