β-Silyl Alkynoates: Versatile Reagents for Biocompatible and Selective Amide Bond Formation

Overview

Journal Sci Adv

Specialties Biology
Science

Date 2024 Sep 18

PMID 39292777

Authors

Khokan Choudhuri

Zhenguo Zhang

Teck-Peng Loh

Affiliations

Soon will be listed here.

Abstract

The study introduces a previously unidentified method for amide bond formation that addresses several limitations of conventional approaches. It uses the β-silyl alkynoate molecule, where the alkynyl group activates the ester for efficient amide formation, while the bulky TIPS (triisopropylsilane) group prevents unwanted 1,4-addition reactions. This approach exhibits high chemoselectivity for amines, making the method compatible with a wide range of substrates, including secondary amines, and targets the specific ε-amino group of lysine among the native amino ester's derivatives. It maintains stereochemistry during amide bond formation and TIPS group removal, allowing a versatile platform for postsynthesis modifications such as click reactions and peptide-drug conjugations. These advancements hold substantial promise for pharmaceutical development and peptide engineering, opening avenues for research applications.

References

Sharma S, Buchbinder N, Braje W, Handa S . Fast Amide Couplings in Water: Extraction, Column Chromatography, and Crystallization Not Required. Org Lett. 2020; 22(15):5737-5740. DOI: 10.1021/acs.orglett.0c01676. View

Nordstrom L, Vogt H, Madsen R . Amide synthesis from alcohols and amines by the extrusion of dihydrogen. J Am Chem Soc. 2008; 130(52):17672-3. DOI: 10.1021/ja808129p. View

Keller M, Blochl E, Wachtershauser G, Stetter K . Formation of amide bonds without a condensation agent and implications for origin of life. Nature. 1994; 368(6474):836-8. DOI: 10.1038/368836a0. View

Zeng H, Little H, Tiambeng T, Williams G, Guan Z . Multifunctional dendronized peptide polymer platform for safe and effective siRNA delivery. J Am Chem Soc. 2013; 135(13):4962-5. DOI: 10.1021/ja400986u. View

Krause T, Baader S, Erb B, Goossen L . Atom-economic catalytic amide synthesis from amines and carboxylic acids activated in situ with acetylenes. Nat Commun. 2016; 7:11732. PMC: 4906407. DOI: 10.1038/ncomms11732. View

Shen B, Makley D, Johnston J . Umpolung reactivity in amide and peptide synthesis. Nature. 2010; 465(7301):1027-32. PMC: 2945247. DOI: 10.1038/nature09125. View

Pramanik M, Mathuri A, Mal P . BuOLi-promoted terminal alkyne functionalizations by aliphatic thiols and alcohols. Org Biomol Chem. 2022; 20(13):2671-2680. DOI: 10.1039/d2ob00079b. View

Muramatsu W, Yamamoto H . Peptide Bond Formation of Amino Acids by Transient Masking with Silylating Reagents. J Am Chem Soc. 2021; 143(18):6792-6797. DOI: 10.1021/jacs.1c02600. View

Linstadt R, Peterson C, Lippincott D, Jette C, Lipshutz B . Stereoselective silylcupration of conjugated alkynes in water at room temperature. Angew Chem Int Ed Engl. 2014; 53(16):4159-63. DOI: 10.1002/anie.201311035. View

10.

Halima T, Masson-Makdissi J, Newman S . Nickel-Catalyzed Amide Bond Formation from Methyl Esters. Angew Chem Int Ed Engl. 2018; 57(39):12925-12929. DOI: 10.1002/anie.201808560. View

11.

Fritzemeier R, Gates A, Guo X, Lin Z, Santos W . Transition Metal-Free Trans Hydroboration of Alkynoic Acid Derivatives: Experimental and Theoretical Studies. J Org Chem. 2018; 83(17):10436-10444. DOI: 10.1021/acs.joc.8b01493. View

12.

Zhang Z, Li L, Xu H, Lee C, Jia Z, Loh T . Silicon-Containing Thiol-Specific Bioconjugating Reagent. J Am Chem Soc. 2024; 146(3):1776-1782. DOI: 10.1021/jacs.3c12050. View

13.

Bragg P, Hou C . Subunit composition, function, and spatial arrangement in the Ca2+-and Mg2+-activated adenosine triphosphatases of Escherichia coli and Salmonella typhimurium. Arch Biochem Biophys. 1975; 167(1):311-21. DOI: 10.1016/0003-9861(75)90467-1. View

14.

Ma L, Wang C, He Z, Cheng B, Zheng L, Huang K . Peptide-Drug Conjugate: A Novel Drug Design Approach. Curr Med Chem. 2017; 24(31):3373-3396. DOI: 10.2174/0929867324666170404142840. View

15.

Nogami M, Hirano K, Morimoto K, Tanioka M, Miyamoto K, Muranaka A . Alkynylboration Reaction Leading to Boron-Containing π-Extended cis-Stilbenes as a Highly Tunable Fluorophore. Org Lett. 2019; 21(9):3392-3395. DOI: 10.1021/acs.orglett.9b01132. View

16.

Gunanathan C, Ben-David Y, Milstein D . Direct synthesis of amides from alcohols and amines with liberation of H2. Science. 2007; 317(5839):790-2. DOI: 10.1126/science.1145295. View

17.

Wipf P, Graham T . Synthesis and hetero-Michael addition reactions of 2-alkynyl oxazoles and oxazolines. Org Biomol Chem. 2004; 3(1):31-5. DOI: 10.1039/b413604g. View

18.

Teng S, Ng E, Zhang Z, Soon C, Xu H, Li R . Alkynone β-trifluoroborates: A new class of amine-specific biocompatible click reagents. Sci Adv. 2023; 9(17):eadg4924. PMC: 10132755. DOI: 10.1126/sciadv.adg4924. View

19.

Wang Y, Zhu D, Tang L, Wang S, Wang Z . Highly efficient amide synthesis from alcohols and amines by virtue of a water-soluble gold/DNA catalyst. Angew Chem Int Ed Engl. 2011; 50(38):8917-21. DOI: 10.1002/anie.201102374. View

20.

Go S, Lee G, Hong S . Highly Regioselective and E/ Z-Selective Hydroalkylation of Ynone, Ynoate, and Ynamide via Photoredox Mediated Ni/Ir Dual Catalysis. Org Lett. 2018; 20(15):4691-4694. DOI: 10.1021/acs.orglett.8b02017. View