Provided herein are improved processes for convening C7-amino-substituted tetracylines to C7-fluoro-substituted tetracyclines as well as intermediates produced by or used in these processes. In one embodiment, a thermal fluorination method is provided in which a suspension comprising a non-polar organic solvent and a C7-diazo-substituted tetracycline hexafluorophosphate, hexafluoarsenate or hexafluorosilicate salt, or a salt, solvate or combination thereof is healed to provide a C7-fluoro-substituted tetracyline, or salt, solvate or combination thereof. In another embodiment, a photolytic fluorination is provided in which a solution comprising an ionic liquid and a C-7diazo-substituted tetracyline tetrafluoroborate, hexafluorophosphate, hexafluoroarsenate or hexafluorosilicate salt, or a salt, solvate or combination thereof is irradiated to provide a C7-fluoro-substituted tetracyline, or salt, solvate or combination thereof.

Methods of synthesizing substituted tetracycline compounds are provided.

Methods of synthesizing substituted tetracycline compounds are provided.

Methods of synthesizing substituted tetracycline compounds are provided.

A method of treating Alcohol Use Disorder (AUD), Substance Use Disorder (SUD), tobacco use, pain, or proinflammatory disorders comprising: providing a subject with an effective amount of a modified tetracycline or derivative thereof to ameliorate or eliminate the AUD, SUD, tobacco use, pain, or proinflammatory disorder, and wherein the modified tetracycline or derivative thereof has reduced binding to a microbial ribosome and has the formula wherein R1 is acetyl, R2 is OH or acetyl, R3 is acetyl, R4 is H or acetyl, and R5 is acetyl.

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The present invention includes novel molecules and methods for using the same to treat Alcohol Use Disorder (AUD), Substance Use Disorder (SUD), tobacco use, pain, or proinflammatory disorders comprising: identifying a subject in need of treatment for at least one of AUD, SUD, pain, or a proinflammatory disorder; and providing the subject with an effective amount of a modified minocycline to ameliorate or eliminate the AUD, SUD, pain, or proinflammatory disorder and that has reduced, or no, antimicrobial activity, wherein the modified tetracycline has a formula, e.g., or the modified doxycycline, minocycline, and tigecycline and their tautomerized structures, where the R-groups shown in the minocycline example above could be different combination of halogen, acetyl ester, methyl ester, and diacetal.

The present invention includes novel molecules and methods for using the same to treat Alcohol Use Disorder (AUD), Substance Use Disorder (SUD), tobacco use, pain, or proinflammatory disorders comprising: identifying a subject in need of treatment for at least one of AUD, SUD, pain, or a proinflammatory disorder; and providing the subject with an effective amount of a modified minocycline to ameliorate or eliminate the AUD, SUD, pain, or proinflammatory disorder and that has reduced, or no, antimicrobial activity, wherein the modified tetracycline has a formula, e.g., or the modified doxycycline, minocycline, and tigecycline and their tautomerized structures, where the R-groups shown in the minocycline example above could be different combination of halogen, acetyl ester, methyl ester, and diacetal.

The present invention pertains, at least in part, to novel substituted tetracycline compounds. These tetracycline compounds can be used to treat numerous tetracycline compound-responsive states, such as bacterial infections and neoplasms.

The present invention pertains, at least in part, to novel substituted tetracycline compounds. These tetracycline compounds can be used to treat numerous tetracycline compound-responsive states, such as bacterial infections and neoplasms.

The tetracycline class of antibiotics has played a major role in the treatment of infectious diseases for the past 50 years. However, the increased use of the tetracyclines in human and veterinary medicine has led to resistance among many organisms previously susceptible to tetracycline antibiotics. The modular synthesis of tetracyclines and tetracycline analogs described provides an efficient and enantioselective route to a variety of tetracycline analogs and polycyclines previously inaccessible via earlier tetracycline syntheses and semi-synthetic methods. These analogs may be used as anti-microbial agents or anti-proliferative agents in the treatment of diseases of humans or other animals.