40290-65-1Relevant academic research and scientific papers
Dynamic Kinetic Cross-Electrophile Arylation of Benzyl Alcohols by Nickel Catalysis
Guo, Peng,Wang, Ke,Jin, Wen-Jie,Xie, Hao,Qi, Liangliang,Liu, Xue-Yuan,Shu, Xing-Zhong
, p. 513 - 523 (2021/01/12)
Catalytic transformation of alcohols via metal-catalyzed cross-coupling reactions is very important, but it typically relies on a multistep procedure. We here report a dynamic kinetic cross-coupling approach for the direct functionalization of alcohols. The feasibility of this strategy is demonstrated by a nickel-catalyzed cross-electrophile arylation reaction of benzyl alcohols with (hetero)aryl electrophiles. The reaction proceeds with a broad substrate scope of both coupling partners. The electron-rich, electron-poor, and ortho-/meta-/para-substituted (hetero)aryl electrophiles (e.g., Ar-OTf, Ar-I, Ar-Br, and inert Ar-Cl) all coupled well. Most of the functionalities, including aldehyde, ketone, amide, ester, nitrile, sulfone, furan, thiophene, benzothiophene, pyridine, quinolone, Ar-SiMe3, Ar-Bpin, and Ar-SnBu3, were tolerated. The dynamic nature of this method enables the direct arylation of benzylic alcohol in the presence of various nucleophilic groups, including nonactivated primary/secondary/tertiary alcohols, phenols, and free indoles. It thus offers a robust alternative to existing methods for the precise construction of diarylmethanes. The synthetic utility of the method was demonstrated by a concise synthesis of biologically active molecules and by its application to peptide modification and conjugation. Preliminary mechanistic studies revealed that the reaction of in situ formed benzyl oxalates with nickel, possibly via a radical process, is an initial step in the reaction with aryl electrophiles.
Cyclopropane-derived peptidomimetics, design, synthesis, and evaluation of novel Ras farnesyltransferase inhibitors
Hillier,Davidson,Martin
, p. 1657 - 1671 (2007/10/03)
Trisubstituted cyclopropanes have previously been established as rigid replacements of dipeptide arrays in several biological systems. Toward further evaluating the utility of these dipeptide mimics in the design of novel CA1A2X-based inhibitors of Ras farnesyltransferase (FTase), the conformationally constrained, diastereomeric pseudopeptides CAbuψ[COcpCO]FM 7-9, the flexible analogue CAbuψ[CHOHCH2]FM (10), and the tetrapeptide CAbuFM (6) were prepared. The orientations of the two peptide backbone substituents and the phenyl group on the cyclopropane rings in 7-9 were specifically designed to probe selected topological features of the hydrophobic binding pocket of the A2 subsite of FTase. The syntheses of the requisite trisubstituted cyclopropane carboxylic acid 22 and the diastereomeric cyclopropyl lactones 32a,b featured diastereoselective intramolecular cyclopropanations of chiral allylic diazoacetates and a new method for introducing side chains onto the C-terminal amino acid of cyclopropane-derived dipeptide replacements via the opening of an N-Boc-aziridine with an organocuprate. These cyclopropane intermediates were then converted into the targeted FTase inhibitors 7-9 by standard peptide coupling techniques. The pseudopeptides 7-9 were found to be competitive inhibitors of Ras FTase with IC50s of 1055 nM for 7, 760 nM for 8, and 7200 nM for 9. The flexible analogue 10 of these constrained inhibitors exhibited a IC50 of 320 nM and hence was slightly more potent than 7 and 8. All of these pseudopeptides were less potent than the tetrapeptide parent CAbuFM (6), which had an IC50 of 38 nM. Because 7 and 8 are approximately equipotent, it appears that the orientation of the peptide backbone substituents on the cyclopropane rings in 7 and 8 do not have any significant effect on binding affinity and that multiple binding modes are possible without significant changes in affinity. On the other hand, this flexibility does not extend to the orientation of the side chain of the A2 residue as 7 and 8 were both nearly i order of magnitude more potent than 9. Comparison of the relative potencies of 6 and 10 suggests that the amide linkage between the A1 and the A2 residues of CA1A2X-derived FTase inhibitors is important.
Synthesis and biological evaluation of phosphonamidate peptide inhibitors of enkephalinase and angiotensin-converting enzyme
Elliott,Marks,Berg,Portoghese
, p. 1208 - 1216 (2007/10/02)
The effectiveness of phosphonamidate peptide analogues as inhibitors of rat kidney or human brain metallo-endopeptidase (enkephalinase, E.C. 3.4.24.11) and angiotensin-converting enzyme (ACE, 3.4.15.1) has been explored with a series of enkephalin analogu
A Convenient Synthesis of Met-enkephalin Using 1-β-Naphthalenesulphonyloxybenzotriazole for Peptide Bond Formation
Sharma, S. D.,Mathur, K. B.
, p. 227 - 229 (2007/10/02)
A convenient procedure for the synthesis of Met-enkephalin involving the use of 1-β-naphthalenesulphonyloxybenzotriazole as the peptide coupling reagent is described.Boc group is employed for the protection of α-NH2 functions of amino acids and its cleavage from the intermediate peptides is brought about by HCOOH in the presence of C6H5-OCH3 and SH-(CH2)2-SH without the formation of side products.The resulting formates are converted to the corresponding hydrochlorides prior to their coupling with the carboxy component.All the intermediate peptides have been obtained in high yields.
O-(N-ACYLAMINOACYL)-2-PYRIDYLMETHYLKETOXIMES AND THEIR USE IN PEPTIDE SYNTHESIS
Plucinski, Tomasz,Kupryszewski, Gotfryd
, p. 573 - 582 (2007/10/02)
Preparation of Leu-enkephalin, Met-enkephalin and one analog of Leu-enkephalin by using O-(N-acylaminoacyl)-2-pyridylketoximes is described.Both the side products and the unreacted active amino acid derivatives were removed by utilizing the formation of a copper complex with 2-pyridylmethylketoxime.
