- Dynamic Kinetic Cross-Electrophile Arylation of Benzyl Alcohols by Nickel Catalysis
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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.
- Guo, Peng,Wang, Ke,Jin, Wen-Jie,Xie, Hao,Qi, Liangliang,Liu, Xue-Yuan,Shu, Xing-Zhong
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supporting information
p. 513 - 523
(2021/01/12)
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- Visible-Light-Driven, Copper-Catalyzed Decarboxylative C(sp3)?H Alkylation of Glycine and Peptides
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Despite a well-developed and growing body of work in Cu catalysis, the potential of Cu to serve as a photocatalyst remains underexplored. Reported herein is the first example of visible-light-induced Cu-catalyzed decarboxylative C(sp3)?H alkylation of glycine for preparing α-alkylated unnatural α-amino acids. It merits mentioning that the mild conditions and the good functional-group tolerance allow the modification of peptides using this method. The mechanistic studies revealed that a radical–radical coupling pathway is involved in the reaction.
- Wang, Chao,Guo, Mengzhun,Qi, Rupeng,Shang, Qinyu,Liu, Qiang,Wang, Shan,Zhao, Long,Wang, Rui,Xu, Zhaoqing
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supporting information
p. 15841 - 15846
(2018/11/23)
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- Amide and Peptide Bond Formation in Water at Room Temperature
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A general and environmentally responsible method for the formation of amide/peptide bonds in an aqueous micellar medium is described. Use of uronium salt (1-cyano-2-ethoxy-2-oxoethylidenaminooxy)dimethylaminomorpholinocarbenium hexafluorophosphate (COMU) as a coupling reagent, 2,6-lutidine, and TPGS-750-M represents mild conditions associated with these valuable types of couplings. The aqueous reaction medium is recyclable leading to low E Factors.
- Gabriel, Christopher M.,Keener, Megan,Gallou, Fabrice,Lipshutz, Bruce H.
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supporting information
p. 3968 - 3971
(2015/09/01)
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- A one-pot saponification-coupling sequence suitable for C-terminus peptide elongation using lithium carboxylates
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An efficient procedure has been developed for the saponification of common peptide esters, followed by straightforward coupling of the lithium carboxylate. Adding some water to the reaction medium gave faster saponification and did not interfere with the coupling reagent. As peptide chemistry constitutes a major application of the amidation reaction, amino acid substrates were chosen for this study, monitoring both yields and epimerization of the peptides obtained. Georg Thieme Verlag Stuttgart New York.
- Azzouz, Rabah,Petit, Sylvain,Rouchet, Jean-Baptiste,Bischoff, Laurent
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supporting information
p. 1843 - 1846
(2014/08/18)
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- Synthesis and electrochemical studies of disubstituted ferrocene/dipeptide conjugates with sulfur-containing side chains
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A series of 1 1'-disubstituted ferrocenoyl peptides incorporating dipeptide sidearms has been synthesized and studied electrochemically. The target peptides include ferrocene as an electrochemical reporter, sulfur-containing amino acids (L-methionine, S-methyl-L-cysteine, S-trityl-L-cysteine, S-benzhydryl-L- cysteine) as metal binding agents, and amino acids with non-polar side chains (L-alanine, L-valine, L-phenylalanine) as spacers between reporter and metal binding groups. Ferrocene/dipeptide conjugates were prepared using solution phase peptide synthesis methods employing a BOC-protecting group strategy and HBTU- (O-(benzotriazol-1-yl)-N, N, N', N'-tetramethyluronium hexafluorophosphate) mediated peptide coupling. The electrochemical properties of these 1, 1'-substituted ferrocenoyl peptides have been characterized using cyclic voltammetry. All exhibit fully reversible one electron oxidation steps; forward sweep half wave peaks (EF), reverse sweep half wave peaks (ER), peak separations (DEP) and half wave potentials (E1/2) are reported. Finally, towards the goal of utilizing ferrocenoyl peptides to detect heavy metals in solution, the response of these ferrocene/dipeptide conjugates to metal cations (zinc(II), mercury(II), cadmium(II), lead(II), silver(I)) has been examined. Monitoring changes in the potential of the Fe(II)/Fe(III) redox couple to follow peptide/metal interactions, we have probed the influence of the spacer unit between the redox reporter and the metal-binding amino acid, and shown that these systems respond to mercury(II) more strongly than to other heavy metal ions.
- Scully, Conor C.G.,Rutledge, Peter J.
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scheme or table
p. 5653 - 5659
(2010/10/02)
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- Synthesis and biological evaluation of potential bisubstrate inhibitors of protein farnesyltransferase. Design and synthesis of functionalized imidazoles
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A novel series of compounds, derived from 2,5-functionalized imidazoles, have been synthesized as potential bisubstrate inhibitors of protein farnesyltransferase (FTase) using structure-based design. These compounds have a 1,4-diacid chain and a tripeptid
- De Figueiredo, Renata Marcia,Coudray, Laetitia,Dubois, Joelle
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p. 3299 - 3309
(2008/09/20)
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- Convenient high yielding gram scale solution synthesis of methionine-enkephalin
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A simple, large-scale synthesis of a cytokine, methionine-enkephalin, Tyr-Gly-Gly-Phe-Met, has been elaborated. Classical solution peptide chemistry methods without protection of amino acid side-chain functions and l+(2+2) segment condensation were used. A nine-step synthesis from commercial amino acid derivatives was developed with yields ranging from 86% to 99%, averaging 92%. The purity of all intermediates was found to be 99.0-100% by HPLC. The process has been used to prepare greater than 150 g quantities of the pentapeptide as a monohydrate of 100% purity. Hydantoin formation was observed during saponification of Boc-TyrGly-Gly-Phe-Met-OMe and minimised.
- Masiukif.wicx, Elzbieta,Rzeszotarska, Barbara
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p. 1672 - 1675
(2007/10/03)
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- A new coupling reagent for peptide synthesis. Benzotriazolvyloxy-bis (pyrroltdino) -carbonium hexaflouorophosphate (BBC)
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Benzotriazolyloxy-bis(pyrrolidino)-carbonium hexa- fluorophosphate (BBC) is found to be a new excellent coupling reagent devoid of cytotoxic by-product instead of HBTU and BOP. It has been applied in the solution and solid phase peptide synthesis.
- Chen, Shaoqing,Xu, Jiecheng
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p. 647 - 650
(2007/10/02)
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- PENTAFLUOROPHENYL DIPHENYLPHOSPHINATE A NEW EFFICIENT COUPLING REAGENT IN PEPTIDE CHEMISTRY
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Pentafluorophenyl diphenylphosphinate was found to be a new efficient coupling reagent for the racemization-free synthesis of peptides.It has been applied in both the solution and the solid phase peptide synthesis.
- Chen, Shaoqing,Xu, Jiecheng
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p. 6711 - 6714
(2007/10/02)
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- THE CINNAMYLOXYCARBONYL GROUP AS A NEW AMINO-PROTECTING GROUP
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A new urethane-type protecting group for amines, cinnamyloxycarbonyl (Coc) group, is described.The cleavage of the Coc group is effectively catalyzed by 5 molpercent of in the presence of formic acid, pyridine, and N-hydroxysuccinimide in ref
- Kinoshita, Hideki,Inomata, Katsuhiko,Kameda, Takuo,Kotake, Hiroshi
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p. 515 - 518
(2007/10/02)
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- O-(N-ACYLAMINOACYL)-2-PYRIDYLMETHYLKETOXIMES AND THEIR USE IN PEPTIDE SYNTHESIS
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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.
- Plucinski, Tomasz,Kupryszewski, Gotfryd
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p. 573 - 582
(2007/10/02)
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- SYNTHESIS OF PENTAPEPTIDES RELATED BOTH TO SUBSTANCE P C-TERMINAL FRAGMENT AND MET-ENKEPHALIN
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Six pentapeptide amides related both to Substance P C-terminal fragment and to Met-enkephalin have been synthesized.Syntheses were effected by coupling fragments 3 + 2 in solution.The DCC + HOBt method was used for synthesis of peptide fragments and final
- Lipkowski, Andrzej W.,Misicka, Aleksandra,Drabarek, Stefania
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p. 813 - 818
(2007/10/02)
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- A Convenient Synthesis of Met-enkephalin Using 1-β-Naphthalenesulphonyloxybenzotriazole for Peptide Bond Formation
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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.
- Sharma, S. D.,Mathur, K. B.
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p. 227 - 229
(2007/10/02)
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- Analgesic compounds
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Compounds of the formula STR1 and pharmaceutically acceptable non-toxic acid addition salts thereof, in which L and D, when applicable, define the chirality; R1 is hydrogen, C1 -C3 primary alkyl, or allyl; R2 is hydrogen or C1 -C3 primary alkyl, subject to the limitation that when R1 is allyl, R2 is hydrogen; R3 is hydrogen or C1 -C3 primary alkyl; R4 is C1 -C4 primary or secondary alkyl; R5 is hydrogen or C1 -C4 primary or secondary alkyl; R6 is hydrogen or C1 -C3 primary alkyl; R7 is hydrogen or C1 -C3 primary alkyl; Y is hydrogen or acetyl; Z is hydrogen of STR2 in which R8 is C1 -C3 alkyl or hydrogen; and W is isopropyl, --VR9, or --CH2 --X--CH3, in which V is O or S, R9 is C1 -C4 alkyl or aralkyl, and X is O, S, or --CH2 --, subject to the limitation that, when W is isopropyl, R7 is C1 -C3 primary alkyl; are useful analgesic agents.
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- The Synthesis of Cystine Peptides by Iodine Oxidation of S-Trityl-cysteine and S-Acetamidomethyl-cysteine Peptides
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Previously repoted studies of the iodine oxidation of S-trityl-cysteine peptides and S-acetamidomethyl-cysteine peptides, leading directly to cystine peptides, have been extended.Detailed investigations have been made of the reactivities of the S-trityl a
- Kamber, Bruno,Hartmann, Albert,Eisler, Karel,Riniker, Bernhard,Rink, Hans,et al.
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p. 899 - 915
(2007/10/02)
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- Synthesis and pharmacological study of some enkephalin analogs in relation to the plurality of opiate receptors
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We have synthesized a series of enkephalin analogs and measured their affinity for each type of 'opiate' receptor, the μ receptor and the δ receptor. Furthermore, we have determined their respective antinociceptive activity after intracerebroventricular i
- Audigier,Mazarguil,Gout,Cros
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p. 173 - 177
(2007/10/02)
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