3350-42-3

Upstream product

• 15030-75-8 Z-Aib-ONp 
• 2491-20-5 L-alanine methyl ester hydrochloride 
• 10065-72-2 L-Alanine methyl ester 
• 210840-43-0 2-Benzyloxycarbonylamino-2-methyl-propionic acid 3,5-di-tert-butyl-4-hydroxy-phenyl ester 
• 15030-72-5 Z-Aib-OH 
• 367274-56-4 Z-Aib-F 
• 501-53-1 benzyl chloroformate 

Downstream Products

• 98735-75-2 ciBA-L-Ala> 
• 15030-86-1 [1-methyl-1-((S)-4-methyl-5-oxo-4,5-dihydro-oxazol-2-yl)-ethyl]-carbamic acid benzyl ester 
• 3350-45-6 N-(2-benzyloxycarbonylamino-2-methyl-propionyl)-L-alanine 
• 15028-53-2 Benzyloxycarbonyl-aminoisobutyryl-L-alanin 

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.

Impact of Dehydroamino Acids on the Structure and Stability of Incipient 310-Helical Peptides

A comparative study of the impact of small, medium-sized, and bulky α,β-dehydroamino acids (AAs) on the structure and stability of Balaram's incipient 310-helical peptide (1) is reported. Replacement of the N-terminal Aib residue of 1 with a AA

Investigation of permeation of theophylline through skin using selected piperazine-2,5-diones

Transdermal administration of drugs that penetrate, in this case directly into the blood circulation, has many advantages and is promising for many drugs thanks to its easy application and good patient compliance. (S)-8-Methyl-6,9-diazaspiro[4.5]decan-7,10-dione (alaptide), has been studied as a potential chemical permeation enhancer. Based on its structure, four selected piperazine-2,5-diones were synthesized by means of multi-step synthetic pathways. All the compounds were investigated on their ability to enhance the permeation of the model drug theophylline from the hydrophilic medium propylene glycol:water (1:1). In vitro experiments were performed using vertical Franz diffusion cells at constant temperature 34 ± 0.5 ?C and using full-thickness pig (Sus scrofa f. domestica) ear skin. Withdrawn samples were analyzed by RP-HPLC for determination of the permeated amount of theophylline. All the compounds were applied in ratio 1:10 (w/w) relative to the amount of theophylline. One hour after application, the permeated amount of theophylline from formulations with alaptide and (3S,6S)-3,6-dimethylpiperazine-2,5-dione, was ca. 15- and 12-fold higher, respectively, than from the formulation without the tested compounds. Despite the enhancement ratio of both enhancers in a steady state was ca. 2.3, the pseudo-enhancement ratio in the time range from 1 to 3 h was 4.4. These enhancement ratios indicate that the compounds are able to enhance the permeation of agents through the skin; however, the short-term application of both compound formulations seems to be more advantageous. In addition, the screening of the cytotoxicity of all the prepared compounds was performed using three cell lines, and the compounds did not show any significant toxic effect.

4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium Toluene-4-sulfonate (DMT/NMM/TsO?) Universal Coupling Reagent for Synthesis in Solution

4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium toluene-4-sulfonate (DMT/NMM/TsO?), a representative member of the inexpensive and environmentally-friendly N-triazinylammonium family of sulfonates, has been found to be a very effective coupling reagent for the synthesis of amides, esters and peptides in solution. This study confirms the usefulness of DMT/NMM/TsO? for peptide synthesis in solution, starting from Z-, Fmoc-, and Boc-protected substrates as well as unnatural building blocks. Peptide synthesis with DMT/NMM/TsO? produced high yields, with high crude product purity and low risk of racemization. In all cases, stoichiometric amounts of reagents were used and the standard synthetic procedure, without the need for time-consuming optimization stages or expensive chromatographic purification. DMT/NMM/TsO? was also found to be very useful for the synthesis of oligopeptides using a fragment coupling strategy.

Ethyl 2-cyano-2-(2-nitrobenzenesulfonyloxyimino)acetate (o -NosylOXY): A recyclable coupling reagent for racemization-free synthesis of peptide, amide, hydroxamate, and ester

Ubiquitousness of amide and ester functionality makes coupling reactions extremely important. Although numerous coupling reagents are available, methods of preparation of the common and efficient reagents are cumbersome. Those reagents generate a substantial amount of chemical waste and lack recyclability. Ethyl 2-cyano-2-(2-nitrobenzenesulfonyloxyimino)acetate (o-NosylOXY), the first member of a new generation of coupling reagents, produces byproducts that can be easily recovered and reused for the synthesis of the same reagent, making the method more environmentally friendly and cost-effective. The synthesis of amides, hydroxamates, peptides, and esters using this reagent is described. The synthesis of the difficult sequences, for example, the islet amyloid polypeptide (22-27) fragment (with a C-terminal Gly, H-Asn-Phe-Gly-Ala-Ile-Leu-Gly-NH 2) and acyl carrier protein (65-74) fragment (H-Val-Gln-Ala-Ala-Ile- Asp-Tyr-Ile-Asn-Gly-OH), following the solid-phase peptide synthesis (SPPS) protocol and Amyloid β (39-42) peptide (Boc-Val-Val-IIe-Ala-OMe), following solution-phase strategy is demonstrated. Remarkable improvement is noticed with respect to reaction time, yield, and retention of stereochemistry. A mechanistic investigation and recyclability are also described.

N-triazinylammonium tetrafluoroborates. A new generation of efficient coupling reagents useful for peptide synthesis

A new generation of triazine-based coupling reagents (TBCRs), designed according to the concept of "superactive esters", was obtained by treatment of 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium (DMTMM) chloride with lithium or silver tetrafluoroborate. The structure of 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium tetrafluoroborate was confirmed by X-ray diffraction. Activation of carboxylic acids by using this reagent proceeds via triazine "superactive ester". The coupling reagent was successfully used for the synthesis of Z-, Boc-, and Fmoc-protected dipeptides derived from natural and unnatural sterically hindered amino acids and for fragment condensation, in 80-100% yield and with high enantiomeric purity. The manual SPPS of the ACP(65-74) peptide fragment (H-Val-Gln-Ala-Ala- lle-Asp-Tyr-Ile-Asn-Gly-OH) proceeded significantly faster than with TBTU or HATU, as well as the automated SPPS of the same fragment gave a purer product than by using TBTU or PyBOP. The reagent was also demonstrated to be efficient in on-resin head-to-tail cyclization of constrained cyclopeptides, in SPPS synthesis of Aib peptides, and in the synthesis of esters from appropriate acids, alcohols, and phenols. The high efficiency and versatility of this new generation of TBCRs confirm, for the first time, the usefulness of the concept of "superactive esters" in rational design of the structure of coupling reagents.

P-toluenosulfonate salt of N-Methyl-N-(3,5-dimathoxy-2,4,6-triazinyl-1-)-morpholine and related compounds for use as condensing reagent in peptide synthesis

The invention refers to new quarternary N-(3,5-disubstituted-1,3,5-triazinyl-1)-ammonium salts of sulfonic acids, with formula 1, where R1 and R2 denote in total or independently a halogen atom, an alkyl group, a substituted alkyl gr

Oxidation-induced Acyl group transfer from hydroquinone esters to nucleophiles

Bivalent oxidation of 3,5-di-tert-butyl-hydroquinone monoesters leads to phenoxenium ions, which can transfer an acyl group to nucleophiles. Based on this principle, dipeptides, glyco-amino acids and N-sulfonyl-amino acids were synthesized from hydroquino

SYNTHESE VON 2-METHYLALANIN-PEPTIDEN, DIE pH-ABHAENGIGKEIT IHRER 13C-NMR-SPECTREN UND EINE NEUE METHODE ZUR AUSWERTUNG UEBER CS-DIAGRAMME

The uncommon amino-acid 2-methylalanine (α-aminoisobutiryc acid, Aib) was investigated by 13C-NMR.The chemical shifts of amino- or carboxy-protected derivates of Aib and of protected oligopeptides are discussed with respect to neighbouring groups and amino acids.The pH-dependence of the 13C-NMR spectra of Aib, Aib-Ala, Ala-Aib, Aib-Ala-Aib and Aib-Ala-Aib-Ala-Aib was studied.Using these examples, a new and advantageous method is demonstrated for the first time for the evaluation of NMR titration curves, which uses so-called chemical shift diagrams (CS diagrams).