94885-52-6

Upstream product

• 98-79-3 L-Pyroglutamic acid 
• 100-51-6 benzyl alcohol 
• 100-44-7 benzyl chloride 
• 113400-36-5 benzyl (2S)-N-tert-butoxycarbonyl-5-oxoprolinate 
• 71389-33-8 dibenzyl (2S)-5-oxotetrahydro-1H-pyrrole-1,2-dicarboxylate 
• 103301-78-6 1-benzyl-5-oxo-pyrrolidine-2-carboxylic acid methyl ester 
• 18087-65-5 1-Benzyl-4,5-dichlor-1H-pyrrol-2-carbonsaeure-methylester 
• 60555-57-9 benzyl 5-oxopyrrolidine-2-carboxylate 
• 1468-39-9 Isovaleric anhydride 
• 100-39-0 benzyl bromide 

Downstream Products

• 106116-09-0 L-5-Oxo-1-(trimethylsilyl)prolin-benzylester 
• 113400-36-5 benzyl (2S)-N-tert-butoxycarbonyl-5-oxoprolinate 
• 71389-33-8 dibenzyl (2S)-5-oxotetrahydro-1H-pyrrole-1,2-dicarboxylate 
• 202918-12-5 (S)-1-(tert-Butyl-dimethyl-silanyl)-5-oxo-pyrrolidine-2-carboxylic acid benzyl ester 
• 363139-40-6 Boc-L-Ala-L-pGlu-OBn 
• 454228-34-3 Boc-(L-pGlu)2-OBzl 
• 454228-37-6 Boc-(L-pGlu)3-OBzl 
• 454228-40-1 Boc-(L-pGlu)4-OBzl 
• 504438-61-3 Boc-L-Val-L-pGlu-OBn 
• 86124-58-5 benzyl 3-(5-oxo-1-phenyl-2-thioxo-imidazolidin-4-yl)propanoate 
• 331949-29-2 benzyl (2S)-N-tert-butoxycarbonyl-5-hydroxypyrrolidine-2-carboxylate 
• 331949-31-6 benzyl (2S)-N-tert-butoxycarbonyl-5-methoxypyrrolidine-2-carboxylate 
• 863660-29-1 benzyl (2S)-N-tert-butoxycarbonyl-5-allylpyrrolidine-2-carboxylate 
• 372187-50-3 (2R,5R)-5-Allyl-2-((1S,2R)-2-tert-butoxycarbonylamino-1,3-dihydroxy-propyl)-pyrrolidine-1,2-dicarboxylic acid 2-benzyl ester 1-methyl ester 

Relevant academic research and scientific papers

Enantiopure 5-CF3-Proline: Synthesis, Incorporation in Peptides, and Tuning of the Peptide Bond Geometry

The straightforward synthesis of enantiopure 5-(R)-and 5-(S)-trifluoromethylproline is reported. The key steps are a Ruppert-Prakash reagent addition on l-pyroglutamic esters followed by an elimination reaction and a selective reduction. The solution-phase and solid-phase incorporation of this unprotected enantiopure fluorinated amino acid in a short peptide chain was demonstrated. Compared to proline, the CF3 group provides a decrease of the trans to cis amide bond isomerization energy and an increase of the cis conformer population.

A high-quality N - tert-butoxycarbonyl - L - pyroglutamic acid benzyl ester industrial production method

The invention relates to a bio-chemical technology field, in particular to a high-quality N - tert-butoxycarbonyl - L - pyroglutamic acid benzyl ester industrial production method, the raw material capture and L - pyroglutamic acid in the presence of a catalyst, with the chlorinated animal pen or bromination animal pen reaction to obtain the intermediate L - pyroglutamic acid benzyl ester; intermediate L - pyroglutamic acid benzyl ester organic phase under the catalyst condition, with the Boc anhydride reaction, to obtain the target crude N - tert-butoxycarbonyl - L - pyroglutamic acid benzyl ester; crude N - tert-butoxycarbonyl - L - pyroglutamic acid benzyl ester, in mixed crystals in the recrystallization solvent, for obtaining high-purity N - tert-butoxycarbonyl - L - pyroglutamic acid benzyl ester. Compared with the prior process, the present invention provides N - tert butoxycarbonyl - L - pyroglutamic acid benzyl ester industrial production method has the advantages of: can be efficient, stable production of the high-quality powder N - tert butoxycarbonyl - L - pyroglutamic acid benzyl ester, the purity is greater than 99.5%, a single impurities less than 0.1%.

Synthesis of the Siderophore Coelichelin and Its Utility as a Probe in the Study of Bacterial Metal Sensing and Response

A convergent total synthesis of the siderophore coelichelin is described. The synthetic route also provided access to acetyl coelichelin and other congeners of the parent siderophore. The synthetic products were evaluated for their ability to bind ferric iron and promote growth of a siderophore-deficient strain of the Gram-negative bacterium Pseudomonas aeruginosa under iron restriction conditions. The results of these studies indicate coelichelin and several derivatives serve as ferric iron delivery vehicles for P. aeruginosa.

Production technology of L-pyroglutamic acid benzyl ester

The invention belongs to the technical field of medicine chemical engineering, and particularly relates to a production technology of L-pyroglutamic acid benzyl ester. The technology comprises the following steps that an organic solvent, L-pyroglutamic acid and an acid binding agent are mixed and stirred to be uniform, the temperature of reaction liquid is controlled below 20 DEG C, benzyl chloride is dropwise added, after benzyl chloride is completely added, the temperature rises to 50-80 DEG C, a reaction is conducted for 6-20 h, raw materials are detected to react completely through TLC, aftertreatment is conducted after cooling is conducted, an organic layer is dried and filtered, concentration is conducted, and L-pyroglutamic acid benzyl ester is obtained. According to the production technology of L-pyroglutamic acid benzyl ester, 1,2-dichloroethane serves as a solvent for the reaction, after the reaction is conducted, water is added for liquid separation, the obtained organic solvent 1,2-dichloroethane solution is dried and can be distilled for recycling, environmental friendliness is achieved, and the production cost is greatly reduced. By means of the selected reaction condition, the reaction time is obviously shortened, and human and material resources are saved.

A new class of non-C2-symmetric ligands for oxidative and redox-neutral palladium-catalyzed asymmetric allylic alkylations of 1,3-diketones

We report the discovery, synthesis, and application of a new class of non-C2-symmetric phosphoramidite ligands derived from pyroglutamic acid for use in both oxidative and redox-neutral palladium-catalyzed asymmetric allylic alkylations of 1,3-diketones. The resulting chiral products are typically obtained in high yield with good to excellent levels of enantioselectivity.

THIOPHOSPHATE NUCLEOSIDES FOR THE TREATMENT OF HCV

Provided herein are compounds, compositions and methods for the treatment of Flaviviridae infections, including HCV infections. In certain embodiments, the compounds are according to Formula 2001: where PD, Base, RA and RB are as provided herein. In certain embodiments, compounds and compositions of nucleoside derivatives are disclosed, which can be administered either alone or in combination with other anti-viral agents.

Synthesis and evaluation of novel orally active p53-MDM2 interaction inhibitors

We have discovered and reported potent p53-MDM2 interaction inhibitors possessing dihydroimidazothiazole scaffold. Our lead showed strong activity in vitro, but did not exhibit antitumor efficacy in vivo for the low metabolic stability. In order to obtain orally active compounds, we executed further optimization of our lead by the improvement of physicochemical properties. Thus we furnished optimal compounds by introducing an alkyl group onto the pyrrolidine at the C-2 substituent to prevent the metabolism; and modifying the terminal substituent of the proline motif improved solubility. These optimal compounds exhibited good PK profiles and significant antitumor efficacy with oral administration on a xenograft model using MV4-11 cells having wild type p53.

Catalytic, enantioselective N-acylation of lactams and thiolactams using amidine-based catalysts

In contrast to alcohols and amines, racemic lactams and thiolactams cannot be resolved directly via enzymatic acylation or classical resolution. Asymmetric N-acylation promoted by amidine-based catalysts, particularly Cl-PIQ 2 and BTM 3, provides a convenient method for the kinetic resolution of these valuable compounds and often achieves excellent levels of enantioselectivity in this process. Density functional theory calculations indicate that the reaction occurs via N-acylation of the lactim tautomer and that cation-π interactions play a key role in the chiral recognition of lactam substrates.

Substituted 4-carboxymethylpyroglutamic acid diamides as potent and selective inhibitors of fibroblast activation protein

Fibroblast activation protein (FAP) belongs to the prolyl peptidase family. FAP inhibition is expected to become a new antitumor target. Most known FAP inhibitors often resemble the dipeptide cleavage products, with a boroproline at the P1 site; however, these inhibitors also inhibit DPP-IV, DPP-II, DPP8, and DPP9. Potent and selective FAP inhibitor is needed in evaluating that FAP as a therapeutic target. Therefore, it is important to develop selective FAP inhibitors for the use of target validation. To achieve this, optimization of the nonselective DPP-IV inhibitor 8 led to the discovery of a new class of substituted 4-carboxymethylpyroglutamic acid diamides as FAP inhibitors. SAR studies resulted in a number of FAP inhibitors having IC50 of 50 > 100 μM). Compounds 18a, 18b, and 19 are the only known potent and selective FAP inhibitors, which prompts us to further study the physiological role of FAP.

Synthetic approaches to peptides containing the l-Gln-l-Val-D(S)-Dmt motif

The pseudoprolines S-Dmo (5,5-dimethyl-4-oxaproline) and R-Dmt (5,5-dimethyl-4-thiaproline) have been used to study the effects of forcing a fully cis conformation in peptides. Synthesis of peptides containing these (which have the same configuration as l-Pro) is straightforward. However, synthesis of peptides containing S-Dmt is difficult, owing to the rapid cyclisation of l-Aaa-S-Dmt amides and esters to form the corresponding diketopiperazines (DKP); thus the intermediacy of l-Aaa-S-Dmt amides and esters must be avoided in the synthetic sequence. Peptides containing the l-Gln-l-Val-D(S)-Dmt motif are particularly difficult, owing to the insolubility of coupling partners containing Gln. Introduction of Gln as N-Boc-pyroglutamate overcame the latter difficulty and the dipeptide active ester BocPygValOC6F5 coupled in good yield with S-DmtOH. BocPygVal-S- DmtNH(CH2)2C6H4NO2 was converted quantitatively to BocGlnVal-S-DmtNH(CH2)2C6H4NO2 with ammonia, demonstrating the utility of this approach. Two peptide derivatives (CbzSerLysLeuGlnVal-S-DmtNH(CH2)2C6H4NO2 and CbzSerSerLysLeuGlnVal-S- DmtNH(CH2)2C6H4NO2) were assembled, using these new methods of coupling a dipeptide acid active ester with S-DmtOH and introduction of Gln as Pyg, followed by conventional peptide couplings. The presence of the Val caused these peptides to be cleaved very slowly by prostate-specific antigen (PSA) at Leu ↓ Gln, rather than the expected Gln ↓ Val.