213315-70-9

Upstream product

• 176962-19-9 (S)-1-(1'-methyl)-ethyl-3,3-dibromo-N-(t-butoxycarbonyl)-2-propenamine 
• 87694-52-8 tert-butyl (S)-1-(N-methoxy-N-methylcarbamoyl)-2-methylpropylcarbamate 
• 90965-06-3 dimethyl 1-(1-diazo-2-oxopropyl)phosphonate 
• 293329-55-2 tert-butyl 1-(methoxy(methyl)amino)-3-methyl-1-oxobutan-2-ylcarbamate 
• 24424-99-5 di-tert-butyl dicarbonate 
• 4202-14-6 dimethyl (2-oxopropyl)phosphonate 
• 106391-88-2 (2R)-2-[(tert-butoxycarbonyl)amino]-3-methylbutylaldehyde 
• 4301-14-8 acetylenemagnesium bromide 
• 79069-51-5 (S)-N-tert-butoxycarbonylvalinal 
• 13734-41-3 t-Boc-L-valine 
• 56438-76-7 3-benzoyloxy-4-methyl-pent-1-yne 
• 16169-84-9 (RS)-4-methyl-pent-1-yn-3-acetoxy 
• 565-68-4 4-methylpent-1-yn-3-ol 

Relevant academic research and scientific papers

Synthesis of homochiral propargyl amines from W-(Boc)-tetrahy dro-2#-l,3-oxazines

The functionalisation of homochiral N-(Boc)-tetrahydro-2//-l,3-oxazines with the Grignard reagent of (trimethylsilyl)acetylene under Lewis acidic conditions is described. This leads directly to homochiral propargyl amines in good yields, under mild condit

1,5-Disubstituted 1,2,3-Triazole-Containing Peptidotriazolamers: Design Principles for a Class of Versatile Peptidomimetics

Peptidotriazolamers are hybrid foldamers combining features of peptides and triazolamers—repetitive peptidomimetic structures with triazoles replacing peptide bonds. We report on the synthesis of a new class of peptidomimetics, containing 1,5-disubstituted 1,2,3-triazoles in an alternating fashion with amide bonds and the analysis of their conformation in solid state and solution. Homo- or heterochiral peptidotriazolamers were obtained from enantiomerically pure propargylamines with stereogenic centers in the propargylic position and α-azido esters by ruthenium-catalyzed azide–alkyne cycloaddition (RuAAC) under microwave conditions in high yields. With such building blocks the peptidotriazolamers are readily available by solution phase synthesis. While the conformation of the homochiral peptidotriazolamer Boc-Ala[5Tz]Phe-Val[5Tz]Ala-Leu[5Tz]Val-OBzl resembles that of a β VIa1 turn, the heterochiral peptidotriazolamer Boc-d-Ala[5Tz]Phe-d-Val[5Tz]Ala-d-Leu[5Tz]Val-OBzl adopts a polyproline-like repetitive structure.

Enzymatic Macrocyclization of 1,2,3-Triazole Peptide Mimetics

The macrocyclization of linear peptides is very often accompanied by significant improvements in their stability and biological activity. Many strategies are available for their chemical macrocyclization, however, enzyme-mediated methods remain of great interest in terms of synthetic utility. To date, known macrocyclization enzymes have been shown to be active on both peptide and protein substrates. Here we show that the macrocyclization enzyme of the cyanobactin family, PatGmac, is capable of macrocyclizing substrates with one, two, or three 1,4-substituted 1,2,3-triazole moieties. The introduction of non-peptidic scaffolds into macrocycles is highly desirable in tuning the activity and physical properties of peptidic macrocycles. We have isolated and fully characterized nine non-natural triazole-containing cyclic peptides, a further ten molecules are also synthesized. PatGmac has now been shown to be an effective and versatile tool for the ring closure by peptide bond formation.

Cu(I)-catalyzed synthesis of dihydropyrimidin-4-ones toward the preparation of β- And β3-amino acid analogues

A copper(I)-catalyzed synthesis of substituted dihydropyrimidin-4-ones from propargyl amides via the formation of ketenimine intermediate has been successfully developed; the synthesis afforded good isolated yields (80-95%). The mild reaction conditions at room temperature allow the reaction to proceed to completion in a few hours without altering the stereochemistry. Further, by involving a variety of reactive nucleophiles, the obtained substituted dihydropyrimidin-4-ones were elegantly transformed into the corresponding β- and β3-amino acid analogues.

Radiolabeled antagonistic bombesin peptidomimetics for tumor targeting

The replacement of amide bonds in the backbone of peptides by proteolytically stable 1,2,3-triazole isosteres can provide novel peptidomimetics with promising properties for the development of tumor-targeting radiopeptides. On the basis of our previous work with radiolabeled agonistic bombesin (BBN) derivatives of the sequence [Nle14]BBN(7-14), we substituted selected amide bonds of the structurally closely related antagonistic peptide analog JMV594. With the exception of the C-terminal modification, amide-to-triazole substitutions tolerated by [Nle 14]BBN(7-14) without loss of biological function led to abolished receptor affinity in the case of JMV594. These findings provide an additional piece of evidence for the currently disputed differences in the modes of action of agonistic and antagonistic gastrin-releasing peptide receptor (GRPR)-targeting radiopeptides.

1,2,3-Triazoles as amide bond mimics: Triazole scan yields protease-resistant peptidomimetics for tumor targeting

The triazole makes the difference: Replacement of amide bonds in the backbone of peptides by 1,4-disubstituted 1,2,3-triazole isosteres affords peptidomimetics with retained receptor affinity and cell-internalization properties, enhanced proteolytic stability, and improved tumor-targeting capabilities. Copyright

Enantioselective copper-catalysed propargylic substitution: Synthetic scope study and application in formal total syntheses of (+)-anisomycin and (-)-cytoxazone

A copper catalyst with a chiral pyridine-2,6-bisoxazoline (pybox) ligand was used to convert a variety of propargylic esters with different side chains (R=Ar, Bn, alkyl) into their amine counterparts in very high yields and with good enantioselectivities (up to 90% enantiomeric excess (ee)). Different amine nucleophiles were applied in the reactions and the highest enantioselectivities were obtained for aniline and its analogues. Interestingly, some carbon nucleophiles could also be used and with indoles excellent ee values were obtained (up to 98% ee). The versatility of the propargylic amines obtained was demonstrated by their further elaboration to formal total syntheses of the antibiotic (+)-anisomycin and the cytokine modulator (-)-cytoxazone. Copyright

A reasonably stereospecific multistep conversion of Boc-protected α-amino acids to Phth-protected β3-amino acids

A method for the synthesis of β3-amino acids starting from α-amino acids is described. This conversion can be effected by an eight-step procedure which involves the transformation of the carboxylic group into an alkyne followed by a selenium-mediated conversion of the carbon-carbon triple bond to a Se-phenyl selenocarboxylate intermediate. The reactive Se-phenyl selenocarboxylate intermediates can be trapped with water, alcohols or the amine of an amino acid derivative to give β3-amino acids, β3-amino esters or mixed peptides, respectively. The whole transformations of the carboxylic group into an alkyne and of the alkyne group into β3-amino acids may not require purification of the intermediate products but a work-up and isolation procedure of crude materials.

ALPHA2B AND ALPHA2C AGONISTS

Described herein are compounds that can be useful as bioactive agents. More specifically, the compounds described herein can be useful as both α2B and α2C adrenergic agonists. Methods of synthesis and administration of the compounds are also disclosed.

A practical gold-catalyzed route to 4-substituted oxazolidin-2-ones from N-Boc propargylamines

Au1-catalyzed cyclization of N-Boc propargylamines into 4-alkylidene oxazolidin-2-ones is described. This modular approach provides access to a variety of nonproteogenic 4-substituted oxazolidinones that are important in asymmetric synthesis an