A "methyl Extension" Strategy for Polyketide Natural Product Linker Site Validation and Its Application to Dictyostatin

Overview

Journal J Am Chem Soc

Publisher American Chemical Society

Specialty Chemistry

Date 2015 Nov 3

PMID 26522184

Citations 5

Authors

Stephen Ho

Dan L Sackett

James L Leighton

Affiliations

Soon will be listed here.

Abstract

An approach to the validation of linker strategies for polyketide natural products with few or no obvious handles for linker attachment, and its application to dictyostatin, are described. Analogues in which the C(6)- and C(12)-methyl groups were replaced by 4-azidobutyl groups were prepared and shown to retain the low nanomolar potency of dictyostatin. Further, conjugation of the C(6) analogue with a cyclooctyne resulted in only minor attenuations in potency. Together, these results shed light on the binding of dictyostatin to β-tubulin, establish a validated linker strategy for dictyostatin, and set the stage for the synthesis and study of dictyostatin conjugates.

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References

Nilsson B, Kiessling L, Raines R . Staudinger ligation: a peptide from a thioester and azide. Org Lett. 2000; 2(13):1939-41. DOI: 10.1021/ol0060174. View

SAXON E, Armstrong J, Bertozzi C . A "traceless" Staudinger ligation for the chemoselective synthesis of amide bonds. Org Lett. 2000; 2(14):2141-3. DOI: 10.1021/ol006054v. View

Goldberg S, Grubbs R . A one-pot cross-metathesis/allylboration reaction: a three-component coupling for the synthesis of functionalized homoallylic alcohols. Angew Chem Int Ed Engl. 2002; 41(5):807-10. DOI: 10.1002/1521-3773(20020301)41:5<807::aid-anie807>3.0.co;2-v. View

Isbrucker R, Cummins J, Pomponi S, Longley R, Wright A . Tubulin polymerizing activity of dictyostatin-1, a polyketide of marine sponge origin. Biochem Pharmacol. 2003; 66(1):75-82. DOI: 10.1016/s0006-2952(03)00192-8. View

Paterson I, Britton R, Delgado O, Wright A . Stereochemical determination of dictyostatin, a novel microtubule-stabilising macrolide from the marine sponge Corallistidae sp. Chem Commun (Camb). 2004; (6):632-3. DOI: 10.1039/b316390c. View

Shiina I, Kubota M, Oshiumi H, Hashizume M . An effective use of benzoic anhydride and its derivatives for the synthesis of carboxylic esters and lactones: a powerful and convenient mixed anhydride method promoted by basic catalysts. J Org Chem. 2004; 69(6):1822-30. DOI: 10.1021/jo030367x. View

Agard N, Prescher J, Bertozzi C . A strain-promoted [3 + 2] azide-alkyne cycloaddition for covalent modification of biomolecules in living systems. J Am Chem Soc. 2004; 126(46):15046-7. DOI: 10.1021/ja044996f. View

Fukui Y, Bruckner A, Shin Y, Balachandran R, Day B, Curran D . Fluorous mixture synthesis of (-)-dictyostatin and three stereoisomers. Org Lett. 2006; 8(2):301-4. DOI: 10.1021/ol0526827. View

Paterson I, Gardner N, Poullennec K, Wright A . Synthesis and biological evaluation of novel analogues of dictyostatin. Bioorg Med Chem Lett. 2007; 17(9):2443-7. DOI: 10.1016/j.bmcl.2007.02.031. View

10.

Jung W, Harrison C, Shin Y, Fournier J, Balachandran R, Raccor B . Total synthesis and biological evaluation of C16 analogs of (-)-dictyostatin. J Med Chem. 2007; 50(13):2951-66. DOI: 10.1021/jm061385k. View

11.

Lutz J . Copper-free azide-alkyne cycloadditions: new insights and perspectives. Angew Chem Int Ed Engl. 2008; 47(12):2182-4. DOI: 10.1002/anie.200705365. View

12.

Huber J, Perl N, Leighton J . Allylsilane-vinylarene cross-metathesis enables a powerful approach to enantioselective imine allylation. Angew Chem Int Ed Engl. 2008; 47(16):3037-9. DOI: 10.1002/anie.200705621. View

13.

Canales A, Matesanz R, Gardner N, Andreu J, Paterson I, Fernando Diaz J . The bound conformation of microtubule-stabilizing agents: NMR insights into the bioactive 3D structure of discodermolide and dictyostatin. Chemistry. 2008; 14(25):7557-69. DOI: 10.1002/chem.200800039. View

14.

Shin Y, Fournier J, Bruckner A, Madiraju C, Balachandran R, Raccor B . Synthesis and biological evaluation of (-)-dictyostatin and stereoisomers. Tetrahedron. 2008; 63(35):8537-8562. PMC: 2000856. DOI: 10.1016/j.tet.2007.05.033. View

15.

Paterson I, Gardner N, Guzman E, Wright A . Total synthesis and biological evaluation of novel C2-C6 region analogues of dictyostatin. Bioorg Med Chem. 2008; 17(6):2282-9. DOI: 10.1016/j.bmc.2008.10.084. View

16.

Ducry L, Stump B . Antibody-drug conjugates: linking cytotoxic payloads to monoclonal antibodies. Bioconjug Chem. 2009; 21(1):5-13. DOI: 10.1021/bc9002019. View

17.

Zhu W, Jimenez M, Jung W, Camarco D, Balachandran R, Vogt A . Streamlined syntheses of (-)-dictyostatin, 16-desmethyl-25,26-dihydrodictyostatin, and 6-epi-16-desmethyl-25,26-dihydrodictyostatin. J Am Chem Soc. 2010; 132(26):9175-87. PMC: 2903049. DOI: 10.1021/ja103537u. View

18.

Dommerholt J, Schmidt S, Temming R, Hendriks L, Rutjes F, van Hest J . Readily accessible bicyclononynes for bioorthogonal labeling and three-dimensional imaging of living cells. Angew Chem Int Ed Engl. 2010; 49(49):9422-5. PMC: 3021724. DOI: 10.1002/anie.201003761. View

19.

Paterson I, Naylor G, Gardner N, Guzman E, Wright A . Total synthesis and biological evaluation of a series of macrocyclic hybrids and analogues of the antimitotic natural products dictyostatin, discodermolide, and taxol. Chem Asian J. 2011; 6(2):459-73. PMC: 3050503. DOI: 10.1002/asia.201000541. View

20.

Jogalekar A, Damodaran K, Kriel F, Jung W, Alcaraz A, Zhong S . Dictyostatin flexibility bridges conformations in solution and in the β-tubulin taxane binding site. J Am Chem Soc. 2011; 133(8):2427-36. DOI: 10.1021/ja1023817. View