6671-25-6

Upstream product

• 13257-67-5 2-amino-2-methylpropionic acid methyl ester 
• 15030-72-5 Z-Aib-OH 
• 15030-73-6 Z-Aib-oPiv 
• 15028-41-8 methyl 2-aminoisobutyrate hydrochloride 
• 67-56-1 methanol 
• 79775-03-4 2-<2-(Benzyloxycarboxamido)-2-methylpropionamido>-2-methylpropionsaeure 
• 39608-52-1 benzyl carbonochloridate 
• 367274-56-4 Z-Aib-F 
• 501-53-1 benzyl chloroformate 
• 15030-74-7 (Z-Aib)2O 

Downstream Products

• 79775-03-4 2-<2-(Benzyloxycarboxamido)-2-methylpropionamido>-2-methylpropionsaeure 
• 128422-23-1 Z-Leu-Aib-Pro-Val-Aib-Aib-OH 
• 132363-02-1 Z-Val-Aib-Aib-OMe 
• 71890-86-3 Z-Pro-Val-Aib-Aib-OMe 
• 172992-17-5 Z-Aib-Pro-Val-Aib-Aib-OMe 
• 172992-18-6 Z-Leu-Aib-Pro-Val-Aib-Aib-OMe 
• 71890-87-4 N-phenylmethoxycarbonyl-L-prolyl-L-valyl-2-methylalanyl-2-methylalanine 
• 132329-81-8 Z-Ala-Aib-Aib-OMe 
• 132329-82-9 Z-Ala-Ala-Ala-Aib-Aib-OMe 
• 96235-56-2 L-Pro-L-Val-Aib-Aib-L-Gln-L-Gln-L-Phl 
• 132329-83-0 Z-Pro-Val-Aib-Aib-Gln-Gln-Pheol 
• 4512-46-3 3,3,6,6-tetramethyl-2,5-dioxopiperazine 
• 87208-84-2 H₂N-(Aib)2-OMe 
• 109335-02-6 N,N-dibenzyl-O-tert-butyltyrosyl-α-aminoisobutyryl-α-aminoisobutyrylmelphalanylleucine tert-butyl ester 

Relevant academic research and scientific papers

Metal-free approach for hindered amide-bond formation with hypervalent iodine(iii) reagents: application to hindered peptide synthesis

A new bio-inspired approach is reported for amide and peptide synthesis using α-amino esters that possess a potential activating group (PAG) at the ester residue. To activate the ester functionality under mild metal-free conditions, we exploited the facile dearomatization of phenols with hypervalent iodine(iii) reagents. Using a pyridine-hydrogen fluoride complex, highly reactive acyl fluoride intermediates can be successfully generated, thereby allowing for the smooth formation of sterically hindered amides and peptides from bulky amines and α-amino esters, respectively.

Peptide Mechanosynthesis by Direct Coupling of N-Protected α-Amino Acids with Amino Esters

In view of developing alternatives to classical peptide synthesis strategies that suffer from low efficacy and negative environmental impact, the reactivity of N-protected α-amino acids, amino esters, and N-ethyl-N′-(3-dimethylaminopropyl)carbodiimide was

Conformation-specific spectroscopy of capped, gas-phase Aib oligomers: Tests of the Aib residue as a 310-helix former

The conformational preferences of a series of capped peptides containing the helicogenic amino acid aminoisobutyric acid (Aib) (Z-Aib-OH, Z-(Aib)2-OMe, and Z-(Aib)4-OMe) are studied in the gas phase under expansion-cooled conditions. Aib oligomers are known to form 310-helical secondary structures in solution and in the solid phase. However, in the gas phase, accumulation of a macrodipole as the helix grows could inhibit helix stabilization. Implementing single-conformation IR spectroscopy in the NH stretch region, Z-Aib-OH and Z-(Aib)2-OMe are both observed to have minor conformations that exhibit dihedral angles consistent with the 310-helical portion of the Ramachandran map (φ, ψ = -57°, -30°), even though they lack sufficient backbone length to form 10-membered rings which are a hallmark of the developed 310-helix. For Z-(Aib)4-OMe three conformers are observed in the gas phase. Single-conformation infrared spectroscopy in both the NH stretch (Amide A) and CO stretch (Amide I) regions identifies the main conformer as an incipient 310-helix, having two free NH groups and two C10 H-bonded NH groups, labeled an F-F-10-10 structure, with a calculated dipole moment of 13.7 D. A second minor conformer has an infrared spectrum characteristic of an F-F-10-7 structure in which the third and fourth Aib residues have φ, ψ = 75°, -74° and -52°, 143°, Ramachandran angles which fall outside of the typical range for 310-helices, and a dipole moment that shrinks to 5.4 D. These results show Aib to be a 310-helix former in the gas phase at the earliest stages of oligomer growth.

The effect of counterion and tertiary amine on the efficiency of N-triazinylammonium sulfonates in solution and solid-phase peptide synthesis

A collection of N-triazinylammonium sulfonates, designed according to the concept of "superactive esters", was obtained by treatment of ammonium sulfonates with 2-chloro-4,6-dimethoxy-1,3,5-triazine. The structure of the tertiary amine as well as sulfonate anion influenced their reactivity and stability in N,N-dimethylformamide (DMF) solution. The reagents were successfully used in solution- and solid-phase synthesis of Z-, Boc-, and Fmoc-protected peptides containing natural and unnatural sterically hindered amino acids as well as in [2+1] fragment condensation approaches, yielding the final products in 80-100% yield and high optical purity. In manual SPPS of the [Aib]2[Aib]4-enkephalin analogue and the ACP(65-74) peptide fragment VQAAIDYINEG, several sulfonates yielded peptides significantly faster than TBTU or HATU. Comparative analyses demonstrated that 4-(4,6-di-methoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium 4-toluenesulfonate was the most versatile reagent in a wide range of coupling procedures.

Synthesis of cyclopentapeptides with three to five Aib units

Four new Aib-containing cyclopentapeptides have been synthesized by cyclization of the corresponding linear pentapeptides using the diethyl phosphorocyanidate (DEPC)/EtN(iPr)2 method. The linear precursors were prepared via the 'azirine/oxazolo

Bis(4,6-dimethoxy-1,3,5-triazin-2-yl) ether as coupling reagent for peptide synthesis

Bis(4,6-dimethoxy-1,3,5-triazin-2-yl) ether (4) was prepared by treatment of 2-hydroxy-4,6-dimethoxy-1,3,5-triazine with 2-chloro-4,6-dimethoxy-1,3,5- triazine in 61% yield. Ether 4, isoelectronic with pyrocarbonates, was found capable to activate carboxylic acids in the presence of 1,4-diazabicyclo[2.2.2] octane (DABCO) to yield, under mild reaction conditions, superactive triazine esters. Versatility of this new coupling reagent was confirmed by condensation of lipophilic and sterically hindered carboxylic acids with amines in 71-98% yield, and by synthesis of peptides, including those containing Aib-Aib sequence, in solution with high yield and high enantiomeric purity. Copyright

N-lipidated oligopeptides immobilized on cellulose as new type of organocatalysts

A library of supramolecular structures formed by self-organization of N-lipidated tripeptides, dipeptides and Nacylated amino acids attached to cellulose according to the TASP concept via aminophenylamino-1,3,5-triazine was synthesized and the catalytic a

Synthesis of peptides employing protected-amino acid halides mediated by commercial anion exchange resin

Coupling of protected-amino acid halides (chloride, fluoride) mediated by commercial anion exchange resin for the solution phase synthesis of peptides is described. The reaction was carried out in an organic medium, circumventing the use of an organic base or an inorganic base. The coupling is fast, clean and racemization free. The anion exchange resin functions as a solid-phase basic scavenger, soaking up the HCl produced and allowing the amine to react. The method is extended for the coupling of sterically hindered α,α,- dialkylamino acids. Graphical Abstract: [Figure not available: see fulltext.]

4-(4,6-Di[2,2,2-trifluoroethoxy]-1,3,5-triazin-2-yl)-4-methylomorpholinium tetrafluoroborate. Triazine-based coupling reagents designed for coupling sterically hindered substrates

4-(4,6-Di[2,2,2-trifluoroethoxy]-1,3,5-triazin-2-yl)-4-methylomorpholinium tetrafluoroborate (DFET/NMM/BF4) was prepared and used as a reagent for coupling sterically hindered substrates. The formation of the appropriate triazine "superactive" ester in a reaction of DFET/NMM/BF4 with carboxylic acids was confirmed. The efficiency of the reagent has been studied in the synthesis of Leu-enkephaline pentapeptide carried out on a Fmoc-RinkAmide-AM-PS resin, by systematically modifying the -Gly-Gly- fragment for N-methyl or α,α-disubstituted residues and compared with the efficiency of classic aminium salt 2-(1H-benzotriazole-1-yl)-1,1,3,3- tetramethyluronium tetrafluoroborate (TBTU) under a variety of reaction conditions. In syntheses of Aib-Aib (Aib: α-aminoisobutyric acid), MeVal-MeVal, and MeLeu-MeLeu, the considerably superior performance of enkephaline analogues was obtained for DFET/NMM/BF4 relative to TBTU, regardless of reaction conditions. Analysis of the couplings involving triazine reagent suggests that factors controlling efficiency of coupling sterically hindered substrates are the structure of the leaving group permitting formation of the cyclic intermediate or cyclic transition state and the absence of strongly solvating solvents. It has to be considered as highly probable that the absence of strongly solvating milieu favors cyclic intermediates or the cyclic transition state. Arrangement of both components into the cyclic intermediate or cyclic transition state by accumulation of the geminal (vicinal) substituents effect (known as the Thorpe-Ingold effect) would compensate retardation of the coupling process caused by steric hindrance.

PS-IIDQ: a supported coupling reagent for efficient and general amide bond formation

Polystyrene-IIDQ, a polymer-supported coupling reagent, was synthesized in three steps from Merrifield resin in 86% overall conversion. This reagent efficiently coupled carboxylic acids to amines in good yields and high purities, required no pre-activation step, and was tolerant of the order of reagent addition. PS-IIDQ was observed to be more efficient than polymer-supported carbodiimides (PS-EDC and PS-DCC) and gave higher yields than HATU for general amide bond formation, including the coupling of anilines and hindered substrates. When evaluated with five carboxylic acids and nine amines (including anilines and secondary amines) PS-IIDQ gave an average isolated yield of 73%.