DEVELOPMENT OF A METHOD FOR PRODUCING (-)-17-ALLYL-4,5Ά-EPOXY-3,14-DIHYDROXYMORPHINAN-6-ONE

Naloxone ((-)-17-allyl-4,5ά-epoxy-3,14-dihydroxymorphinan-6-one) is a pure opiate antagonist of a competitive type devoid of morphine-like activity and is widely used in clinical practice. The main raw material for the production of naloxone is thebaine, which is extracted from plant materials. This study presents a seven-step process for preparing naloxone with a yield of 35% (based on thebaine). Previously known methods of obtaining are characterized by the yield of the target product in terms of thebaine not higher than 20%. The greatest losses are recorded at the stage of obtaining oxycodone from thebaine and at the stage of O-demethylation of codeine. The use of formic acid in the hydrogenation process provides a more complete conversion of the intermediate product, and the use of boron tribromide in the environment of chloroalkanes at the stage of O-demethylation leads to the production of naloxone with a yield of more than 70%. A detailed study of the stages of obtaining oxycodone and noroxycodone allows to reduce the consumption of reagents and the time spent in the reactor, which is essential for reducing the cost of the final product. The proposed method is superior to those known in terms of productivity and economic efficiency and can be used for the development of industrial technology for the production of naloxone and its derivatives.

Synthesis and Structural Stability of α-Helical Gold(I)-Metallopeptidesy

The synthesis of hexa- and dodecapeptides functionalized with two Au(I)–phosphine complexes is reported. The high stability of the Au(I)–phosphine bond allowed orthogonal peptide-protecting-group chemistry, even when using hard Lewis acids like boron tribromide. This enabled the preparation of an Fmoc-protected lysine derivative carrying the Au(I) complex in a side chain, which was used in standard Fmoc-based solid-phase peptide synthesis protocols. Alanine and leucine repeats in the metallododecapeptide formed α-helical secondary structures in 2,2,2-trifluoroethanol–H2O and 1,1,1,3,3,3-hexafluoroisopropanol–H2O mixtures with high thermal stability, as shown by temperature-dependent CD spectroscopy studies.

Boron tribromide as a reagent for anti-Markovnikov addition of HBr to cyclopropanes

Anti-Markovnikov hydrobromination of cyclopropanes was achieved using boron tribromide and water as the bromine and proton sources, respectively.

An Expedient Synthesis of Ketocalix[6]arene Hexamethyl Ether

p-tert-Butylcalix[6]arene hexamethyl ether was oxidized in one step to the corresponding ketocalix[6]arene via photochemical bromination (100 W spot lamp) with NBS in a chloroform/water mixture. A pentamethyl ketocalix[6]arene derivative was obtained by reaction of the ketocalix[6]arene hexamethyl ether with boron tribromide dimethyl sulfide complex, and characterized by X-ray crystallography. In the presence of base, the compound undergoes an intramolecular nucleophilic aromatic substitution reaction.

Synthesis of Nepetoidin B

The first synthesis of nepetoidin B in an overall yield of 17% was achieved in two steps through Baeyer–Villiger oxidation of commercially available 1,5-bis(3,4-dimethoxyphenyl)-1,4-pentadien-3-one with oxone to produce the tetramethylated nepetoidin B, followed by demethylation using boron tribromide.

Boranes in Organic Chemistry 3. α-, β- and γ-Haloalkylboranes: The Perspective Vehicles for Organic Synthesis

<p>The methods of synthesis of α− and β−haloalkylboranes, including chloration of alkylboronic acid esters, additive bromation and chloration of esters of vinyl- and alkenylboronic acids, addition of bromine to trivinylborazines have been considered. The reactions of radical addition of polyhaloidmethanes to vinylboranes, α− and β−unsaturated boronic esters, B-vinyl-B-arylboronic esters, B-trivinyl-B-triarylborazines were discussed. The hydroboration of acetylenic halogenides of dicycloalkylboranes, which led to halocontaining derivatives of dialkylvinylborane was separately considered. The examples of hydroboration of halogenides of allyl and vinyl types are presented. The reaction of dienic synthesis, which takes place between vinylchloroboranes or vinylboronic esters and tetra- or hexachlorocyclopentadienes has been discussed. The reaction of alkenes and allenes with boron tribromide was described. The Markovnikov and non-Markovnikov hydrobromation of boron vinylderivatives has been envisaged. The approaches to the synthesis of perfluoroalkylboranes on the base of hydroboration of perfluoroalkenes have been discussed. The methods of the synthesis of boronates, containing halogetaryl substituents, have been performed. The reactions of hydroboration of halogenides of allylic and propargylic types by 9-borabicyclononane have been shown. The regio- and stereoselectivity of the reaction has been discussed. The examples of the synthesis of boranes of the norbornene type were presented. The reaction of boroallylilation of allyl- and propargylhalogenides leading to the derivatives of 3-bora-bicyclo[3,3,1]-nonane has been discussed. Some directions of using of haloidalkylboranes in the synthesis have been discussed. The examples of nucleophilic substitution leading to oxyalkyl- and azidoalkylboranes have been presented. The route of obtaining of alcohols from α−haloidalkylboranes has been shown. The general scheme of synthesis of α−aminoboronic acids was perfomed. The general approach to the synthesis of allenes on the base of hydroboration products of propargyl halogenides has been discussed. The schemes of synthesis of 1,4-disubstituted-1,2,3-butatrienes are presented. The wide using reaction of introducing of vinylic group into substituent, bonding with boron atom in molecules of dialkylvinylboranes, was discussed. The reactions of new C-C bonds formation, based on the action of iodine on the alkylvinylboronates leading to 1,3-dienes and alkylidencyclanes have been shown. Τhe route of the synthesis of cyclopropanes from β−haloidalkylboranes has been discussed.</p>