Tantalum-Catalyzed Amidation of Amino Acid Homologues

Eight dipeptides containing antifibrinolytic agents (tranexamic acid, aminocaproic acid, 4-(aminomethyl)benzoic acid, and glycine—natural amino acids) were synthesized in a three-step process with good or very good yields. DMT/NMM/TsO− (4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium toluene-4-sulfonate) was used as a coupling reagent. Hemolysis tests were used to study the effects of the dipeptides on blood components. Blood plasma clotting tests were used to examine their effects on thrombin time (TT), prothrombin time (PT), and the activated partial thromboplastin time (aPTT). The level of hemolysis did not exceed 1%. In clotting tests, TT, PT, and aPTT did not differentiate any of the compounds. The prothrombin times for all amides 1–8 were similar. The obtained results in the presence of amides 1–4 and 8 were slightly lower than for the other compounds and the positive control, and they were similar to the results obtained for TA. In the case of amide 3, a significantly decreased aPTT was observed. The aPTTs observed for plasma treated with amide 3 and TA were comparable. In the case of amide 6 and 8, TT values significantly lower than for the other compounds were found. The clot formation and fibrinolysis (CFF) assay was used to assess the influence of the dipeptides on the blood plasma coagulation cascade and the fibrinolytic efficiency of the blood plasma. In the clot formation and fibrinolysis assay, amides 5 and 7 were among the most active compounds. The cytotoxicity and genotoxicity of the synthesized dipeptides were evaluated on the monocyte/macrophage peripheral blood cell line. The dipeptides did not cause hemolysis at any concentrations. They exhibited no significant cytotoxic effect on SC cells and did not induce significant DNA damage.

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“…344.2311). The analytical data are in agreement with those reported previously in the literature [ 49 ].…”

Section: Methodssupporting

confidence: 91%

Synthesis and Hemostatic Activity of New Amide Derivatives

et al. 2022

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“…In 2021, Muramatsu and Yamamoto reported the direct peptide-bond formation starting from unprotected amino acids achieved by combining HSi[OCH(CF 3 ) 2 ] 3 , acting as a condensation reagent, with N -( tert -butyldimethylsilyl)- N -methyltrifluoroacetamide, acting as a transient masking group. 12 This method provided the corresponding not epimerized dipeptides in high yield, without the implementation of a conventional deprotection process after the condensation step.…”

Section: Table 1 Results Of Experiments Conducted Using...mentioning

confidence: 99%

Amidation of α-Amino Acids Using Dichloro(methyl)(3,3,3-trifluoropropyl)silane and Imidazole without Conventional Protection and Deprotection of α-Amino Group

Nobuta¹,

Morishita²,

Suto³

et al. 2022

Synlett

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Amidation of amino acids using dichloro(methyl)(3,3,3-trifluoropropyl)silane (MTFPSCl2) and imidazole is described. MTFPSCl2 activates the carboxy group and protects the α-amino group of amino acids. The amidation proceeded with 19 amino acids and 19 amines, including α-branched amines and anilines; the corresponding amino acid amides were synthesized in good-to-high yields (up to 96%) with low-to-no racemization.

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“…[87] The authors suggest an interesting mechanism involving co-catalysis with isothiazolones coating the surface of the nanoparticles. Group V metals catalysts, such as Nb 2 O 5 [91,99,100] and Ta(OMe) 5 [94] have also been applied to direct amidation of carboxylic acids and have desirable features, such as high yields with a wide substrate scope, water tolerance and ability to couple β-amino acids through bidentate substrate chelation after initial in-situ generation of a silyl ester from the corresponding carboxylic acid and TMS-Imidazole ( Figure 10). [94] While the niobium catalysts required highly elevated temperatures (refluxing toluene) the tantalum catalyst could operate near room temperature although its use is complicated by significantly higher cost and scarcity.…”

Section: Other Metalsmentioning

confidence: 99%

“…[101] The [87] Al/Zr/Ti-SBA-15 Toluene 110 50* None Fontaine [88] CuI DMF 60 5 None Yin [89] FeCl 3 Toluene 75 20 None Sureshbabu [90] HfCp 2 Cl 2 Et 2 O r.t. 10 4 Å M.S. Adolfsson [80] N 2 O 5 Toluene 40 50* None Shimizu [91] (NH 4 ) 2 Ce(NO 3 ) 6 Neat Microwave 2 None Markiewicz [92] NiCl 2 Toluene 110 10 None Huang [93] Ta(OMe) 5 Neat 40 10 None Yamamoto [94] TiCp 2 Cl 2 THF 70-80 10 4 Å M.S. Huang [85] TiO 2 Neat 100 36* None Cravotto [95] Zr [86] Zr-AzoBDC THF 70 2-10 4 Å M.S.…”

Section: Other Metalsmentioning

confidence: 99%

Recent developments in catalytic amide bond formation

Todorovic

Perrin

2020

Peptide Science

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Amide bond forming reactions are critical for both polypeptide synthesis and medicinal chemistry. Most current approaches for amidation employ stoichiometric activating agents, but such methods are neither atom economical nor synthetically elegant. Catalytic approaches for amidation are potentially green and more ideal substitutes for current standard methods and thus are the subject of this review. Such methods face significant thermodynamic and kinetic barriers and have, as a result, historically

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Tantalum-Catalyzed Amidation of Amino Acid Homologues

Cited by 35 publications

References 41 publications

Synthesis and Hemostatic Activity of New Amide Derivatives

Synthesis and Hemostatic Activity of New Amide Derivatives

Amidation of α-Amino Acids Using Dichloro(methyl)(3,3,3-trifluoropropyl)silane and Imidazole without Conventional Protection and Deprotection of α-Amino Group

Recent developments in catalytic amide bond formation

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