Ring-Closing Metathesis Approaches Towards the Total Synthesis of Rhizoxins

Overview

Journal Molecules

Publisher MDPI

Specialty Biology

Date 2020 Oct 7

PMID 33023218

Citations 4

Authors

Marc Liniger

Christian M Neuhaus

Karl-Heinz Altmann

Affiliations

Soon will be listed here.

Abstract

Efforts are described towards the total synthesis of the bacterial macrolide rhizoxin F, which is a potent tubulin assembly and cancer cell growth inhibitor. A significant amount of work was expanded on the construction of the rhizoxin core macrocycle by ring-closing olefin metathesis (RCM) between C(9) and C(10), either directly or by using relay substrates, but in no case was ring-closure achieved. Macrocycle formation was possible by ring-closing alkyne metathesis (RCAM) at the C(9)/C(10) site. The requisite diyne was obtained from advanced intermediates that had been prepared as part of the synthesis of the RCM substrates. While the direct conversion of the triple bond formed in the ring-closing step into the C(9)-C(10) double bond of the rhizoxin macrocycle proved to be elusive, the corresponding Z isomer was accessible with high selectivity by reductive decomplexation of the biscobalt hexacarbonyl complex of the triple bond with ethylpiperidinium hypophosphite. Radical-induced double bond isomerization, full elaboration of the C(15) side chain, and directed epoxidation of the C(11)-C(12) double bond completed the total synthesis of rhizoxin F.

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References

Takahashi M, Matsumoto S, Iwasaki S, YAHARA I . Molecular basis for determining the sensitivity of eucaryotes to the antimitotic drug rhizoxin. Mol Gen Genet. 1990; 222(2-3):169-75. DOI: 10.1007/BF00633814. View

Brendel N, Partida-Martinez L, Scherlach K, Hertweck C . A cryptic PKS-NRPS gene locus in the plant commensal Pseudomonas fluorescens Pf-5 codes for the biosynthesis of an antimitotic rhizoxin complex. Org Biomol Chem. 2007; 5(14):2211-3. DOI: 10.1039/b707762a. View

Takahashi M, Iwasaki S, Kobayashi H, Okuda S, Murai T, Sato Y . Rhizoxin binding to tubulin at the maytansine-binding site. Biochim Biophys Acta. 1987; 926(3):215-23. DOI: 10.1016/0304-4165(87)90206-6. View

Trost B, Ball Z . Alkyne hydrosilylation catalyzed by a cationic ruthenium complex: efficient and general trans addition. J Am Chem Soc. 2005; 127(50):17644-55. PMC: 2532823. DOI: 10.1021/ja0528580. View

Loper J, Henkels M, Rangel L, Olcott M, Walker F, Bond K . Rhizoxin analogs, orfamide A and chitinase production contribute to the toxicity of Pseudomonas protegens strain Pf-5 to Drosophila melanogaster. Environ Microbiol. 2016; 18(10):3509-3521. DOI: 10.1111/1462-2920.13369. View

Lebel H, Paquet V . Rhodium-catalyzed methylenation of aldehydes. J Am Chem Soc. 2004; 126(1):320-8. DOI: 10.1021/ja038112o. View

Kwon Y, Schulthoff S, Dao Q, Wirtz C, Furstner A . Total Synthesis of Disciformycin A and B: Unusually Exigent Targets of Biological Significance. Chemistry. 2017; 24(1):109-114. DOI: 10.1002/chem.201705550. View

Smith A, Sfouggatakis C, Risatti C, Sperry J, Zhu W, Doughty V . Spongipyran Synthetic Studies. Evolution of a Scalable Total Synthesis of (+)-Spongistatin 1. Tetrahedron. 2010; 65(33):6489-6509. PMC: 2902791. DOI: 10.1016/j.tet.2009.04.003. View

Hendriks H, Plowman J, Berger D, Paull K, Fiebig H, Fodstad O . Preclinical antitumour activity and animal toxicology studies of rhizoxin, a novel tubulin-interacting agent. Ann Oncol. 1992; 3(9):755-63. DOI: 10.1093/oxfordjournals.annonc.a058334. View

10.

Neuhaus C, Liniger M, Stieger M, Altmann K . Total synthesis of the tubulin inhibitor WF-1360F based on macrocycle formation through ring-closing alkyne metathesis. Angew Chem Int Ed Engl. 2013; 52(22):5866-70. DOI: 10.1002/anie.201300576. View

11.

Williams D, Meyer K . Total synthesis of (+)-amphidinolide K. J Am Chem Soc. 2001; 123(4):765-6. DOI: 10.1021/ja005644l. View

12.

Menche D, Hassfeld J, Li J, Rudolph S . Total synthesis of archazolid A. J Am Chem Soc. 2007; 129(19):6100-1. DOI: 10.1021/ja071461o. View

13.

Willwacher J, Kausch-Busies N, Furstner A . Divergent total synthesis of the antimitotic agent leiodermatolide. Angew Chem Int Ed Engl. 2012; 51(48):12041-6. DOI: 10.1002/anie.201206670. View

14.

Iwasaki S, Kobayashi H, Furukawa J, Namikoshi M, Okuda S, SATO Z . Studies on macrocyclic lactone antibiotics. VII. Structure of a phytotoxin "rhizoxin" produced by Rhizopus chinensis. J Antibiot (Tokyo). 1984; 37(4):354-62. DOI: 10.7164/antibiotics.37.354. View

15.

Tsuruo T, Iida H, Tsukagoshi S, SATO Z, Matsuda I, Iwasaki S . Rhizoxin, a macrocyclic lactone antibiotic, as a new antitumor agent against human and murine tumor cells and their vincristine-resistant sublines. Cancer Res. 1986; 46(1):381-5. View

16.

Micoine K, Furstner A . Concise total synthesis of the potent translation and cell migration inhibitor lactimidomycin. J Am Chem Soc. 2010; 132(40):14064-6. DOI: 10.1021/ja107141p. View

17.

Poon K, Dudley G . Mix-and-heat benzylation of alcohols using a bench-stable pyridinium salt. J Org Chem. 2006; 71(10):3923-7. DOI: 10.1021/jo0602773. View

18.

Brewitz L, Llaveria J, Yada A, Furstner A . Formal total synthesis of the algal toxin (-)-polycavernoside A. Chemistry. 2013; 19(14):4532-7. DOI: 10.1002/chem.201204551. View

19.

White J, Blakemore P, Green N, Hauser E, Holoboski M, Keown L . Total synthesis of rhizoxin D, a potent antimitotic agent from the fungus Rhizopus chinensis. J Org Chem. 2002; 67(22):7750-60. DOI: 10.1021/jo020537q. View

20.

Kusebauch B, Scherlach K, Kirchner H, Dahse H, Hertweck C . Antiproliferative effects of ester- and amide-functionalized rhizoxin derivatives. ChemMedChem. 2011; 6(11):1998-2001. DOI: 10.1002/cmdc.201100319. View