Abstract: The present invention provides processes for the stereoselective synthesis of 6-alpha-amino morphinans. In particular, the invention provides processes for the reductive amination of 6-keto normorphinans by catalytic transfer hydrogenation.

Abstract: The present invention provides processes for the stereoselective synthesis of 6-alpha-amino N-substituted morphinans. In particular, the invention provides processes for the reductive amination of 6-keto N-substituted morphinans by catalytic hydrogen transfer.

Abstract: In certain embodiments, the invention relates to an implantable medical device that includes a body having an internal cavity. Receptor sites in the internal cavity may be adapted to repeatedly bind to, temporarily hold, and release an active agent. An opening may extend through the body and into the internal cavity to allow the active agent into and out of the internal cavity. This opening may be sized and shaped to prevent blood cells from entering the internal cavity through the opening while allowing the active agent to enter and/or exit the cavity via the opening. A polymeric structure may be located in the internal cavity. This polymeric structure may include artificial receptor site mimics for the active agent.

Abstract: In certain embodiments, the invention relates to an implantable medical device that includes a body having an internal cavity. Receptor sites in the internal cavity may be adapted to repeatedly bind to, temporarily hold, and release an active agent. An opening may extend through the body and into the internal cavity to allow the active agent into and out of the internal cavity. This opening may be sized and shaped to prevent blood cells from entering the internal cavity through the opening while allowing the active agent to enter and/or exit the cavity via the opening. A polymeric structure may be located in the internal cavity. This polymeric structure may include artificial receptor site mimics for the active agent.

Abstract: The present invention is directed to processes for the synthesis of morphinans. In particular, a process for cyclizing a ?,?-bicyclic ketone compound to form a nordihydrothebainone product using the Grewe cyclization reaction is improved by forming a reaction mixture comprising a ?,?-bicyclic ketone compound, a cyclizing acid and a water scavenging cyclization additive. In one embodiment, the Grewe transformation occurs in the presence of an acid anhydride as the cyclization additive. Further, the present invention is directed to processes for converting ?,?-bicyclic ketone compounds (e.g., by-products of the Grewe cyclization reaction) to ?,?-bicyclic ketone compounds, wherein the ?,?-bicyclic ketone compounds may be recovered to further undergo Grewe cyclization and form the nordihydrothebainone product.

Abstract: Novel opiate intermediate compositions and methods of synthesis that include changing the substitution pattern on the aromatic ring of the pre-Grewe intermediate are provided. The intermediates are morphinane derivatives of formula (10), wherein X is a F or Cl and R is selected from the group consisting of an H, alkyl, aryl, acyl, formyl, COR?, CONHR?, COOR, Bn(benzyl), alkyl(methyl), and sulfonamide SO2CH2COPh.

Abstract: An organized mobile multicomponent conjugate (OMMC) and method of using to enhance binding of weakly binding compounds to a target. A lamellar structure containing at least two binding compounds is assembled under conditions in which the binding compounds self-regulate in or on the lamellar structure, forming a cooperative ensemble that is capable of binding with enhanced affinity to a complementary affinity site on a target. Each binding compound is bound to the lamellar surface, and may be connected by a linker. The OMMC may contain an effector molecule, such as a diagnostic or therapeutic agent, for administration to a patent who is then diagnosed or treated using the effector molecule.

Abstract: An organized mobile multicomponent conjugate (OMMC) and method of using to enhance binding of weakly binding compounds to a target. A lamellar structure containing at least two binding compounds is assembled under conditions in which the binding compounds self-regulate in or on the lamellar structure, forming a cooperative ensemble that is capable of binding with enhanced affinity to a complementary affinity site on a target. Each binding compound is bound to the lamellar surface, and may be connected by a linker. The OMMC may contain an effector molecule, such as a diagnostic or therapeutic agent, for administration to a patient who is then diagnosed or treated using the effector molecule.

Abstract: The present invention provides (+)-morphinanium N-oxide compounds or pharmaceutically acceptable salts thereof. The invention also provides processes for producing (+)-morphinanium N-oxides or pharmaceutically acceptable salts thereof from the corresponding tertiary N-substituted (+)-morphinan compound or pharmaceutically acceptable salt thereof.

Abstract: The present invention provides (+)-morphinanium compounds comprising substituted 6-hydroxy or 6-amine groups. The invention also provides methods for inhibiting microglial activation by administering the compounds of the invention.

Abstract: The present invention provides (+)-morphinanium quaternary salts. The invention also provides processes for producing (+)-morphinanium quaternary salts from tertiary N-substituted (+)-morphinan compounds.

Abstract: The present invention is directed to the reduction of an N-imine moiety or a hemiaminal moiety of a morphinan in the presence of a ruthenium, rhodium, or iridium asymmetric catalyst and a hydrogen source.

Abstract: An organized mobile multicomponent conjugate (OMMC) and method of using to enhance binding of weakly binding compounds to a target. A lamellar structure containing at least two binding compounds is assembled under conditions in which the binding compounds self-regulate in or on the lamellar structure, forming a cooperative ensemble that is capable of binding with enhanced affinity to a complementary affinity site on a target. Each binding compound is bound to the lamellar surface, and may be connected by a linker. The OMMC may contain an effector molecule, such as a diagnostic or therapeutic agent, for administration to a patent who is then diagnosed or treated using the effector molecule.

Abstract: The present invention is directed to the preparation of 6-keto morphinans.

Abstract: An improved method for the preparation of oxymorphone from oripavine is provided. Oripavine is oxidized to form 14-hydroxymorphinone after which the oxidation reaction is quenched to prevent the formation of 1-1?-dimer side products. The 14-hydroxymorphinone is then reduced, typically by catalytic hydrogenation to form oxymorphone. The inventive method disclosed is further applicable to the production of morphinan derivatives.

Abstract: The present invention is generally directed to a process for the preparation of a ketomorphinan comprising maintaining a ketone group as unprotected and performing reductive amination using a hydrogen source and a catalyst.

Abstract: The present invention is directed to the preparation of 6-hydroxy morphinans having formula (II) or N-alkylated 6-hydroxy morphinans having formula (III).

Abstract: In certain embodiments, the invention relates to an implantable medical device that includes a body having an internal cavity. Receptor sites in the internal cavity may be adapted to repeatedly bind to, temporarily hold, and release an active agent. An opening may extend through the body and into the internal cavity to allow the active agent into and out of the internal cavity. This opening may be sized and shaped to prevent blood cells from entering the internal cavity through the opening while allowing the active agent to enter and/or exit the cavity via the opening. A polymeric structure may be located in the internal cavity. This polymeric structure may include artificial receptor site mimics for the active agent.

Abstract: The present invention is directed to processes for the synthesis of morphinans. In particular, a process for coupling a carboxylic acid compound with an amine compound to form an amide product that can then be isolated or the crude amide product can be cyclized to form a 3,4-dihydroisoquinoline. In one embodiment, the carboxylic acid contains a phenol moiety protected with a labile protecting group. The protected phenol reduces reaction times, simplifies work-up of the product, and reduces the amount of cyclizing agent, POCl3 that is necessary to form the 3,4-dihydroisoquinoline.

Abstract: The present invention provides processes for the synthesis of substituted berbine compounds. Also provided are intermediates used in the synthesis of substituted berbine compounds.