7-iodo tetracyclines and related methods
View Patent ↗7-substituted fused ring tetracycline compounds, methods of treating tetracycline responsive states, and pharmaceutical compositions containing the 7-substituted fused ring tetracycline compounds are described.
1. A method for synthesizing 7-iodo sancycline, 7-iodo oxytetracycline, 7-iodo methacycline, 7-iodo doxycycline or 7-iodo tetracycline, comprising:
treating unsubstituted sancycline, unsubstituted oxytetracycline, unsubstituted methacycline, unsubstituted doxycycline or unsubstituted tetracycline, respectively with at least one equivalent of N-iodosuccinimide in trifluoroacetic acid thereby synthesizing 7-iodo sancycline, 7-iodo oxytetracycline, 7-iodo methacycline, 7-iodo doxycycline or 7-iodo tetracycline.
2. The method of claim 1 , wherein the treatment with at least one equivalent of N-iodosuccinimide in trifluoroacetic acid is initially carried out at 0° C.
3. The method of claim 2 , wherein the treatment with at least one equivalent of N-iodosuccinimide in trifluoroacetic acid initially carried out at 0° C. is subsequently warmed to room temperature.
4. The method of claim 3 , further comprising quenching of the reaction.
5. The method of claim 1 , further comprising purifying the resultant 7-iodo sancycline, 7-iodo oxytetracycline, 7-iodo methacycline, 7-iodo doxycycline or 7-iodo tetracycline.
6. The method of claim 1 , wherein 7-iodo sancycline is synthesized by treating unsubstituted sancycline with at least one equivalent of N-iodosuccinimide in trifluoroacetic acid.
7. The method of claim 1 , wherein 7-iodo oxytetracycline is synthesized by treating unsubstituted oxytetracycline with at least one equivalent of N-iodosuccinimide in trifluoroacetic acid.
8. The method of claim 1 , wherein 7-iodo methacycline is synthesized by treating unsubstituted methacycline with at least one equivalent of N-iodosuccinimide in trifluoroacetic acid.
9. The method of claim 1 , wherein 7-iodo doxycycline is synthesized by treating unsubstituted doxycycline with at least one equivalent of N-iodosuccinimide in trifluoroacetic acid.
10. The method of claim 1 , wherein 7-iodo tetracycline is synthesized by treating unsubstituted tetracycline with at least one equivalent of N-iodosuccinimide in trifluoroacetic acid.
11. A method for synthesizing 7-iodo sancycline comprising:
treating unsubstituted sancycline with at least one equivalent of N-iodosuccinimide in trifluoroacetic acid, thereby synthesizing 7-iodo sancycline.
12. The method of claim 11 , wherein the treatment with at least one equivalent of N-iodosuccinimide in trifluoroacetic acid is initially carried out at 0° C.
13. The method of claim 12 , wherein the treatment with at least one equivalent of N-iodosuccinimide in trifluoroacetic acid initially carried out at 0° C. is subsequently warmed to room temperature.
14. The method of claim 13 , further comprising quenching of the reaction.
15. The method of claim 14 , further comprising purifying the resultant 7-iodo sancycline.
16. The method of claim 11 , wherein 1.2 equivalents of N-iodosuccinimide in trifluoroacetic acid are used.
17. The method of claim 12 , wherein the treatment is carried out at 0° C. for forty minutes.
18. The method of claim 13 , wherein the treatment is carried out at room temperature for five hours.