69209-72-9Relevant academic research and scientific papers
A mild Boc deprotection and the importance of a free carboxylate
Thaqi, Ali,McCluskey, Adam,Scott, Janet L.
, p. 6962 - 6964 (2008)
We report a facile and rapid removal of Boc protecting groups using microwave heating in H2O, with deprotection only requiring a free carboxylic acid group in the starting material. Unlike previous approaches, no additional reagents are required.
Design, synthesis and biological evaluation of dipeptides as novel non-covalent 20S proteasome inhibitors
Yang, Ya-Jun,Wang, Ke,Yang, Ying,Lai, Fang-Fang,Chen, Xiao-Guang,Xiao, Zhi-Yan
, p. 436 - 451 (2021/04/22)
Based on the interaction modes of the natural 20S proteasome inhibitors TMC-95A, we have previously discovered a dipeptide 1. To explore the SAR around compound 1, we designed and synthesized a series of dipeptides (8–38) with a fragment-based strategy. Among them, nine compounds showed significant inhibitory activities against the chymotrypsin-like activity of human 20S proteasome with IC50 values at the submicromolar level, which were comparable or even superior to the parent compound 1. Meanwhile, they displayed no significant inhibition against trypsin-like and caspase-like activities of 20S proteasome. The results suggested the feasibility to design dipeptides as novel and potent 20S proteasome inhibitors. (Figure presented.).
TRANSGLUTAMINASE 2 (TG2) INHIBITORS
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, (2020/03/02)
Described herein are compounds and pharmaceutical compositions containing such compounds which inhibit transglutaminase 2 (TG2). Also described herein are methods for using such TG2 inhibitors, alone or in combination with other compounds, for treating diseases or conditions that would benefit from TG2 inhibition.
Synthesis, SAR and biological studies of sugar amino acid-based almiramide analogues: N-methylation leads the way
Das, Dipendu,Khan, Hina P. A.,Shivahare, Rahul,Gupta, Suman,Sarkar, Jayanta,Siddiqui, Mohd. Imran,Ampapathi, Ravi Sankar,Chakraborty, Tushar Kanti
, p. 3337 - 3352 (2017/04/21)
Leishmaniasis, caused by the protozoan parasites of the genus Leishmania, is one of the most neglected diseases endemic in many continents posing enormous global health threats and therefore the discovery of new antileishmanial compounds is of utmost urgency. The antileishmanial activities of a library of sugar amino acid-based linear lipopeptide analogues were examined with the aim to identify potential drug candidates to treat visceral leishmaniasis. It was found that among the synthesized analogues, most of the permethylated compounds exhibited more activity in in vitro studies against intra-macrophagic amastigotes than the non-methylated analogues. SAR and NMR studies revealed that introduction of the N-methyl groups inhibited the formation of any turn structure in these molecules, which led to their improved activities.
N-Acryloyl amino acid esters and peptides as radical acceptors in photoinduced decarboxylative radical reaction
Osaka, Kazuyuki,Sugie, Mai,Yamawaki, Mugen,Morita, Toshio,Yoshimi, Yasuharu
, p. 50 - 55 (2015/12/04)
The photoinduced electron transfer (PET) promoted decarboxylative radical additions of carboxylic acids using N-acryloyl amino acid esters and peptides as radical acceptors smoothly afforded the corresponding modified amino acids and peptides under mild reaction conditions. The radical additions of α-amino acids led to the formation of γ- and α-dipeptide, and peptides underwent peptide coupling via decarboxylation.
Direct modification of tripeptides using photoinduced decarboxylative radical reactions
Maeda, Kousuke,Saito, Hikaru,Osaka, Kazuyuki,Nishikawa, Keisuke,Sugie, Mai,Morita, Toshio,Takahashi, Ichiro,Yoshimi, Yasuharu
, p. 1117 - 1123 (2015/01/30)
In order to explore the applicability of photoinduced electron transfer (PET) promoted decarboxylative reactions to the direct modification of peptides, a study was performed to assess the influence of amino acid side chains on photoreactions of N-terminal protected tripeptides. Photoinduced decarboxylation reactions of tripeptides, which are composed of central amino acids that possess alkyl, phenyl, thioether, hydroxy, and amide containing side chains, in the presence or absence of acrylonitrile and a thiol were found to proceed smoothly to give the corresponding radical addition, H-abstraction, and substitution products. Although photoreactions of tripeptides containing central amino acids with phenol and indole (Tyr and Trp) moieties do not take place efficiently, appropriate protection of these groups enables the substrates to undergo smooth photoinduced decarboxylative reactions.
An efficient and cost-effective approach to kahalalide F N-terminal modifications using a nuisance algal bloom of Bryopsis pennata
Wang, Bin,Waters, Amanda L.,Valeriote, Frederick A.,Hamann, Mark T.
, p. 1849 - 1854 (2015/06/08)
Background: Kahalalide F (KF) and its isomer iso-kahalalide F (isoKF), both of which can be isolated from the mollusk Elysia rufescens and its diet alga Bryopsis pennata, are potent cytotoxic agents that have advanced through five clinical trials. Due to a short half-life, narrow spectrum of activity, and a modest response in patients, further efforts to modify the molecule are required to address its limitations. In addition, due to the high cost in producing KF analogues using solid phase peptide synthesis (SPPS), a degradation and reconstruction approach was employed using natural KF from a seasonal algal bloom to generate KF analogues. Methods: N-protected KF was carefully hydrolyzed at the amide linkage between L-Thr12 and D-Val13 using dilute HCl. The synthesis of the C-terminal fragment began with the formation of hexanoic succinimide ester, followed by a reaction with dipeptides. The final coupling reaction was performed between the semisynthesized Fmoc-KF hydrolysis product and the C-terminal fragment, followed by the deprotection of the Fmoc group. Results: Six KF analogues with an addition of an amino acid residue on the N-terminal chain, D-Val14-isoKF (2), Val13-Val14-isoKF (3), D-Leu14-isoKF (4), D-Pro14-isoKF (5), D-Phe14-isoKF (6), and 3,4-2F-D-Phe14-isoKF (7) were prepared using semisynthesis at the exposed N-terminal chain. Conclusions: The overall yield of the medication was 45%. This approach is economical, efficient and amendable to large-scale production while eliminated a nuisance algal bloom. General significance: B. pennata blooms are capable of producing KF in good yields. The semisynthesis from the natural product produced N-terminal modifications for the construction of inexpensive semisynthetic KF libraries.
Synthesis of 2-amino-5-aryl-1,3,4-thiadiazolopeptides as potent antitubercular agents
Asif, Karigar,Himaja,Ramana,Sikarwar, Mukesh S.
, p. 2739 - 2743 (2012/09/22)
A novel series of 2-amino-5-aryl-thiadiazole analogs of amino acids and dipeptides were synthesized using 1-ethyl-3-(3- dimethylaminopropyl)carbodiimide as coupling agent and N-methyl morpholine (NMM) as base. Structure of all the newly synthesized compounds was confirmed by IR, 1H NMR, 13C NMR and mass spectral data. All the synthesized compounds were screened for their antitubercular, antibacterial and antifungal activity.
Synthesis and antimicrobial activity of 2-amino-5-aryl-5H-thiazolo [4,3-b]-1,3,4-thiadiazole derivatives of amino acids and peptides
Himaja,Karigar, Asif A.,Prathap, Jagadeesh K.,Ramana,Mali, Sunil V.
, p. 125 - 128 (2013/09/24)
A new series of 2-amino-5-aryl-5H-thiazolo [4,3-b]-1,3,4-thiadiazole derivatives of amino acids and peptides were synthesized by solution phase technique. The synthesized compounds were confirmed by FTIR, 1H NMR and mass spectral analysis and evaluated for antitubercular activity, fungicidal activity and bactericidal activity. All the synthesized compounds have shown potent antitubercular activity. Regarding antibacterial activity some of the compounds like 3f, 3i and 3j were found to have significant antibacterial activity against Gram-positive bacteria S. aureus, E. fecalis, however, they were found to have less activity against Gram-negative bacteria E. coli, K. pneumoniae. Antifungal results indicated that some of the derivatives like 3i and 3j possessed a broad spectrum of activity against tested fungi A. nigerand C. albicans.
A facile synthesis and crystallographic analysis of N-protected β-amino alcohols and short peptaibols
Jadhav, Sandip V.,Bandyopadhyay, Anupam,Benke, Sushil N.,Mali, Sachitanand M.,Gopi, Hosahudya N.
supporting information; body text, p. 4182 - 4187 (2011/06/28)
A facile, efficient and racemization-free method for the synthesis of N-protected β-amino alcohols and peptaibols using N-hydroxysuccinimide active esters is described. Using this method, dipeptide, tripeptide and pentapeptide alcohols were isolated in high yields. The conformations in crystals of β-amino alcohol, dipeptide and tripeptide alcohols were analysed, with a well-defined type III β-turn being observed in the tripeptide alcohol crystals. This method is found to be compatible with Fmoc-, Boc- and other side-chain protecting groups.
