106928-49-8Relevant academic research and scientific papers
Constrained peptidomimetics reveal detailed geometric requirements of covalent prolyl oligopeptidase inhibitors
Lawandi, Janice,Toumieux, Sylvestre,Seyer, Valentine,Campbell, Philip,Thielges, Sabine,Juillerat-Jeanneret, Lucienne,Moitessier, Nicolas
experimental part, p. 6672 - 6684 (2010/04/28)
Prolyl oligopeptidases cleave peptides on the carboxy side of internal proline residues and their inhibition has potential in the treatment of human brain disorders. Using our docking program FITTED, we have designed a series of constrained covalent inhibitors, built from a series of bicyclic scaffolds, to study the optimal shape required for these small molecules. These structures bear nitrile functional groups that we predicted to covalently bind to the catalytic serine of the enzyme. Synthesis and biological assays using human brain-derived astrocytic cells and endothelial cells and human fibroblasts revealed that these compounds act as selective inhibitors of prolyl oligopeptidase activity compared to prolyl-dipeptidyl-aminopeptidase activity, are able to penetrate the cells and inhibit intracellular activities in intact living cells. This integrated computational and experimental study shed light on the binding mode of inhibitors in the enzyme active site and will guide the design of future drug-like molecules.
Enantioselective total syntheses of cyclopropane amino acids: Natural products and protein methanologs
Jimenez, Jose M.,Rife, Joan,Ortuno, Rosa M.
, p. 537 - 558 (2007/10/03)
The syntheses of (-)-allo-coronamic acid, (-)-allo-norcoronamic acid, (-)-(Z)-2,3-methanohomoserine, (-)-(Z)-2,3-methanomethionine, and (2S,3R)-Cbz-cyclo-Asp-OMe have been achieved in 45-68% overall yields from suitable intermediates derived from homochiral aminopentenoates which were obtained, in turn, from D-glyceraldehyde. The key synthetic step involves the quantitative and highly diastereoselective cyclopropanation of such precursors. The factors dealing with the control of stereoselectivity are highlighted and the main features in side-chain functionalization to the respective target molecules are discussed.
Synthesis of (Optically Active) Sulfur-Containing Trifunctional Amino Acids by Radical Addition to (Optically Active) Unsaturated Amino Acids
Broxterman, Quirinus B.,Kaptein, Bernard,Kamphuis, Johan,Schoemaker, Hans E.
, p. 6286 - 6294 (2007/10/02)
Sulfur-based radicals, generated from R-S-H-type precursors (R = alkyl, acyl) with AIBN, smoothly add to α-allylglycines protected at none, one, or both of the amino acid functions (NH2 and/or CO2H).Sulfur-containing trifunctional amino acids were obtained in good to excellent yields (64-100 percent).The solvent used for the reaction is critical.Optimal results were obtained when both the unsaturated amino acid and RSH dissolve completely in the medium (dioxane/water or methanol/water are good solvent systems).The scope of the reaction includes α-substituted α-allylglycine derivative and derivatives as well as β-substituted β-allyl-β-amino alcohols.In the case of optically active α-allylglycine derivatives, radical addition is accompanied by a small amount of racemization, the amount depending on the type of protection and R-S-H.The products are easily optically enriched by crystallization.Addition of sulfur-based radicals to α-allylglycine is believed to be an example of a general method for synthesizing optically active trifunctional amino acids from unsaturated amino acids.
Syntheses and Reactions of Silyl Carbamates. 1. Chemoselective Transformation of Amino Protecting Groups via tert-Butyldimethylsilyl Carbamates
Sakaitani, Masahiro,Ohfune, Yasufumi
, p. 870 - 876 (2007/10/02)
The N-tert-butyldimethylsilyloxycarbonyl group (silyl carbamate) was synthesized from commonly used amino protecting groups such as N-tert-butoxycarbonyl (Boc) and N-benzyloxycarbonyl (Z) by treatment with tert-butyldimethylsilyl trifluoromethanesulfonate/2,6-lutidine and tert-butyldimethylsilane/Pd(OAc)2, respectively.This novel species, upon activation with fluoride ion, reacts with a variety of electrophiles to give N-ester type compounds in high yield.For example, the conversion of N-t-Boc compounds into their corresponding N-Z compounds via a silyl carbamate was accomplished under these mild reaction conditions.
Tertiary-butyldimethylsilyl carbamate derivative and process for producing the same
-
, (2008/06/13)
A t-butyldimethylsilyl carbamate derivative and a process for producing the same are disclosed. Tertiary-butyldimethylsilyl carbamate derivatives having the following general formula (1) are intermediates for the production of a variety of carbamate ester
SYNTHESIS OF α-AMINO ACIDS WITH β,γ-UNSATURATED SIDE CHAINS
Castelhano, Arlindo L.,Horne, Stephen,Taylor, Gregg J.,Billedeau, Roland,Krantz, Allen
, p. 5451 - 5466 (2007/10/02)
α-Amino acids with allenyl, vinyl and acetylenic side chains can be synthesized using non-enolate based strategies.The ester enolate-Claisen rearrangement applied to propargylic esters of N-protected α-amino acids is of limited utility since only poor yields of allenic product are obtained with the N-Boc glycine esters, the system which give the most reproducible results.However, α-allenyl-α-amino acids that are fully functionalized on the α-carbon are available through the agency of 4-allenyl-2-phenyloxazolones 4 ( obtained from propargyl esters of N-benzoyl protected amino acids via cyclization and Claisen rearrangement ) provided that Meerwein's reagent is used to facilitate hydrolysis of the benzamide function in 5.A variety of α-substituted glycinates, including those with α-vinyl and α-acetylenic functions, can be prepared using a two step sequence involving condensation of the cationic glycine synthon 22 with various organomagnesium reagents, followed by hydrolysis.
SELECTIVE TRANSFORMATION OF N-t-BUTOXYCARBONYL GROUP INTO N-ALKOXYCARBONYL GROUP via N-CARBOXYLATE ION EQUIVALENT
Sakaitani, Masahiro,Ohfune, Yasufumi
, p. 5543 - 5546 (2007/10/02)
Reaction of a variety of N-t-butoxycarbonyl compounds with t-butyldimethylsilyl trifluoromethanesulfonate afforded the N-t-butyldimethylsilyloxycarbonyl compounds, chemoselectively, which upon treatment with an alkyl or aryl halide provided the corresponding N-alkoxy- or N-aryloxycarbonyl compounds, efficiently.
