Optimized Synthesis of Hydrogen-bond Surrogate Helices: Surprising Effects of Microwave Heating on the Activity of Grubbs Catalysts

Overview

Journal Org Lett

Publisher American Chemical Society

Specialties Biochemistry
Chemistry

Date 2006 Dec 1

PMID 17134282

Citations 25

Authors

Ross N Chapman

Paramjit S Arora

Affiliations

Soon will be listed here.

Abstract

This manuscript discusses microwave-assisted solid-phase synthesis of hydrogen-bond surrogate based alpha-helices and analogues by ring-closing metathesis (RCM). Microwave-mediated RCM allows access to a greater variety of amino acid residues in the macrocycles in shorter reaction times and higher yields compared to conventional heating. Surprisingly, we discovered that the Grubbs II catalyst is highly active under the influence of microwaves but catalytically dead under oil-bath conditions for the metathesis of these peptide bisolefins. [reaction: see text]

Citing Articles

A Bicyclic Analog of the Linear Peptide Arodyn Is a Potent and Selective Kappa Opioid Receptor Antagonist.

Gisemba S, Ferracane M, Murray T, Aldrich J Molecules. 2024; 29(13).

PMID: 38999061 PMC: 11243530. DOI: 10.3390/molecules29133109.

Therapeutic peptides: current applications and future directions.

Wang L, Wang N, Zhang W, Cheng X, Yan Z, Shao G Signal Transduct Target Ther. 2022; 7(1):48.

PMID: 35165272 PMC: 8844085. DOI: 10.1038/s41392-022-00904-4.

Bent Into Shape: Folded Peptides to Mimic Protein Structure and Modulate Protein Function.

Merritt H, Sawyer N, Arora P Pept Sci (Hoboken). 2021; 112(1).

PMID: 33575525 PMC: 7875438. DOI: 10.1002/pep2.24145.

H-Bond Surrogate-Stabilized Shortest Single-Turn α-Helices: sp Constraints and Residue Preferences for the Highest α-Helicities.

Pal S, Banerjee S, Kumar A, Prabhakaran E ACS Omega. 2020; 5(23):13902-13912.

PMID: 32566857 PMC: 7301546. DOI: 10.1021/acsomega.0c01277.

Macrocyclic Peptides Uncover a Novel Binding Mode for Reversible Inhibitors of LSD1.

Yang J, Talibov V, Peintner S, Rhee C, Poongavanam V, Geitmann M ACS Omega. 2020; 5(8):3979-3995.

PMID: 32149225 PMC: 7057333. DOI: 10.1021/acsomega.9b03493.

References

Scholl M, Ding S, Lee C, Grubbs R . Synthesis and activity of a new generation of ruthenium-based olefin metathesis catalysts coordinated with 1,3-dimesityl-4,5-dihydroimidazol-2-ylidene ligands. Org Lett. 2000; 1(6):953-6. DOI: 10.1021/ol990909q. View

Trnka T, Grubbs R . The development of L2X2Ru=CHR olefin metathesis catalysts: an organometallic success story. Acc Chem Res. 2001; 34(1):18-29. DOI: 10.1021/ar000114f. View

Mayo K, Nearhoof E, Kiddle J . Microwave-accelerated ruthenium-catalyzed olefin metathesis. Org Lett. 2002; 4(9):1567-70. DOI: 10.1021/ol025789s. View

Fodje M, Al-Karadaghi S . Occurrence, conformational features and amino acid propensities for the pi-helix. Protein Eng. 2002; 15(5):353-8. DOI: 10.1093/protein/15.5.353. View

Wakamatsu H, Blechert S . A highly active and air-stable ruthenium complex for olefin metathesis. Angew Chem Int Ed Engl. 2002; 41(5):794-6. DOI: 10.1002/1521-3773(20020301)41:5<794::aid-anie794>3.0.co;2-b. View

Armen R, Alonso D, Daggett V . The role of alpha-, 3(10)-, and pi-helix in helix-->coil transitions. Protein Sci. 2003; 12(6):1145-57. PMC: 2323891. DOI: 10.1110/ps.0240103. View

Meutermans W, Bourne G, Golding S, Horton D, Campitelli M, Craik D . Difficult macrocyclizations: new strategies for synthesizing highly strained cyclic tetrapeptides. Org Lett. 2003; 5(15):2711-4. DOI: 10.1021/ol034907o. View

Garbacia S, Desai B, Lavastre O, Kappe C . Microwave-assisted ring-closing metathesis revisited. On the question of the nonthermal microwave effect. J Org Chem. 2003; 68(23):9136-9. DOI: 10.1021/jo035135c. View

Hoveyda A, Gillingham D, Van Veldhuizen J, Kataoka O, Garber S, Kingsbury J . Ru complexes bearing bidentate carbenes: from innocent curiosity to uniquely effective catalysts for olefin metathesis. Org Biomol Chem. 2004; 2(1):8-23. DOI: 10.1039/b311496c. View

10.

Chapman R, Dimartino G, Arora P . A highly stable short alpha-helix constrained by a main-chain hydrogen-bond surrogate. J Am Chem Soc. 2004; 126(39):12252-3. DOI: 10.1021/ja0466659. View

11.

Kappe C . Controlled microwave heating in modern organic synthesis. Angew Chem Int Ed Engl. 2004; 43(46):6250-84. DOI: 10.1002/anie.200400655. View

12.

Shepherd N, Hoang H, Abbenante G, Fairlie D . Single turn peptide alpha helices with exceptional stability in water. J Am Chem Soc. 2005; 127(9):2974-83. DOI: 10.1021/ja0456003. View

13.

Dimartino G, Wang D, Chapman R, Arora P . Solid-phase synthesis of hydrogen-bond surrogate-derived alpha-helices. Org Lett. 2005; 7(12):2389-92. DOI: 10.1021/ol0506516. View

14.

Murray J, Farooqi B, Sadowsky J, Scalf M, Freund W, Smith L . Efficient synthesis of a beta-peptide combinatorial library with microwave irradiation. J Am Chem Soc. 2005; 127(38):13271-80. DOI: 10.1021/ja052733v. View

15.

Bock V, Perciaccante R, Jansen T, Hiemstra H, van Maarseveen J . Click chemistry as a route to cyclic tetrapeptide analogues: synthesis of cyclo-[Pro-Val-psi(triazole)-Pro-Tyr]. Org Lett. 2006; 8(5):919-22. DOI: 10.1021/ol053095o. View

16.

Wang D, Chen K, Kulp Iii J, Arora P . Evaluation of biologically relevant short alpha-helices stabilized by a main-chain hydrogen-bond surrogate. J Am Chem Soc. 2006; 128(28):9248-56. PMC: 1828873. DOI: 10.1021/ja062710w. View

17.

Blackwell H, Grubbs R . Highly Efficient Synthesis of Covalently Cross-Linked Peptide Helices by Ring-Closing Metathesis. Angew Chem Int Ed Engl. 2018; 37(23):3281-3284. DOI: 10.1002/(SICI)1521-3773(19981217)37:23<3281::AID-ANIE3281>3.0.CO;2-V. View