The present invention relates to a novel method for producing fluorinated cycloaliphatic compounds from the analogous aromatic compounds by hydrogenation with an Rh-carbene catalyst system.

Embodiments of the present disclosure relate generally to the analysis of broad metabolic changes associated with neurological disorders. In particular, the present disclosure provides materials and methods relating to the use of metabolomics as a biochemical approach to identify peripheral metabolic changes and corresponding metabolic biomarkers of neurological disorders. Embodiments of the present disclosure include the use of bile acids and their derivatives as metabolic biomarkers to aid in the determination of whether a subject suffers from, or is at risk of developing, a neurological disorder, such as Alzheimer's Disease (AD).

Embodiments of the present disclosure relate generally to the analysis of broad metabolic changes associated with neurological disorders. In particular, the present disclosure provides materials and methods relating to the use of metabolomics as a biochemical approach to identify peripheral metabolic changes and corresponding metabolic biomarkers of neurological disorders. Embodiments of the present disclosure include the use of bile acids and their derivatives as metabolic biomarkers to aid in the determination of whether a subject suffers from, or is at risk of developing, a neurological disorder, such as Alzheimer's Disease (AD).

Methods are provided for the epigenetic analysis of cell-free DNA using organic boranes to convert oxidized 5-methylcytosine residues in the cell-free DNA to dihydrouracil (DHU) residues. Cell-free DNA is contacted with an organic borane selected to successively bring about reduction, deamination, and decarboxylation of oxidized 5-methylcytosine residues such as 5-carboxylcytosine and 5-formylcytosine, resulting in DHU residues in place thereof. Following amplification, the treated cell-free DNA is sequenced, with the DHU residues read as thymine residues. Reaction mixtures, kits and additional methods are also provided, as are related methods for the epigenetic analysis of DNA, including cell-free DNA.

Methods are provided for the epigenetic analysis of cell-free DNA using organic boranes to convert oxidized 5-methylcytosine residues in the cell-free DNA to dihydrouracil (DHU) residues. Cell-free DNA is contacted with an organic borane selected to successively bring about reduction, deamination, and decarboxylation of oxidized 5-methylcytosine residues such as 5-carboxylcytosine and 5-formylcytosine, resulting in DHU residues in place thereof. Following amplification, the treated cell-free DNA is sequenced, with the DHU residues read as thymine residues. Reaction mixtures, kits and additional methods are also provided, as are related methods for the epigenetic analysis of DNA, including cell-free DNA.

The present invention relates to a process for the preparation of a compound of formula (I) said process comprising the steps of: a) reacting a compound of formula (II), with an acylating or a silylating agent to produce a compound of formula (III), wherein P.sup.1 and P.sup.2 are each independently a protecting group selected from R.sup.2—Si—R.sup.3R.sup.4, or R.sup.1CO—, wherein R.sup.1 is a group selected from C.sub.1-6alkyl or C.sub.3-6cycloalkyl, each group being optionally substituted by one or more substituents independently selected from fluoro or C.sub.1-4alkyl; R.sup.2, R.sup.3 and R.sup.4 are each independently a group selected from C.sub.1-6alkyl or phenyl, each group being optionally substituted by one or more substituents independently selected from fluoro or C.sub.1-4alkyl; b) reacting the compound of formula (III) in the presence of palladium acetate or a derivative thereof to produce compound of formula (IV); and c) reacting the compound of formula (IV) with a reducing agent to produce compound of formula (I). ##STR00001##

The present invention provides a system for evaporating a radioactive fluid, a method for the synthesis of a radiolabelled compound including this system, and a cassette for the synthesis of a radiolabelled compound comprising this system. The present invention provides advantages over known methods for evaporation of a radioactive fluid as it reduces drastically the amount of radioactive gaseous chemicals that are released in the hot cell. It is gentler and more secure compared to the known process and provides access to radiosyntheic processes that may not been acceptable for safety reasons related to release of volatile radioactive gases during evaporation. In addition, the process yields are higher because the radioactive volatiles are labelled intermediate species.

The present invention relates to a process for the preparation of a compound of formula (I) comprising the steps of a) reacting a compound of formula (II) with a silylating or an acylating agent to produce compound of formula (III), wherein P.sup.1 is a protecting group selected from R.sup.2—Si—R.sup.3R.sup.4 or R.sup.1CO—, R.sup.1 is a group selected from C.sub.1-6alkyl or C.sub.3-6cycloalkyl, each group being optionally substituted by one or more substituents independently selected from fluoro or C.sub.1-4alkyl; R.sup.2, R.sup.3 and R.sup.4 are each independently a group selected from C.sub.1-6alkyl or phenyl, each group being optionally substituted by one or more substituents independently selected from fluoro or C.sub.1-4alkyl; b) halogenation or sulfinylation of the compound of formula (III) to produce a compound of formula (IV); wherein X is halo, or —O—SO—R.sup.5, and R.sup.5 is a group selected from C.sub.6-10aryl or heteroaryl, each group being optionally substituted by one or more substituents independently selected from chloro or C.sub.1-4alkyl; c) dehalogenation or desulfinylation of the compound of formula (IV) to produce compound of formula (V); and d) reacting the compound of formula (V) with a reducing agent to produce compound of formula (I). ##STR00001##

A process for the preparation of 11-methylene steroids from di-keto steroids involves selective olefination of the ketone at position 11 of the di-keto steroids. The resulting 11-methylene steroid products can be used as intermediates in the preparation of the synthetic steroids, Etonogestrel and Desogestrel, as well as other pharmaceutically active agents.

The present invention relates generally to compositions and methods for treating cancer and hypercortisolism. Provided herein are substituted steroidal derivative compounds and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful for inhibition of glucocorticoid receptors. Furthermore, the subject compounds and compositions are useful for the treatment of cancer and hypercortisolism.