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Molecular Diversity

, Volume 18, Issue 4, pp 701–719 | Cite as

Catalytic enantioselective diversity-oriented synthesis of a small library of polyhydroxylated pyrans inspired from thiomarinol antibiotics

  • Raed M. Al-Zoubi
  • Dennis G. Hall
Full-Length Paper

Abstract

A small library of 30 thiomarinol analogues was successfully synthesised using as a key step–a catalytic enantioselective tandem oxa[4+2] cycloaddition/aldehyde allylboration methodology. With this method, highly substituted \(\alpha \)-hydroxyalkyl dihydropyrans were assembled in a single three-component reaction utilizing three different enol ethers and a wide variety of aldehydes, such as aromatic, heteroaromatic, unsaturated and aliphatic aldehydes. In a second operation, a mild and direct method for reducing an acetal unit in the \(\alpha \)-hydroxyalkyl dihydropyrans was optimised without the need for protecting a nearby hydroxyl group. This procedure facilitated the synthetic sequence, which was completed by a dihydroxylation of the residual olefin of \(\alpha \)-hydroxyalkyl 2\(H\)-pyrans to provide the desired library of dihydroxylated pyran analogues reminiscent of the thiomarinol antibiotics. The relative stereochemistry of the resulting library compounds was demonstrated by X-ray crystallography on one of the analogues.

Graphical Abstract

Keywords

Allylboration ATP mimics Combinatorial library  Enantioselective catalysis Hetero-Diels–Alder cycloaddition Pyrans 

Notes

Acknowledgments

The authors thank the Natural Sciences and Engineering Research Council (NSERC) of Canada and the University of Alberta for financial support of this research.

Supplementary material

11030_2014_9542_MOESM1_ESM.pdf (18.6 mb)
ESM 1 (PDF 19,012 kb)

References

  1. 1.
    Sutherland R, Boon RJ, Griffin KE, Masters PJ, Slocombe B, White AR (1985) Antibacterial activity of mupirocin (pseudomonic acid), a new antibiotic for topical use. Antimicrob Agents Chemother 27:495–498PubMedCrossRefPubMedCentralGoogle Scholar
  2. 2.
    Badder A, Garre C (1887) Title. Corresp Bl Sweiz Aertze 17:385Google Scholar
  3. 3.
    Fuller AT, Mellows G, Woolford M, Banks GT, Barrow KD, Chain EB (1971) Pseudomonic acid—antibiotic produced by Pseudomonas fluorescens. Nature 234:416–416. doi: 10.1038/234416a0 PubMedCrossRefGoogle Scholar
  4. 4.
    Chain EB, Mellows G (1977) Pseudomonic acid. 3. Structure of pseudomonic acid B. J Chem Soc Perkin Trans 1:318–322. doi: 10.1039/p19770000318 CrossRefGoogle Scholar
  5. 5.
    Alexander RG, Clayton JP, Luk K, Rogers NH, King TJ (1978) Chemistry of pseudomonic acid. 1. Absolute configuration of pseudomonic acid A. J Chem Soc Perkin Trans 1:561–565. doi: 10.1039/p19780000561 CrossRefGoogle Scholar
  6. 6.
    Hughes J, Mellows G (1978) Inhibition of isoleucyl transfer ribonucleic acid synthetase in Escherichia coli by pseudomonic acid. Biochem J 176:305–318PubMedPubMedCentralGoogle Scholar
  7. 7.
    Hughes J, Mellows G (1978) Mode of action of pseudomonic acid—inhibition of protein synthesis in Staphylococcus aureus. J Antibiot 31:330–335PubMedCrossRefGoogle Scholar
  8. 8.
    Hughes J, Mellows G, Soughton S (1980) How does Pseudomonas fluorescens, the producing organism of the antibiotic pseudomonic acid A, avoid suicide. FEBS Lett 122:322–324. doi: 10.1016/0014-5793(80)80465-0 PubMedCrossRefGoogle Scholar
  9. 9.
    Silvian LF, Wang J, Steitz TA (1999) Insights into editing from an Ile-tRNA synthetase structure with tRNA(Ile) and mupirocin. Science 285:1074–1077. doi: 10.1126/science.285.5430.1074 PubMedCrossRefGoogle Scholar
  10. 10.
    Class YJ, DeShong P (1995) The pseudomonic acids. Chem Rev 95:1843–1857. doi: 10.1021/cr00038a005 CrossRefGoogle Scholar
  11. 11.
    Clayton JP, Oliver RS, Rogers NP, King TJ (1979) Chemistry of pseudomonic acid 3. Rearrangement of pseudomonic acid A in acid and basic solution. J Chem Soc Perkin Trans I 838–846. doi: 10.1039/p19790000838
  12. 12.
    Shiozawa H, Kagasaki T, Kinoshita T, Haruyama H, Domon H, Utsui Y, Kodama K, Takahashi S (1993) Thiomarinol, a new hybrid antimicrobial antibiotic produced by a marine bacterium fermentation, isolation, structure, and antimicrobial activity. J Antibiot 46:1834–1842PubMedCrossRefGoogle Scholar
  13. 13.
    Stierle DB, Stierle AA (1992) Pseudomonic acid derivatives from a marine bacterium. Experientia 48:1165–1169. doi: 10.1007/BF01948016 CrossRefGoogle Scholar
  14. 14.
    Shiozawa H, Takahashi S (1994) Configurational studies on thiomarinol. J Antibiot 47:851–853PubMedCrossRefGoogle Scholar
  15. 15.
    Shiozawa H, Kagasaki T, Torikata A, Tanaka N, Fujimoto K, Hata T, Furukawa Y, Takahashi S (1995) Thiomarinol B and thiomarinol C, new antimicrobial antibiotics produced by a marine bacterium. J Antibiot 48:907–909PubMedCrossRefGoogle Scholar
  16. 16.
    Gao X, Hall DG (2005) Catalytic asymmetric synthesis of a potent thiomarinol antibiotic. J Am Chem Soc 127:1628–1629. doi: 10.1021/ja042827p PubMedCrossRefGoogle Scholar
  17. 17.
    Marion O, Gao X, Marcus S, Hall DG (2009) Synthesis and preliminary antibacterial evaluation of simplified thiomarinol analogs. Bioorg Med Chem 17:1006–1017. doi: 10.1016/j.bmc.2008.01.001 PubMedCrossRefGoogle Scholar
  18. 18.
    Breinbauer R, Vetter IR, Waldmann H (2002) From protein domains to drug candidates—natural products as guiding principles in the design and synthesis of compound libraries. Angew Chem Int Ed 41:2878–2890. doi: 10.1002/1521-3773(20020816)41:16<2878:AID-ANIE2878>3.0.CO;2-B
  19. 19.
    Gao X, Hall DG (2003) 3-Boronoacrolein as an exceptional heterodiene in the highly enantio- and diastereoselective Cr(III)-catalyzed three-component [4+2]/allylboration. J Am Chem Soc 125:9308–9309. doi: 10.1021/ja036368o PubMedCrossRefGoogle Scholar
  20. 20.
    Chavez DE, Jacobsen EN (2005) An efficient, highly diastereo- and enantioselective hetero-Diels–Alder catalyst. Preparation of (2S,6R)-6-(tert-butyldimethyl-siloxymethyl)-2-methoxy-2,5-dihydropyran. Org Synth 82:34Google Scholar
  21. 21.
    Gademann K, Chavez DE, Jacobsen EN (2002) Highly enantioselective inverse-electron-demand hetero-Diels–Alder reactions of alpha, beta-unsaturated aldehydes. Angew Chem Int Ed 41:3059–3061. doi: 10.1002/1521-3773(20020816)41:16<3059:AID-ANIE3059>3.0.CO;2-I
  22. 22.
    Evans DA, Andrews GC, Buckwalter B (1974) Metalated allylic ethers as homoenolate anion equivalents. J Am Chem Soc 96:5560–5561. doi: 10.1021/ja00824a039
  23. 23.
    Yamamoto H, Tsuda M, Sakaguchi S, Ishii Y (1997) Selective oxidation of vinyl ethers and silyl enol ethers with hydrogen peroxide catalyzed by peroxotungstophosphate. J Org Chem 62:7174–7177. doi: 10.1021/jo970440h
  24. 24.
    Gao X, Hall DG, Deligny M, Favre A, Carreaux F, Carboni B (2006) Catalytic enantioselective three-component hetero-[4+2] cycloaddition/allylboration approach to alpha-hydroxyalkyl pyrans: scope, limitations, and mechanistic proposal. Chem Eur J 13:3132–3142. doi: 10.1002/chem.200501197 CrossRefGoogle Scholar
  25. 25.
    Li X, Uchiyama T, Raetz CRH, Hindsgaul O (2003) Synthesis of a carbohydrate-derived hydroxamic acid inhibitor of the bacterial enzyme (LpxC) involved in lipid A biosynthesis. Org Lett 5:539–541. doi: 10.1021/ol027458l PubMedCrossRefGoogle Scholar
  26. 26.
    Rolf D, Gray GR (1982) Reductive cleavage of glycosides. J Am Chem Soc 104:3539–3541. doi: 10.1021/ja00376a065
  27. 27.
    Debenham SD, Toone EJ (2000) Regioselective reduction of 4,6-O-benzylidenes using triethylsilane and \(\text{ BF }_{3}\) center dot \(\text{ Et }_{2}\)O. Tetrahedron: Asymmetry 11:385–387. doi:  10.1016/S0957-4166(99)00584-4 CrossRefGoogle Scholar
  28. 28.
    Lipták A, Jodál I, Nánási P (1975) Stereoselective ring-cleavage of 3-O-benzyl-4,6-O-benzylidenehexopyranoside and 2,3-di-O-benzyl-4,6-O-benzylidenehexopyranoside derivatives with \(\text{ LiAlH }_{4}\)\(\text{ AlCl }_{3}\) reagent. Carbohydr Res 44:1–11. doi:  10.1016/S0008-6215(00)84330-X CrossRefGoogle Scholar
  29. 29.
    Garegg PJ, Hultberg H, Wallin S (1982) A novel, reductive ring-opening of carbohydrate benzylidene acetals. Carbohydr Res 108:97–101CrossRefGoogle Scholar
  30. 30.
    Deninno MP, Etienne JB, Duplantier KC (1995) A method for the selective reduction of carbohydrate 4,6-O-benzylidene acetals. Tetrahedron Lett 36:669–672. doi: 10.1016/0040-4039(94)02348-F CrossRefGoogle Scholar
  31. 31.
    Balakumar V, Aravind A, Baskaran S (2004) A highly regio- and chemoselective reductive cleavage of benzylidene acetals with \(\text{ EtAlCl }_{2}\)\(\text{ Et }_{3}\)SiH. Synlett 647–650: doi: 10.1055/s-2004-817752
  32. 32.
    Zhang HX, Xia P, Zhou WS (2003) Novel asymmetric total synthesis of the natural (+)-6-epicastanospermine. Tetrahedron 59:2015–2020. doi: 10.1016/S0040-4020(02)01258-9 CrossRefGoogle Scholar
  33. 33.
    Deligny M, Carreaux F, Carboni B, Toupet L, Dujardin G (2003) A novel diastereoselective route to alpha-hydroxyalkyldihydropyrans using a hetero Diels–Alder/allylboration sequence. Chem Commun 276–277. doi: 10.1039/b208572k
  34. 34.
    Deligny M, Carreaux F, Toupet L, Carboni B (2003) Efficient asymmetric synthesis of 2,6-disubstituted 2H-dihydropyrans via a catalytic hetero-Diels–Alder/allylboration sequence. Adv Synth Catal 345:1215–1219. doi: 10.1002/adsc.200303127 CrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2014

Authors and Affiliations

  1. 1.Department of ChemistryUniversity of AlbertaEdmontonCanada

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