Atropselective syntheses of (−) and (+) rugulotrosin A utilizing point-to-axial chirality transfer

Journal name:
Nature Chemistry
Year published:
Published online


Chiral, dimeric natural products containing complex structures and interesting biological properties have inspired chemists and biologists for decades. A seven-step total synthesis of the axially chiral, dimeric tetrahydroxanthone natural product ​rugulotrosin A is described. The synthesis employs a one-pot Suzuki coupling/dimerization to generate the requisite 2,2′-biaryl linkage. Highly selective point-to-axial chirality transfer was achieved using palladium catalysis with achiral phosphine ligands. Single X-ray crystal diffraction data were obtained to confirm both the atropisomeric configuration and absolute stereochemistry of ​rugulotrosin A. Computational studies are described to rationalize the atropselectivity observed in the key dimerization step. Comparison of the crude fungal extract with synthetic ​rugulotrosin A and its atropisomer verified that nature generates a single atropisomer of the natural product.

At a glance


  1. Axially chiral, dimeric tetrahydroxanthone natural products and point-to-axial chirality transfer strategy.
    Figure 1: Axially chiral, dimeric tetrahydroxanthone natural products and point-to-axial chirality transfer strategy.

    a, Structures of the dimeric tetrahydroxanthone natural products secalonic acids B and D. b, Structures of representative axially chiral tetrahydroxanthone natural products. c, Select literature examples of remote point-to-axial chirality transfer. d, Strategy for the synthesis of ​rugulotrosin A.

  2. Scalable syntheses of enantiopure tetrahydroxanthone monomers.
    Figure 2: Scalable syntheses of enantiopure tetrahydroxanthone monomers.

    Key steps involve siloxyfuran addition to a benzopyrylium species (12 to (±)-13) followed by kinetic acylative resolution of (±)-17 using the Birman catalyst.

  3. One-pot Suzuki dimerization of chiral tetrahydroxanthone monomers (+)-18.
    Figure 3: One-pot Suzuki dimerization of chiral tetrahydroxanthone monomers (+)-18.

    Optimal conditions shown using ​Pd(OAc)2 and ​SPhos as achiral ligand.

  4. Syntheses of (−) and (+)-rugulotrosin A and atrop-rugulotrosin A.
    Figure 4: Syntheses of (−) and (+)-rugulotrosin A and atrop-rugulotrosin A.

    a, Synthesis of ent-rugulotrosin A. b, Synthesis of ​rugulotrosin A and comparison rotation data with natural sample. c, Synthesis of atrop-rugulotrosin A. d, Synthesis of ent-atrop-rugulotrosin A. e, Comparison between the natural extract and synthetic rugulotrosins. HPLC-DAD (210 nm) (Zorbax C18 column, gradient elution H2O/​MeCN plus 0.05% ​HCO2H) analysis of 21-day Penicillium nov. sp. (MST-F8741) cultures extracted with (i) ​MeCN or (ii) ​MeOH, compared against (iii) natural (+)-1, (iv) synthetic (+)-1, (v) (-)-23 and (vi) a mixture of (+)-1, (-)-1, (-)-23 and (+)-23. mAU, milli absorption units.

  5. Computational studies for atropselective Suzuki dimerization.
    Figure 5: Computational studies for atropselective Suzuki dimerization.

    Conformational analysis was optimized at the B3LYP/LanL2DZ level of theory. Dihedral angles were measured by C1, C2, C2′ and C1′ and are shown in green. a, Conformers leading to (-)-19. b, Conformers leading to 20.


37 compounds View all compounds
  1. Rugulotrosin A
    Compound 1 Rugulotrosin A
  2. Rugulotrosin A
    Compound (+)-1 Rugulotrosin A
  3. ent-Rugulotrosin A
    Compound (-)-1 ent-Rugulotrosin A
  4. Rugulotrosin B
    Compound 2 Rugulotrosin B
  5. Gonytolide E
    Compound 3 Gonytolide E
  6. Gonytolide A
    Compound 4 Gonytolide A
  7. (S)-7-Hydroxy-9-isopropoxy-10-methoxy-3-(2-((triisopropylsilyl)oxy)ethyl)-3,4-dihydro-1H-benzo[g]isochromen-1-one
    Compound 5 (S)-7-Hydroxy-9-isopropoxy-10-methoxy-3-(2-((triisopropylsilyl)oxy)ethyl)-3,4-dihydro-1H-benzo[g]isochromen-1-one
  8. (3S,3'S,6R)-7,7'-Dihydroxy-9,9'-diisopropoxy-10,10'-dimethoxy-3,3'-bis(2-((triisopropylsilyl)oxy)ethyl)-3,3',4,4'-tetrahydro-1H,1'H-[6,6'-bibenzo[g]isochromene]-1,1'-dione
    Compound 6 (3S,3'S,6R)-7,7'-Dihydroxy-9,9'-diisopropoxy-10,10'-dimethoxy-3,3'-bis(2-((triisopropylsilyl)oxy)ethyl)-3,3',4,4'-tetrahydro-1H,1'H-[6,6'-bibenzo[g]isochromene]-1,1'-dione
  9. (4-(Benzyloxy)-5-methoxy-7-(((triisopropylsilyl)oxy)methyl)naphthalen-1-yl)boronic acid
    Compound 7 (4-(Benzyloxy)-5-methoxy-7-(((triisopropylsilyl)oxy)methyl)naphthalen-1-yl)boronic acid
  10. ((1R,3S)-6,8-Bis(benzyloxy)-5-iodo-1-methyl-2-tosyl-1,2,3,4-tetrahydroisoquinolin-3-yl)methyl 2-naphthoate
    Compound 8 ((1R,3S)-6,8-Bis(benzyloxy)-5-iodo-1-methyl-2-tosyl-1,2,3,4-tetrahydroisoquinolin-3-yl)methyl 2-naphthoate
  11. ((1R,3S,5R)-6,8-Bis(benzyloxy)-5-(4-(benzyloxy)-5-methoxy-7-(((triisopropylsilyl)oxy)methyl)naphthalen-1-yl)-1-methyl-2-tosyl-1,2,3,4-tetrahydroisoquinolin-3-yl)methyl 2-naphthoate
    Compound 9 ((1R,3S,5R)-6,8-Bis(benzyloxy)-5-(4-(benzyloxy)-5-methoxy-7-(((triisopropylsilyl)oxy)methyl)naphthalen-1-yl)-1-methyl-2-tosyl-1,2,3,4-tetrahydroisoquinolin-3-yl)methyl 2-naphthoate
  12. Methyl 5-hydroxy-7-methyl-4-oxo-4H-chromene-2-carboxylate
    Compound 12 Methyl 5-hydroxy-7-methyl-4-oxo-4H-chromene-2-carboxylate
  13. (±)-Methyl (R)-5-hydroxy-7-methyl-4-oxo-2-((R)-5-oxotetrahydrofuran-2-yl)chromane-2-carboxylate
    Compound (±)-13 (±)-Methyl (R)-5-hydroxy-7-methyl-4-oxo-2-((R)-5-oxotetrahydrofuran-2-yl)chromane-2-carboxylate
  14. (±)-Methyl (4R,4aR)-1,4,8-trihydroxy-6-methyl-9-oxo-2,3,4,9-tetrahydro-4aH-xanthene-4a-carboxylate
    Compound (±)-14 (±)-Methyl (4R,4aR)-1,4,8-trihydroxy-6-methyl-9-oxo-2,3,4,9-tetrahydro-4aH-xanthene-4a-carboxylate
  15. (±)-Methyl (4R,4aR)-4,8-dihydroxy-9-methoxy-6-methyl-1-oxo-1,2,3,4-tetrahydro-4aH-xanthene-4a-carboxylate
    Compound (±)-15 (±)-Methyl (4R,4aR)-4,8-dihydroxy-9-methoxy-6-methyl-1-oxo-1,2,3,4-tetrahydro-4aH-xanthene-4a-carboxylate
  16. (±)-Methyl (4R,4aR)-4,8-dihydroxy-1-methoxy-6-methyl-9-oxo-2,3,4,9-tetrahydro-4aH-xanthene-4a-carboxylate
    Compound (±)-16 (±)-Methyl (4R,4aR)-4,8-dihydroxy-1-methoxy-6-methyl-9-oxo-2,3,4,9-tetrahydro-4aH-xanthene-4a-carboxylate
  17. (±)-Methyl (4R,4aR)-4,8-dihydroxy-7-iodo-1-methoxy-6-methyl-9-oxo-2,3,4,9-tetrahydro-4aH-xanthene-4a-carboxylate
    Compound (±)-17 (±)-Methyl (4R,4aR)-4,8-dihydroxy-7-iodo-1-methoxy-6-methyl-9-oxo-2,3,4,9-tetrahydro-4aH-xanthene-4a-carboxylate
  18. Methyl (4S,4aS)-4,8-dihydroxy-7-iodo-1-methoxy-6-methyl-9-oxo-2,3,4,9-tetrahydro-4aH-xanthene-4a-carboxylate
    Compound (-)-17 Methyl (4S,4aS)-4,8-dihydroxy-7-iodo-1-methoxy-6-methyl-9-oxo-2,3,4,9-tetrahydro-4aH-xanthene-4a-carboxylate
  19. Methyl (4R,4aR)-8-hydroxy-7-iodo-1-methoxy-6-methyl-9-oxo-4-(propionyloxy)-2,3,4,9-tetrahydro-4aH-xanthene-4a-carboxylate
    Compound (+)-18 Methyl (4R,4aR)-8-hydroxy-7-iodo-1-methoxy-6-methyl-9-oxo-4-(propionyloxy)-2,3,4,9-tetrahydro-4aH-xanthene-4a-carboxylate
  20. Dimethyl (2R,5S,5'S,10aS,10'aS)-1,1',5,5'-tetrahydroxy-8,8'-dimethoxy-3,3'-dimethyl-9,9'-dioxo-5,5',6,6',7,7',9,9'-octahydro-10aH,10'aH-[2,2'-bixanthene]-10a,10'a-dicarboxylate
    Compound (-)-19 Dimethyl (2R,5S,5'S,10aS,10'aS)-1,1',5,5'-tetrahydroxy-8,8'-dimethoxy-3,3'-dimethyl-9,9'-dioxo-5,5',6,6',7,7',9,9'-octahydro-10aH,10'aH-[2,2'-bixanthene]-10a,10'a-dicarboxylate
  21. Dimethyl (5S,5'S,10aS,10'aS)-1,1',5,5'-tetrahydroxy-8,8'-dimethoxy-3,3'-dimethyl-9,9'-dioxo-5,5',6,6',7,7',9,9'-octahydro-10aH,10'aH-[2,2'-bixanthene]-10a,10'a-dicarboxylate
    Compound 20 Dimethyl (5S,5'S,10aS,10'aS)-1,1',5,5'-tetrahydroxy-8,8'-dimethoxy-3,3'-dimethyl-9,9'-dioxo-5,5',6,6',7,7',9,9'-octahydro-10aH,10'aH-[2,2'-bixanthene]-10a,10'a-dicarboxylate
  22. Dimethyl (5R,5'R,10aR,10'aR)-1,1'-dihydroxy-8,8'-dimethoxy-3,3'-dimethyl-9,9'-dioxo-5,5'-bis(propionyloxy)-5,5',6,6',7,7',9,9'-octahydro-10aH,10'aH-[2,2'-bixanthene]-10a,10'a-dicarboxylate
    Compound (+)-21 Dimethyl (5R,5'R,10aR,10'aR)-1,1'-dihydroxy-8,8'-dimethoxy-3,3'-dimethyl-9,9'-dioxo-5,5'-bis(propionyloxy)-5,5',6,6',7,7',9,9'-octahydro-10aH,10'aH-[2,2'-bixanthene]-10a,10'a-dicarboxylate
  23. Dimethyl (5S,5'S,10aS,10'aS)-1,1'-dihydroxy-8,8'-dimethoxy-3,3'-dimethyl-9,9'-dioxo-5,5'-bis(propionyloxy)-5,5',6,6',7,7',9,9'-octahydro-10aH,10'aH-[2,2'-bixanthene]-10a,10'a-dicarboxylate
    Compound (+)-22 Dimethyl (5S,5'S,10aS,10'aS)-1,1'-dihydroxy-8,8'-dimethoxy-3,3'-dimethyl-9,9'-dioxo-5,5'-bis(propionyloxy)-5,5',6,6',7,7',9,9'-octahydro-10aH,10'aH-[2,2'-bixanthene]-10a,10'a-dicarboxylate
  24. Dimethyl (2R,5R,5'R,10aR,10'aR)-1,1'-dihydroxy-8,8'-dimethoxy-3,3'-dimethyl-9,9'-dioxo-5,5'-bis(propionyloxy)-5,5',6,6',7,7',9,9'-octahydro-10aH,10'aH-[2,2'-bixanthene]-10a,10'a-dicarboxylate
    Compound (-)-22 Dimethyl (2R,5R,5'R,10aR,10'aR)-1,1'-dihydroxy-8,8'-dimethoxy-3,3'-dimethyl-9,9'-dioxo-5,5'-bis(propionyloxy)-5,5',6,6',7,7',9,9'-octahydro-10aH,10'aH-[2,2'-bixanthene]-10a,10'a-dicarboxylate
  25. ent-atrop-Rugulotrosin A
    Compound (+)-23 ent-atrop-Rugulotrosin A
  26. atrop-Rugulotrosin A
    Compound (-)-23 atrop-Rugulotrosin A
  27. SPhos
    Compound L1 SPhos
  28. XPhos
    Compound L2 XPhos
  29. RuPhos
    Compound L3 RuPhos
  30. Dicyclohexyl(2-(2-methoxynaphthalen-1-yl)phenyl)phosphane
    Compound L4 Dicyclohexyl(2-(2-methoxynaphthalen-1-yl)phenyl)phosphane
  31. BI-DIME
    Compound L5 BI-DIME
  32. S-Cy-MOP
    Compound L6 S-Cy-MOP
  33. R-Cy-MOP
    Compound L7 R-Cy-MOP
  34. R-Cy-iPr-MOP
    Compound L8 R-Cy-iPr-MOP
  35. SPhos-Gen 3 pre-catalyst
    Compound C1 SPhos-Gen 3 pre-catalyst
  36. S-Cy-MOP-Gen 3 pre-catalyst
    Compound C2 S-Cy-MOP-Gen 3 pre-catalyst
  37. R-Cy-MOP-Gen 3 pre-catalyst
    Compound C3 R-Cy-MOP-Gen 3 pre-catalyst


  1. Moss, G. P. Basic terminology of stereochemistry. Pure Appl. Chem. 68, 21932222 (1996).
  2. Zask, A., Murphy, J. & Ellestad, G. A. Biological stereoselectivity of atropisomeric natural products and drugs. Chirality 25, 265274 (2013).
  3. Clayden, J., Moran, W. J., Edwards, P. J. & LaPlante, S. R. The challenge of atropisomerism in drug discovery. Angew. Chem. Int. Ed. 48, 63986401 (2009).
  4. LaPlante, S. R., Edwards, P. J., Fader, L. D., Jakalian, A. & Hucke, O. Revealing atropisomer axial chirality in drug discovery. ChemMedChem 6, 505513 (2011).
  5. Bringmann, G. et al. Atroposelective synthesis of axially chiral biaryl compounds. Angew. Chem. Int. Ed. 44, 53875427 (2005).
  6. Bringmann, G., Gulder, T., Gulder, T. A. M. & Breuning, M. Atroposelective total synthesis of axially chiral biaryl natural products. Chem. Rev. 111, 563639 (2011).
  7. Kozlowski, M. C., Morgan, B. J. & Linton, E. C. Total synthesis of chiral biaryl natural products by asymmetric biaryl coupling. Chem. Soc. Rev. 38, 31933207 (2009).
  8. Liau, B. B., Milgram, B. C. & Shair, M. D. Total syntheses of HMP-Y1, hibarimicinone, and HMP-P1. J. Am. Chem. Soc. 134, 1676516772 (2012).
  9. Masters, K-S. & Bräse, S. Xanthones from fungi, lichens, and bacteria: the natural products and their synthesis. Chem. Rev. 112, 37173776 (2012).
  10. Wezeman, T., Masters, K-S. & Bräse, S. Double trouble—the art of synthesis of chiral dimeric natural products. Angew. Chem. Int. Ed. 53, 45244526 (2014).
  11. Franck, B., Gottschalk, E. M., Ohnsorge, U. & Baumann, G. The structure of secalonic acids A and B. Angew. Chem. Int. Ed. Engl. 3, 441442 (1964).
  12. Steyn, P. S. The isolation, structure and absolute configuration of secalonic acid D, the toxic metabolite of Penicillium oxalicum. Tetrahedron 26, 5157 (1970).
  13. Stewart, M. et al. Rugulotrosins A and B: two new antibacterial metabolites from an Australian isolate of a Penicillium sp. J. Nat. Prod. 67, 728730 (2004).
  14. Kikuchi, H., Isobe, M., Kurata, S., Katou, Y. & Oshima, Y. New dimeric and monomeric chromanones, gonytolides D-G, isolated from the fungus Gonytrichum sp. Tetrahedron 68, 62186223 (2012).
  15. Kikuchi, H. et al. Structures of the dimeric and monomeric chromanones, gonytolides A–C, isolated from the fungus Gonytrichum sp. and their promoting activities of innate immune responses. Org. Lett. 13, 46244627 (2011).
  16. Nicolaou, K. C. & Li, A. Total syntheses and structural revision of α- and β-diversonolic esters and total syntheses of diversonol and blennolide C. Angew. Chem. Int. Ed. 47, 65796582 (2008).
  17. Tietze, L. F. et al. Enantioselective total synthesis of (−)-diversonol. Chem. Eur. J. 19, 48764882 (2013).
  18. Tietze, L. F., Ma, L., Reiner, J. R., Jackenkroll, S. & Heidemann, S. Enantioselective total synthesis of (−)-blennolide A. Chem. Eur. J. 19, 86108614 (2013).
  19. Tietze, L. F., Jackenkroll, S., Hierold, J., Ma, L. & Waldecker, B. A domino approach to the enantioselective total syntheses of blennolide C and gonytolide C. Chem. Eur. J. 20, 86288635 (2014).
  20. Nising, C. F., Ohnemüller, U. K. & Bräse, S. The total synthesis of the fungal metabolite diversonol. Angew. Chem. Int. Ed. 45, 307309 (2006).
  21. Meister, A. C. et al. Total synthesis of blennolide mycotoxins: design, synthetic routes and completion. Eur. J. Org. Chem. 48614875 (2014).
  22. Qin, T., Johnson, R. P. & Porco, J. A. Jr Vinylogous addition of siloxyfurans to benzopyryliums: a concise approach to the tetrahydroxanthone natural products. J. Am. Chem. Soc. 133, 17141717 (2011).
  23. Qin, T. & Porco, J. A. Jr Total syntheses of secalonic acids A and D. Angew. Chem. Int. Ed. 53, 31073110 (2014).
  24. Wilson, J. M. & Cram, D. J. Chiral leaving groups induce asymmetry in syntheses of binaphthyls in nucleophilic aromatic substitution reactions. J. Am. Chem. Soc. 104, 881884 (1982).
  25. Evans, D. A. et al. Nonconventional stereochemical issues in the design of the synthesis of the vancomycin antibiotics: challenges imposed by axial and nonplanar chiral elements in the heptapeptide aglycons. Angew. Chem. Int. Ed. 37, 27042708 (1998).
  26. Burns, N. Z., Krylova, Z. N., Hanroush, R. N. & Baran, P. S. Scalable total synthesis and biological evaluation of haouamine A and its atropisomer. J. Am. Chem. Soc. 131, 91729173 (2009).
  27. Guo, F., Konkol, L. C. & Thomson, R. J. Enantioselective synthesis of biphenols from 1,4-diketones by traceless central-to-axial chirality exchange. J. Am. Chem. Soc. 133, 1820 (2011).
  28. Konkol, L. C., Guo, F., Sarjeant, A. A. & Thomson, R. J. Enantioselective total synthesis and studies into the configurational stability of bismurrayaquinone A. Angew. Chem. Int. Ed. 50, 99319934 (2011).
  29. Park, Y. S. et al. Synthesis of (−)-viriditoxin: a 6,6′-binaphthopyran-2-one that targets the bacterial cell division protein FtsZ. Angew. Chem. Int. Ed. 50, 37303733 (2011).
  30. Lipshutz, B. H. & Keith, L. M. A stereospecific, intermolecular biaryl-coupling approach to korupensamine A en route to the michellamines. Angew. Chem. Int. Ed. 38, 35303533 (1999).
  31. Huang, S., Peterson, T. B. & Lipshutz, B. H. Total synthesis of (+)-korupensamine B via an atropselective intermolecular biaryl coupling. J. Am. Chem. Soc. 132, 1402114023 (2010).
  32. Coleman, R. S. & Grant, E. B. Atropdiastereoselective total synthesis of phleichrome and the protein kinase C inhibitor calphostin A. J. Am. Chem. Soc. 116, 87958796 (1994).
  33. Broka, C. A. Total syntheses of phleichrome, calphostin A, and calphostin D. Unusual stereoselective and stereospecific reactions in the synthesis of perylenequinones. Tetrahedron Lett. 32, 859862 (1991).
  34. Birman, V. B. & Li, X. Homobenzotetramisole: an effective catalyst for kinetic resolution of aryl-cycloalkanols. Org. Lett. 10, 11151118 (2008).
  35. Müller, C. E. & Schreiner, P. R. Organocatalytic enantioselective acyl transfer onto racemic as well as meso alcohols, amines, and thiols. Angew. Chem. Int. Ed. 50, 60126042 (2010).
  36. Barder, T. E., Walker, S. D., Martinelli, J. R. & Buchwald, S. L. Catalysts for Suzuki–Miyaura coupling processes: scope and studies of the effect of ligand structure. J. Am. Chem. Soc. 127, 46854696 (2005).
  37. Masamune, S., Choy, W., Petersen, J. S. & Sita, L. R. Double asymmetric synthesis and a new strategy for stereochemical control in organic synthesis. Angew. Chem. Int. Ed. Engl. 24, 130 (1985).
  38. Tang, W. et al. A general and special catalyst for Suzuki–Miyaura coupling processes. Angew. Chem. Int. Ed. 49, 58795883 (2010).
  39. Xu, G., Fu, W., Liu, G., Senanayake, C. H. & Tang, W. Efficient syntheses of korupensamines A, B and michellamine B by asymmetric Suzuki–Miyaura coupling reactions. J. Am. Chem. Soc. 136, 570573 (2014).
  40. Hamada, T., Chieffi, A., Ahman, J. & Buchwald, S. L. An improved catalyst for the asymmetric arylation of ketone enolates. J. Am. Chem. Soc. 124, 12611268 (2002).
  41. Zhou, Y. et al. Enantioselective synthesis of axially chiral multifunctionalized biaryls via asymmetric Suzuki–Miyaura coupling. Org. Lett. 15, 55085511 (2013).
  42. Zhou, Y. et al. Enantioselective synthesis of axially chiral biaryl monophosphine oxides via direct asymmetric Suzuki coupling and DFT investigations of the enantioselectivity. ACS Catal. 4, 13901397 (2014).
  43. Bruno, N. C., Tudge, M. T. & Buchwald, S. L. Design and preparation of new palladium precatalysts for C–C and C–N cross-coupling reactions. Chem. Sci. 4, 916920 (2013).
  44. Little, S. & Trice, J. in Encyclopedia of Reagents for Organic Synthesis (Wiley, 2001);
  45. Molander, G. A., Trice, S. L. J., Kennedy, S. M., Dreher, S. D. & Tudge, M. T. Scope of the palladium-catalyzed aryl borylation utilizing bis-boronic acid. J. Am. Chem. Soc. 134, 1166711673 (2012).
  46. Gensch, T. et al. Snapshot of the palladium (II)-catalyzed oxidative biaryl bond formation by X-ray analysis of the intermediate diaryl palladium (II) complex. Chem. Eur. J. 18, 770776 (2012).
  47. Shen, X., Jones, G. O., Watson, D. A., Bhayana, B. & Buchwald, S. L. Enantioselective synthesis of axially chiral biaryls by the Pd-catalyzed Suzuki–Miyaura reaction: substrate scope and quantum mechanical investigation. J. Am. Chem. Soc. 132, 1127811287 (2010).
  48. Martin, R. & Buchwald, S. L. Palladium-catalyzed Suzuki–Miyaura cross-coupling reactions employing dialkylbiaryl phosphine ligands. Acc. Chem. Res. 41, 14611473 (2008).

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Author information


  1. Department of Chemistry and Center for Molecular Discovery (BU-CMD), Boston University, Boston, Massachusetts 02215, USA

    • Tian Qin &
    • John A. Porco Jr
  2. Department of Chemistry, University of New Hampshire, Durham, New Hampshire 03824, USA

    • Sarah L. Skraba-Joiner &
    • Richard P. Johnson
  3. The University of Queensland, Institute of Molecular Bioscience, 306 Carmody Road, St Lucia, Queensland 4072, Australia

    • Zeinab G. Khalil &
    • Robert J. Capon


T.Q. and J.A.P. conceived of the project, designed and carried out the experiments, analysed the data and wrote most of the paper. S.L.S-J. and R.P.J. performed computational studies. Z.G.K. and R.J.C. performed natural extract comparisons and biological studies. All authors discussed the results and commented on the manuscript.

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The authors declare no competing financial interests.

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Crystallographic information files

  1. Supplementary information (121 KB)

    Crystallographic data for compound (-)-19.

  2. Supplementary information (248 KB)

    Crystallographic data for compound (-)-22.

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