Application of AlMe3-mediated amidation reactions to solution phase peptide synthesis

Martin, Stephen F.; Dwyer, Michael P.; Lynch, Christopher L.

doi:10.1016/s0040-4039(98)00071-9

Cited by 27 publications

(49 citation statements)

References 10 publications

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“…[20] The Fmoc group of the resin-linked eight tridecapeptides 32 was exchanged with the NTAs tructure by treatment with piperidine and then with carboxylic acid 23,( 1-cyano-2-ethoxy-2-oxoethylidenaminooxy)dimethylamino-morpholino-carbenium hexafluorophosphate (COMU), [40] and 2,4,6-collidine. The dimethyl aluminuma mide species, generated by mixinga ne quimolar amount of amine 28 and AlMe 3 , [41,42] induced the ester-amide exchange to simultaneously cleave the Wang linker and introduce the CTA. [43,44] Consequently, 1 and its seven E/Z isomers 2-8 were released from the resin.…”

Section: Resultsmentioning

confidence: 99%

Divergent Solid‐Phase Synthesis and Biological Evaluation of Yaku'amide B and Its Seven E/Z Isomers

Kamiya

Miura

Itoh

et al. 2020

Chemistry A European J

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Yaku′amide B (1) inhibits cancer cell growth through a unique mechanism of action. Compound 1 binds to mitochondrial FoF1‐ATP synthase, inhibits ATP production, and enhances ATP hydrolysis. The presence of one (E)‐ and two (Z)‐α,β‐dehydroisoleucines (ΔIle) in the linear 13‐mer sequence is the most unusual structural feature of 1. To uncover the biological importance of these residues, we synthesized 1 and its seven E/Z isomers 2–8 by devising a new divergent solid‐phase strategy. Both the (E)‐ and (Z)‐ΔIle residues were stereoselectively constructed by traceless Staudinger ligation on resin to ultimately deliver 1–8. All isomers 2–8 displayed effects on the inhibition of cell growth and ATP production, and enhanced ATP hydrolysis, thus indicating that 2–8 share the same mode of action as 1. The least potent isomer, 8, was isomeric at three ΔIle residues of the most potent 1. These findings together indicate that the E/Z stereochemistry of the three ΔIle residues controls the magnitude of the biological functions of 1.

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Section: Resultsmentioning

confidence: 99%

Divergent Solid‐Phase Synthesis and Biological Evaluation of Yaku'amide B and Its Seven E/Z Isomers

Kamiya

Miura

Itoh

et al. 2020

Chemistry A European J

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“…A synthesis of oligopeptides in solution employing the modified Weinreb's method involved the treatment of N-protected amino acids with trimethylaluminum (44) followed by the addition of N-protected amino acid esters or peptide esters (Scheme 21). 96 The epimerization in the preparation of dipeptides by this method was observed to be less than 1% by reverse phase HPLC analysis, but in the preparation of tripeptides, 10-20% of epimerization was detected. …”

Section: Lewis Acid Mediated N-acylationmentioning

confidence: 79%

N-Acylation in combinatorial chemistry

Katritzky¹,

Suzuki²,

Singh³

2004

Arkivoc

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“…In our previous work, [7] we found that 4a nd 5-hydroxyacids could be activated for subsequent peptide coupling through intramolecular lactonization, followed by treatment with the appropriate amine nucleophile.Inthe same vein, the free 4-hydroxyacids from 10 were lactonized by treatment with EDC.Lactone opening of 12 with H-Ala-OtBu (15)was carried out in the presence of AlMe 3 to afford alcohol 16 in 63 %y ield (Scheme 1B). [22] Finally,u se of Mitsunobu conditions [23] (DIAD,P Ph 3 )o n16 effected an intramolecular displacement of the secondary alcohol by the pendant guanidine to complete the synthesis of the l-enduracididine [15] -d-alanine [16] dipeptide fragment of enduracidin (17). Our chemoenzymatic route compares favorably to previous synthetic approaches [14] to l-enduracididine (see Table S2 for comparison), which typically result in poor stereocontrol at C4.…”

Section: Methodsmentioning

confidence: 87%

Characterization of a Citrulline 4‐Hydroxylase from Nonribosomal Peptide GE81112 Biosynthesis and Engineering of Its Substrate Specificity for the Chemoenzymatic Synthesis of Enduracididine

2019

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The GE81112 tetrapeptides are a small family of unusual nonribosomal peptide congeners with potent inhibitory activity against prokaryotic translation initiation. With the exception of the 3‐hydroxy‐l‐pipecolic acid unit, little is known about the biosynthetic origins of the non‐proteinogenic amino acid monomers of the natural product family. Here, we elucidate the biogenesis of the 4‐hydroxy‐l‐citrulline unit and establish the role of an iron‐ and α‐ketoglutarate‐dependent enzyme (Fe/αKG) in the pathway. Homology modelling and sequence alignment analysis further facilitate the rational engineering of this enzyme to become a specific 4‐arginine hydroxylase. We subsequently demonstrate the utility of this engineered enzyme in the synthesis of a dipeptide fragment of the antibiotic enduracidin. This work highlights the value of applying a bioinformatics‐guided approach in the discovery of novel enzymes and engineering of new catalytic activity into existing ones.

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Application of AlMe3-mediated amidation reactions to solution phase peptide synthesis

Cited by 27 publications

References 10 publications

Divergent Solid‐Phase Synthesis and Biological Evaluation of Yaku'amide B and Its Seven E/Z Isomers

Divergent Solid‐Phase Synthesis and Biological Evaluation of Yaku'amide B and Its Seven E/Z Isomers

N-Acylation in combinatorial chemistry

Characterization of a Citrulline 4‐Hydroxylase from Nonribosomal Peptide GE81112 Biosynthesis and Engineering of Its Substrate Specificity for the Chemoenzymatic Synthesis of Enduracididine

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