Studies Targeting Ryanodol Result in an Annulation Reaction for the Synthesis of a Variety of Fused Carbocycles

Overview

Journal Org Lett

Publisher American Chemical Society

Specialties Biochemistry
Chemistry

Date 2019 Jul 13

PMID 31298546

Citations 2

Authors

Rajdip Karmakar

Arnold L Rheingold

Glenn C Micalizio

Affiliations

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Abstract

An annulation reaction is described to access a range of polycyclic and highly oxygenated carbocycles. First developed in an approach to the synthesis of ryanodol, metallacycle-mediated annulative diketone-alkyne coupling defines a framework for realization of new retrosynthetic relationships for complex molecule synthesis. In addition to demonstrating this reaction in the context of forging distinct carbocyclic systems, including those featuring a seven-membered ring, the choice of quenching reagent leads to unique reaction outcomes.

Citing Articles

Recent Advances in Construction of Polycyclic Natural Product Scaffolds via One-Pot Reactions Involving Alkyne Annulation.

Zheng L, Hua R Front Chem. 2020; 8:580355.

PMID: 33195069 PMC: 7596902. DOI: 10.3389/fchem.2020.580355.

Synthesis of Anhydroryanodol.

Du K, Kier M, Stempel Z, Jeso V, Rheingold A, Micalizio G J Am Chem Soc. 2020; 142(30):12937-12941.

PMID: 32609506 PMC: 7477650. DOI: 10.1021/jacs.0c05766.

References

Nicolaou , Vourloumis , Winssinger , Baran . The Art and Science of Total Synthesis at the Dawn of the Twenty-First Century. Angew Chem Int Ed Engl. 2000; 39(1):44-122. View

Maier . Synthesis of Medium-Sized Rings by the Ring-Closing Metathesis Reaction. Angew Chem Int Ed Engl. 2000; 39(12):2073-2077. DOI: 10.1002/1521-3773(20000616)39:12<2073::aid-anie2073>3.0.co;2-0. View

Yet L . Metal-mediated synthesis of medium-sized rings. Chem Rev. 2001; 100(8):2963-3008. DOI: 10.1021/cr990407q. View

Fill M, Copello J . Ryanodine receptor calcium release channels. Physiol Rev. 2002; 82(4):893-922. DOI: 10.1152/physrev.00013.2002. View

Watson I, Ritter S, Toste F . Asymmetric synthesis of medium-sized rings by intramolecular Au(I)-catalyzed cyclopropanation. J Am Chem Soc. 2009; 131(6):2056-7. PMC: 2662771. DOI: 10.1021/ja8085005. View

McCauley M, Wehrens X . Targeting ryanodine receptors for anti-arrhythmic therapy. Acta Pharmacol Sin. 2011; 32(6):749-57. PMC: 4009959. DOI: 10.1038/aps.2011.44. View

Nicolaou K, Hale C, Nilewski C, Ioannidou H . Constructing molecular complexity and diversity: total synthesis of natural products of biological and medicinal importance. Chem Soc Rev. 2012; 41(15):5185-238. PMC: 3426871. DOI: 10.1039/c2cs35116a. View

Hoffmann R . Natural product synthesis: changes over time. Angew Chem Int Ed Engl. 2012; 52(1):123-30. DOI: 10.1002/anie.201203319. View

Kuttruff C, Eastgate M, Baran P . Natural product synthesis in the age of scalability. Nat Prod Rep. 2013; 31(4):419-32. DOI: 10.1039/c3np70090a. View

10.

Waterhouse A, Pessah I, Francini A, Casida J . Structural aspects of ryanodine action and selectivity. J Med Chem. 1987; 30(4):710-6. DOI: 10.1021/jm00387a022. View

11.

Mulzer J . Trying to rationalize total synthesis. Nat Prod Rep. 2014; 31(4):595-603. DOI: 10.1039/c3np70105k. View

12.

Nagatomo M, Koshimizu M, Masuda K, Tabuchi T, Urabe D, Inoue M . Total synthesis of ryanodol. J Am Chem Soc. 2014; 136(16):5916-9. DOI: 10.1021/ja502770n. View

13.

Masuda K, Koshimizu M, Nagatomo M, Inoue M . Asymmetric Total Synthesis of (+)-Ryanodol and (+)-Ryanodine. Chemistry. 2015; 22(1):230-6. DOI: 10.1002/chem.201503641. View

14.

Chuang K, Xu C, Reisman S . A 15-step synthesis of (+)-ryanodol. Science. 2016; 353(6302):912-5. PMC: 5505075. DOI: 10.1126/science.aag1028. View

15.

Xu C, Han A, Virgil S, Reisman S . Chemical Synthesis of (+)-Ryanodine and (+)-20-Deoxyspiganthine. ACS Cent Sci. 2017; 3(4):278-282. PMC: 5409222. DOI: 10.1021/acscentsci.6b00361. View

16.

Zweig J, Kim D, Newhouse T . Methods Utilizing First-Row Transition Metals in Natural Product Total Synthesis. Chem Rev. 2017; 117(18):11680-11752. DOI: 10.1021/acs.chemrev.6b00833. View

17.

Kier M, Leon R, ORourke N, Rheingold A, Micalizio G . Synthesis of Highly Oxygenated Carbocycles by Stereoselective Coupling of Alkynes to 1,3- and 1,4-Dicarbonyl Systems. J Am Chem Soc. 2017; 139(36):12374-12377. PMC: 5600187. DOI: 10.1021/jacs.7b06286. View

18.

Du K, Kier M, Rheingold A, Micalizio G . Toward the Total Synthesis of Ryanodol via Oxidative Alkyne-1,3-Diketone Annulation: Construction of a Ryanoid Tetracycle. Org Lett. 2018; 20(20):6457-6461. PMC: 6199674. DOI: 10.1021/acs.orglett.8b02767. View

19.

Millham A, Kier M, Leon R, Karmakar R, Stempel Z, Micalizio G . A Complementary Process to Pauson-Khand-Type Annulation Reactions for the Construction of Fully Substituted Cyclopentenones. Org Lett. 2019; 21(2):567-570. PMC: 6465167. DOI: 10.1021/acs.orglett.8b03922. View

20.

JENDEN D, Fairhurst A . The pharmacology of ryanodine. Pharmacol Rev. 1969; 21(1):1-25. View