The present invention pertains to novel 3, 10 and/or 12a-substituted tetracycline compounds. These tetracycline compounds can be used to treat numerous tetracycline compound-responsive states, such as bacterial infections and neoplasms, as well as other known applications for minocycline and tetracycline compounds in general, such as blocking tetracycline efflux and modulation of gene expression. Methods of preparing the novel 3, 10 and/or 12a-substituted tetracycline compounds are also disclosed.