Cbz-protected Amines Research Articles

Antibacterial Conjugates of Kanamycin A with Vancomycin and Eremomycin: Biological Activity and a New MS-Fragmentation Pattern of Cbz-Protected Amines.

A significant increase of microbial resistance to glycopeptides (especially vancomycin-resistant enterococci and Staphylococcus aureus) prompted researchers to design new semisynthetic glycopeptide derivatives, such as dual-action antibiotics that contain a glycopeptide molecule and an antibacterial agent of a different class. We synthesized novel dimeric conjugates of kanamycin A with glycopeptide antibiotics, vancomycin and eremomycin. Using tandem mass spectrometry fragmentation, UV, IR, and NMR spectral data, it was unequivocally proven that the glycopeptide is attached to the kanamycin A molecule at the position 1 of 2-deoxy-D-streptamine. New MS fragmentation patterns for N-Cbz-protected aminoglycosides were discovered. It was found that the resulting conjugates are active against Gram-positive bacteria, and some are active against vancomycin-resistant strains. Conjugates of two different classes can serve as dual-target antimicrobial candidates for further investigation and improvement.

On-DNA Transfer Hydrogenolysis and Hydrogenation for the Synthesis of DNA-Encoded Chemical Libraries.

DNA-encoded libraries (DELs) are an increasingly popular approach to finding small molecule ligands for proteins. Many DEL synthesis protocols hinge on sequential additions of monomers using split-pool combinatorial methods. Therefore, compatible protecting group strategies that allow the unmasking of reactive functionality (e. g. amines and alcohols) prior to monomer coupling, or the removal of less desirable functionality (e. g., alkenes and alkynes) are highly desirable. Hydrogenation/hydrogenolysis procedures would achieve these ends but have not been amenable to DEL chemistry. We report a catalytic hydrogen transfer reaction using Pd/C, HCONH4 and the micelle-forming surfactant, TPGS-750-M, which gives highly efficient conversions for hydrogenolysis of Cbz-protected amines and benzyl protected alcohols and hydrogenation of nitros, halides, nitriles, aldehydes, alkenes and alkynes. Application to multicycle synthesis of an encoded compound was fully compatible with DNA-amplification and sequencing, demonstrating its applicability to DEL synthesis. This method will enable synthetic DEL sequences using orthogonal protecting groups.

On-DNA Transfer Hydrogenolysis and Hydrogenation for the Synthesis of DNA-Encoded Chemical Libraries.

DNA‐encoded libraries (DELs) are an increasingly popular approach to finding small molecule ligands for proteins. Many DEL synthesis protocols hinge on sequential additions of monomers using split‐pool combinatorial methods. Therefore, compatible protecting group strategies that allow the unmasking of reactive functionality (e. g. amines and alcohols) prior to monomer coupling, or the removal of less desirable functionality (e. g., alkenes and alkynes) are highly desirable. Hydrogenation/hydrogenolysis procedures would achieve these ends but have not been amenable to DEL chemistry. We report a catalytic hydrogen transfer reaction using Pd/C, HCONH4 and the micelle‐forming surfactant, TPGS‐750‐M, which gives highly efficient conversions for hydrogenolysis of Cbz‐protected amines and benzyl protected alcohols and hydrogenation of nitros, halides, nitriles, aldehydes, alkenes and alkynes. Application to multicycle synthesis of an encoded compound was fully compatible with DNA‐amplification and sequencing, demonstrating its applicability to DEL synthesis. This method will enable synthetic DEL sequences using orthogonal protecting groups.

Comparison between Conventional and Nonconventional Methods for the Synthesis of Some 2-Oxazolidinone Derivatives and Preliminary Investigation of Their Inhibitory Activity Against Certain Protein Kinases

A series of propargyl and allyl carbamates were prepared directly from propargyl and allyl alcohols and phenyl or cyclohexyl isocyanate or indirectly by generating the isocyanates in situ from the corresponding Cbz-protected amines. The obtained carbamates underwent intramolecular nucleophilic cyclization in presence of cesium hydroxide monohydrate as a base catalyst under conventional and ultrasonic irradiation conditions to give the corresponding substituted 4-(benzylidene)methylidene-2-oxazolidinones in good to excellent yields. The use of ultrasonic irradiation provided remarkably improved yield of the cyclization products and significant shortening of the reaction time. In some cases the reaction was highly stereoselective, and (Z)-4-benzylideneoxazolidinones were formed as a single stereoisomer. A series of biological tests were performed to evaluate the inhibitory potential of all synthesized compounds against some protein kinases.

Facile one-pot synthesis of unsymmetrical ureas, carbamates, and thiocarbamates from Cbz-protected amines.

A novel one-pot synthesis of unsymmetrical ureas, carbamates and thiocarbamates from Cbz-protected amines has been developed. In the presence of 2-chloropyridine and trifluoromethanesulfonyl anhydride, isocyanates are generated in situ, which facilitate rapid reaction with amines, alcohols, and thiols to afford the corresponding ureas, carbamates and thiocarbamates in high yields.

Direct Amidation of N-Boc- and N-Cbz-Protected Amines via Rhodium-Catalyzed Coupling of Arylboroxines and Carbamates.

N-Boc- and N-Cbz-protected amines are directly converted into amides by a novel rhodium-catalyzed coupling of arylboroxines and carbamates, replacing the traditional two-step deprotection-condensation sequence. Both protected anilines and aliphatic amines are efficiently transformed into a wide variety of secondary benzamides, including sterically hindered and electron-deficient amides, as well as in the presence of acid-labile and reducible functional groups.

Gold-Catalyzed, SN1-Type Reaction of Alcohols to Afford Ethers and Cbz-Protected Amines

The use of a gold-catalyzed, microwave protocol to activate alcohols through an intermolecular, SN1-type reaction to directly form unsymmetrical ethers and N-benzyloxy carbamate- (Cbz) protected amines is reported. Results have shown this reaction to be highly reproducible and tolerant of moisture, and moderate to high product yields (53–99%) were obtained. Significantly, the intermolecular catalytic amination of alcohols to directly afford Cbz-protected amines is heretofore unprecedented using gold catalysis.

Efficient and selective cleavage of the t-butoxycarbonyl group from di- t-butylimidodicarbonate using catalytic bismuth(III) bromide in acetonitrile

Di- t-butylimidodicarbonates can be chemoselectively and efficiently deprotected to the corresponding mono-BOC-protected amines in high yields using a catalytic amount of bismuth(III) bromide in acetonitrile at room temperature. This method is mild and compatible with the presence of a wide range of functional and other protecting groups in the substrates, such as TBDMS, MOM and mono-BOC or Cbz-protected amines, etc. The method has advantages of ease of operation and use of nontoxic and inexpensive catalyst.

A Novel, One‐Step Method for the Conversion of Primary Alcohols into Carbamate‐Protected Amines.

AbstractFor Abstract see ChemInform Abstract in Full Text.

A novel, one-step method for the conversion of primary alcohols into carbamate-protected amines

A novel process for the one-step conversion of primary alcohols into carbamate-protected amines has been developed using a modified Burgess reagent. Although this letter mainly focuses on the conversion of alcohols into the corresponding Cbz-protected amines, the potential for extending this process to a wide range of carbamates has also been demonstrated. A detailed catalytic cycle has been proposed. While exploring the scope of this new reagent, an N-aryl piperidine to an N-aryl pyrrolidine rearrangement has been observed and rationalized.

Selective cleavage of Cbz-protected amines.

Under conditions of catalytic Ni(0) and in most cases just over 1 equiv of Me(2)NH.BH(3)/K(2)CO(3) or Cs(2)CO(3), a Cbz-protected nitrogen, which is part of a heteroaromatic ring, can be chemospecifically cleaved without affecting a Cbz group on an originally basic amine. [reaction: see text]