The present invention is directed to inhibitors of tyrosinase, pharmaceutical compositions comprising such tyrosinase inhibitors, and methods of making and using the same. Specifically, included in the present invention are compositions of matter comprised of at least one 2,4-dihydroxybenzene analog, which inhibit the activity of tyrosinase and which inhibit the overproduction of melanin.

The present invention relates to a process for preparing methyl methacrylate by direct oxidative esterification of methacrolein. Methyl methacrylate is used in large amounts for preparing polymers and copolymers with other polymerizable compounds. In addition, methyl methacrylate is an important synthesis unit for a variety of specialty esters based on methacrylic acid (MAA) which can be prepared by transesterification with the appropriate alcohol. There is consequently a great interest in very simple, economic and environmentally friendly processes for preparing this starting material. In particular the present invention relates to an optimized workup of the reactor effluent from the oxidative esterification of methacrolein by means of which process waste streams can be minimized and process water can be recycled in optimal fashion. The methacrylic acid generated in the process is also optimally recovered and isolated or converted into the commodity alkyl methacrylate. This process moreover has the advantage that fewer demands than described in the prior art are placed on plant apparatus configuration.

An object of the present invention is to provide a novel substance that has a high reactivity as a fluorinating agent, is effectively used in various fluorination reactions, and is safely handled even in air. As the solution for achieving this object, the present invention provides a complex obtained by reacting bromine trifluoride with at least one metal halide selected from the group consisting of halogenated metals and halogenated hydrogen metals in a nonpolar solvent. This complex serves as a fluorinating agent that provides excellent fluorination performance and that is stable in air.

Disclosed are new polycyclic carbogenic molecules and their methods of synthesis. The new polycyclic carbogenic molecules may be utilized in anti-cancer therapies. In particular, the polycyclic carbogenic molecules may be formulated as pharmaceutical compositions that comprise the small molecules, which compositions may be administered in methods of treating and/or preventing cell proliferative diseases and disorders such as cancer. The new polycyclic carbogenic molecules may be prepared from vinyl- or allyl-substituted cyclohexenone precursors via preparation of a silyl bis-enol ether intermediate.

The present invention is directed to inhibitors of tyrosinase, pharmaceutical compositions comprising such tyrosinase inhibitors, and methods of making and using the same. Specifically, included in the present invention are compositions of matter comprised of at least one 2,4-dihydroxybenzene analog, which inhibit the activity of tyrosinase and which inhibit the overproduction of melanin.

The present invention is directed to inhibitors of tyrosinase, pharmaceutical compositions comprising such tyrosinase inhibitors, and methods of making and using the same. Specifically, included in the present invention are compositions of matter comprised of at least one 2,4-dihydroxybenzene analog, which inhibit the activity of tyrosinase and which inhibit the overproduction of melanin.

The present disclosure provides ketone waxes, methods of forming ketone waxes, and compositions comprising ketone waxes. In at least one embodiment, a ketone wax is provided. The ketone wax includes about 50 wt % or greater C.sub.40-C.sub.90 ketone content; about 50 wt % or greater of the ketone wax has a boiling point of 961 F. or greater; and a paraffins content of less than about 10 wt %, as determined by 2-dimensional gas chromatography. In at least one embodiment, a method for forming a C.sub.40-C.sub.90 ketone wax includes exposing a feed stock to a basic catalyst under conditions suitable for coupling unsaturated carbon chains from the feed to form a composition including a ketone wax, oligomerizing the ketone wax to form a ketone wax having C.sub.40-C.sub.90 ketone wax, and distilling and/or extracting the oligomerized ketone wax to provide a C.sub.40-C.sub.90 ketone wax of the present disclosure.

An object of the present invention is to provide a novel substance that has a high reactivity as a fluorinating agent, is effectively used in various fluorination reactions, and is safely handled even in air. As the solution for achieving this object, the present invention provides a complex obtained by reacting bromine trifluoride with at least one metal halide selected from the group consisting of halogenated metals and halogenated hydrogen metals in a nonpolar solvent. This complex serves as a fluorinating agent that provides excellent fluorination performance and that is stable in air.

The invention relates to improved method of synthesis for Treprostinil comprising condensation reaction of the carbonyl compound having allyl, alkyl, crotyl or MEM-protected phenolic hydroxyl group, compound (4) with a hydroxyl-protected alkynol (5) to give the condensation product, compound (6). Subjecting compound (6) to oxidation, reduction, hydroxyl protection and carbonylation, cyclization reactions gave the tricyclic derivative (10). Further reactions comprising reduction, hydrogenation and deprotection of the phenolic and side-chain hydroxyl groups, wherein the sequence and choice of reagents was governed by protecting groups, gave the triol intermediate, compound (14). Cyanoalkylation at phenolic hydroxyl functionality and further hydrolysis yielded the prostacyclin compound, Treprostinil (1) and its pharmaceutically acceptable salts, having desired purity.

The invention relates to improved method of synthesis for Treprostinil comprising condensation reaction of the carbonyl compound having allyl, alkyl, crotyl or MEM-protected phenolic hydroxyl group, compound (4) with a hydroxyl-protected alkynol (5) to give the condensation product, compound (6). Subjecting compound (6) to oxidation, reduction, hydroxyl protection and carbonylation, cyclization reactions gave the tricyclic derivative (10). Further reactions comprising reduction, hydrogenation and deprotection of the phenolic and side-chain hydroxyl groups, wherein the sequence and choice of reagents was governed by protecting groups, gave the triol intermediate, compound (14). Cyanoalkylation at phenolic hydroxyl functionality and further hydrolysis yielded the prostacyclin compound, Treprostinil (1) and its pharmaceutically acceptable salts, having desired purity.