The present disclosure relates to stereodefined polycyclic (e.g., tetracyclic) compounds that contain quaternary centers at one or multiple ring fusions, synthetic methods for preparing such compounds. In one aspect, the present disclosure relates to preparing a C9-alpha-substituted or a C9-beta-substituted compound (steroid numbering), the method comprising the steps of providing a tertiary allylic substrate and performing a regio- and stereoselective cyclization reaction to form a C9-C10 bond and to set a quaternary center at C9.

The invention provides a novel, general, and facile strategy for the creation of small molecules with high structural and stereochemical complexity. Aspects of the methods include ring system distortion reactions that are systematically applied to rapidly convert readily available natural products to structurally complex compounds with diverse molecular architectures. Through evaluation of chemical properties including fraction of sp.sup.3 carbons, ClogP, and the number of stereogenic centers, these compounds are shown to be significantly more complex and diverse than those in standard screening collections. This approach is demonstrated with natural products (gibberellic acid, adrenosterone, and quinine) from three different structural classes, and methods are described for the application of this strategy to any suitable natural product.

The present disclosure relates to synthetic methods for preparing a 9-alpha-substituted or a 9-beta-substituted steroid-like compound. In particular, the disclosure relates to methods for generating a steroidal C9-C10 bond and establishing stereochemistry at C9 in such compounds. The methods provide high levels of stereoselection in the C9-C10 bond forming process. Compounds synthesized by such methods can be used as nuclear hormone receptor modulators.

The present disclosure is generally directed to neuroactive enantiomeric 15-, 16- and 17-substituted steroids with additional optional substituents at carbons 3, 4, 6, 7, 10 and 13, and pharmaceutically acceptable salts thereof, for use as, for example, modulators for GABA type-A receptors. The present disclosure is further directed to pharmaceutical compositions comprising such compounds.

The present invention relates to a new process for the synthesis of 17-hydroxy-des-A-androst-9,10-en-5-one, the compound of the following formula (1), which can be used as an intermediate in the synthesis of retroprogesterones.

The present disclosure relates to stereodefined polycyclic (e.g., tetracyclic) compounds that contain quaternary centers at one or multiple ring fusions, synthetic methods for preparing such compounds, and methods of using such compounds to treat a disease, such as a brain tumor and, particularly, a glioma.

The present invention relates to a new process for the synthesis of 17-hydroxy-des-A-androst-9,10-en-5-one, the compound of the following formula (1), which can be used as an intermediate in the synthesis of retroprogesterones.

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The invention a novel, general, and facile strategy for the creation of small molecules with high structural and stereochemical complexity. Aspects of the methods include ring system distortion reactions that are systematically applied to rapidly convert readily available natural products to structurally complex compounds with diverse molecular architectures. Through evaluation of chemical properties including fraction of sp.sup.3 carbons, ClogP, and the number of stereogenic centers, these compounds are shown to be significantly more complex and diverse than those in standard screening collections. This approach is demonstrated with natural products (gibberellic acid, adrenosterone, and quinine) from three different structural classes, and methods are described for the application of this strategy to any suitable natural product.

Provided are steroid analogues functionalized with polar substituents at the C3 and/or C20 positions of the steroid ring system that exhibit improved water solubility. Also provided are pharmaceutical compositions comprising the steroid analogues and methods using the novel steroid analogues for the treatment and prevention of neurodegeneration in a patient following injury to the central nervous system.

The present disclosure relates to polycyclic (e.g., fused tetracyclic) liver X receptor (LXR) modulators, synthetic methods for preparing such LXR modulators, and methods of using such LXR modulators to treat a disease or condition that would benefit from LXR modulation. Exemplary compounds have quaternary centers at C9 and C13 and a substituted sulfonamide moiety at C16.