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Sulfamate-tethered aza-Wacker approach towards analogs of Bactobolin A

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Abstract

Here, we describe an approach towards analogs of the potent antibiotic Bactobolin A. Sulfamate-tethered aza-Wacker cyclization reactions furnish key synthons, which we envision can be elaborated into analogs of Bactobolin A. Docking studies show that the C4 epimer of Bactobolin A and the C4/C6 diastereomer interact with different residues of the 23S rRNA (bacterial ribosome 50S subunit) than the natural product, suggesting that these molecules could be valuable tool compounds for fundamental studies of the bacterial translational machinery.

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References

  1. Baran PS. Natural product total synthesis: as exciting as ever and here to stay. J Am Chem Soc. 2018;140:4751–5. https://doi.org/10.1021/jacs.8b02266.

    Article  CAS  PubMed  Google Scholar 

  2. Denmark SE. Organic synthesis: wherefrom and whither? (Some very personal reflections). Isr J Chem. 2018;58:61–72. https://doi.org/10.1002/ijch.201700085.

    Article  CAS  PubMed  Google Scholar 

  3. Wender PA. Toward the ideal synthesis and molecular function through synthesis-informed design. Nat Prod Rep. 2014;31:433–40. https://doi.org/10.1039/C4NP00013G.

    Article  CAS  Google Scholar 

  4. Shinde AH, Sathyamoorthi S. Oxidative cyclization of sulfamates onto pendant alkenes. Org Lett. 2020;22:896–901. https://doi.org/10.1021/acs.orglett.9b04448.

    Article  CAS  PubMed  Google Scholar 

  5. Shinde AH, Nagamalla S, Sathyamoorthi S. N-arylated oxathiazinane heterocycles are convenient synthons for 1,3-amino ethers and 1,3-amino thioethers. Medicinal Chem Res. 2020;29:1223–9. https://doi.org/10.1007/s00044-020-02556-x.

    Article  CAS  Google Scholar 

  6. Thomas AA, Nagamalla S, Sathyamoorthi S. Salient features of the aza-Wacker cyclization reaction. Chem Sci. 2020;11:8073–88. https://doi.org/10.1039/D0SC02554B.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Shinde AH, Sathyamoorthi S. Tethered silanoxymercuration of allylic alcohols. Org Lett. 2020;22:8665–9. https://doi.org/10.1021/acs.orglett.0c03257.

    Article  CAS  PubMed  Google Scholar 

  8. Kondo S, Horiuchi Y, Hamada M, Takeuchi T, Umezawa H. A new antitumor antibiotic, bactobolin produced by pseudomonas. J Antibiot. 1979;32:1069–71.

    Article  CAS  Google Scholar 

  9. Chandler JR, Truong TT, Silva PM, Seyedsayamdost MR, Carr G, Radey M, et al. Bactobolin resistance is conferred by mutations in the L2 ribosomal protein. mBio. 2012;3:e00499–12. https://doi.org/10.1128/mBio.00499-12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Seyedsayamdost MR, Chandler JR, Blodgett JAV, Lima PS, Duerkop BA, Oinuma K-I, et al. Quorum-sensing-regulated bactobolin production by Burkholderia thailandensis E264. Org Lett. 2010;12:716–9. https://doi.org/10.1021/ol902751x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Klaus JR, Coulon PML, Koirala P, Seyedsayamdost MR, Déziel E, Chandler JR. Secondary metabolites from the Burkholderia pseudomallei complex: structure, ecology, and evolution. J Ind Microbiol Biotechnol. 2020;47:877–87. https://doi.org/10.1007/s10295-020-02317-0.

    Article  CAS  PubMed  Google Scholar 

  12. Munakata T, Okumoto T. Some structure-activity relationships for bactobolin analogs in the treatment of mouse leukemia P388. Chem Pharm Bull. 1981;29:891–4. https://doi.org/10.1248/cpb.29.891.

    Article  CAS  Google Scholar 

  13. Okumoto T, Kontani M, Hoshino H, Nakanishi M. Antitumor activity of newly isolated antibiotics, 3-dichloromethylactinobolins. J Pharmacobio-Dyn. 1980;3:177–82. https://doi.org/10.1248/bpb1978.3.177.

    Article  CAS  PubMed  Google Scholar 

  14. Greenberg EP, Chandler JR, Seyedsayamdost MR. The chemistry and biology of bactobolin: a 10-year collaboration with natural product chemist extraordinaire jon clardy. J Nat Prod. 2020;83:738–43. https://doi.org/10.1021/acs.jnatprod.9b01237.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Amunts A, Fiedorczuk K, Truong TT, Chandler J, Greenberg EP, Ramakrishnan V. Bactobolin A binds to a site on the 70S ribosome distinct from previously seen antibiotics. J Mol Biol. 2015;427:753–5. https://doi.org/10.1016/j.jmb.2014.12.018.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Garigipati RS, Tschaen DM, Weinreb SM. Stereoselective total syntheses of the antitumor antibiotics (+)-actinobolin and (−)-bactobolin from a common bridged lactone intermediate. J Am Chem Soc. 1990;112:3475–82. https://doi.org/10.1021/ja00165a035.

    Article  CAS  Google Scholar 

  17. Weinreb SM, Garigipati RS. Design of an efficient strategy for total synthesis of the microbial metabolite (−)-bactobolin. Pure Appl Chem. 1989;61:435

    Article  CAS  Google Scholar 

  18. Garigipati RS, Weinreb SM. Stereoselective total synthesis of the antitumor antibiotic (−)-bactobolin. J Org Chem. 1988;53:4143–5. https://doi.org/10.1021/jo00252a060.

    Article  CAS  Google Scholar 

  19. Vojackova P, Michalska L, Necas M, Shcherbakov D, Bottger EC, Sponer J, et al. Stereocontrolled synthesis of (−)-Bactobolin A. J Am Chem Soc. 2020;142:7306–11. https://doi.org/10.1021/jacs.0c01554.

    Article  CAS  PubMed  Google Scholar 

  20. Askin D, Angst C, Danishefsky S. An approach to the synthesis of bactobolin and the total synthesis of N-acetylactinobolamine: some remarkably stable hemiacetals. J Org Chem. 1987;52:622–35. https://doi.org/10.1021/jo00380a025.

    Article  CAS  Google Scholar 

  21. Ward DE, Gai Y, Kaller BF.Synthetic studies on actinobolin and bactobolin: synthesis of N-Desalanyl-N-[2-(trimethylsilyl)ethanesulfonyl] derivatives from a common intermediate and attempted removal of the SES protecting group.J Organic Chem.1996;61:5498–505. https://doi.org/10.1021/jo960579c.

    Article  CAS  Google Scholar 

  22. Ward DE, Gai Y, Kaller BF. Synthesis of (−)-bactobolin from D-glucose and from (+)-actinobolin. Tetrahedron Lett. 1994;35:3485–8. https://doi.org/10.1016/S0040-4039(00)73216-3.

    Article  CAS  Google Scholar 

  23. Underwood R, Fraser-Reid B. Support studies for the conversion of actinobolin into bactobolin. J Chem Soc Perkin Trans 1. 1990:731–8. https://doi.org/10.1039/P19900000731.

  24. Adachi H, Nishimura Y, Takeuchi T. Synthesis and activities of bactobolin derivatives having new functionality at C-3. J Antibiot. 2009;55:92–8.

    Article  Google Scholar 

  25. Adachi H, Nishimura Y. Synthesis and biological activity of bactobolin glucosides. Nat Prod Res. 2003;17:253–7. https://doi.org/10.1080/1057563021000060112.

    Article  CAS  PubMed  Google Scholar 

  26. Adachi H, Usui T, Nishimura Y, Kondo S, Ishizuka M, Takeuchi T. Synthesis and activities of bactobolin derivatives based on the alteration of the functionality at C-3 position. J Antibiot. 1998;51:184–8.

    Article  CAS  Google Scholar 

  27. Kotov V, Scarborough CC, Stahl SS. Palladium-catalyzed aerobic oxidative amination of alkenes: development of intra- and intermolecular aza-Wacker reactions. Inorg Chem. 2007;46:1910–23. https://doi.org/10.1021/ic061997v.

    Article  CAS  PubMed  Google Scholar 

  28. Wang D, Weinstein AB, White PB, Stahl SS. Ligand-promoted palladium-catalyzed aerobic oxidation reactions. Chem Rev. 2018;118:2636–79. https://doi.org/10.1021/acs.chemrev.7b00334.

    Article  CAS  PubMed  Google Scholar 

  29. Wang Z-X, Miller SM, Anderson OP, Shi Y. A class of C2 and pseudo C2 symmetric ketone catalysts for asymmetric epoxidation. Conformational effect on catalysis. J Org Chem. 1999;64:6443–58. https://doi.org/10.1021/jo9908849.

    Article  CAS  Google Scholar 

  30. Kawashima H, Sakai M, Kaneko Y, Kobayashi Y. Further study on synthesis of the cyclobakuchiols. Tetrahedron. 2015;71:2387–92. https://doi.org/10.1016/j.tet.2015.02.092.

    Article  CAS  Google Scholar 

  31. Espino CG, Wehn PM, Chow J, Du Bois J. Synthesis of 1,3-difunctionalized amine derivatives through selective C−H bond oxidation. J Am Chem Soc. 2001;123:6935–6. https://doi.org/10.1021/ja011033x.

    Article  CAS  Google Scholar 

  32. Swamy KCK, Kumar NNB, Balaraman E, Kumar KVPP. Mitsunobu and related reactions: advances and applications. Chem Rev. 2009;109:2551–651. https://doi.org/10.1021/cr800278z.

    Article  CAS  PubMed  Google Scholar 

  33. Takaya J, Kagoshima H, Akiyama T. Mannich-type reaction with trifluoromethylated N,O-hemiacetal: facile preparation of β-amino-β-trifluoromethyl carbonyl compounds. Org Lett. 2000;2:1577–9. https://doi.org/10.1021/ol005812e.

    Article  CAS  PubMed  Google Scholar 

  34. Fustero S, Soler JG, Bartolomé A, Roselló MS. Novel approach for asymmetric synthesis of fluorinated β-amino sulfones and allylic amines. Org Lett. 2003;5:2707–10. https://doi.org/10.1021/ol034892u.

    Article  CAS  PubMed  Google Scholar 

  35. Kronenthal DR, Han CY, Taylor MK. Oxidative N-dearylation of 2-azetidinones. p-Anisidine as a source of azetidinone nitrogen. J Org Chem. 1982;47:2765–8. https://doi.org/10.1021/jo00135a016.

    Article  CAS  Google Scholar 

  36. Ha D-C, Hart DJ. Syntheses of methyl N-benzoylacosaminide and methyl N-(benzyloxyoxalyl)-daunosaminide from (S)-ethyl 3-hydroxybutyrate. Tetrahedron Lett. 1987;28:4489–92. https://doi.org/10.1016/S0040-4039(00)96544-4.

  37. Madhavi Sastry G, Adzhigirey M, Day T, Annabhimoju R, Sherman W. Protein and ligand preparation: parameters, protocols, and influence on virtual screening enrichments. J Comput Aided Mol Des. 2013;27:221–34. https://doi.org/10.1007/s10822-013-9644-8.

    Article  CAS  PubMed  Google Scholar 

  38. Friesner RA, Banks JL, Murphy RB, Halgren TA, Klicic JJ, Mainz DT, et al. Glide: a new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy. J Med Chem. 2004;47:1739–49. https://doi.org/10.1021/jm0306430.

    Article  CAS  PubMed  Google Scholar 

  39. Friesner RA, Murphy RB, Repasky MP, Frye LL, Greenwood JR, Halgren TA, et al. Extra precision glide: docking and scoring incorporating a model of hydrophobic enclosure for protein−ligand complexes. J Med Chem. 2006;49:6177–96. https://doi.org/10.1021/jm051256o.

    Article  CAS  PubMed  Google Scholar 

  40. Halgren TA, Murphy RB, Friesner RA, Beard HS, Frye LL, Pollard WT, et al. Glide: a new approach for rapid, accurate docking and scoring. 2. Enrichment factors in database screening. J Med Chem. 2004;47:1750–9. https://doi.org/10.1021/jm030644s.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This work was supported by start-up funding provided jointly by the University of Kansas Office of the Provost and the Department of Medicinal Chemistry as well as an NIH COBRE Chemical Biology of Infectious Diseases Research Project Grant to S.S. (P20GM113117). We thank Dr. Victor Day (University of Kansas) for X-ray crystallography analysis. Funding for the X-ray diffractometer was provided by an NSF-MRI grant (CHE-0923449).

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  1. Department of Medicinal Chemistry, University of Kansas, Lawrence, KS, 66047, USA

    Someshwar Nagamalla, David K. Johnson & Shyam Sathyamoorthi

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  1. Someshwar Nagamalla
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Nagamalla, S., Johnson, D.K. & Sathyamoorthi, S. Sulfamate-tethered aza-Wacker approach towards analogs of Bactobolin A. Med Chem Res 30, 1348–1357 (2021). https://doi.org/10.1007/s00044-021-02724-7

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