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Mirror-image cyclodextrins

Nature Synthesis volume 3, pages 698–706 (2024) Cite this article

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Abstract

For over a century, naturally occurring cyclodextrins (CDs) have been investigated intensively and extensively. CDs possess inherently stable chiralities, which render them versatile players in diverse arenas of technology. Although naturally occurring CDs can be mass-produced by the enzymatic modification of amylose, their mirror-images have, however, remained inaccessible. Here we report the syntheses of three mirror-image CDs—namely, α-, β- and γ-l-CDs, which are composed of six, seven and eight α-1,4-linked l-glucopyranosyl residues, respectively. Hallmarks of their syntheses include the highly diastereoselective installations of multiple contiguous 1,2-cis l-glucopyranosidic linkages, the rapid assembly of linear oligosaccharides employing one-pot glycosylation strategies and three efficient diastereoselective cyclizations. The structures and inherent chiralities of all three synthetic l-CDs have been established unambiguously by single-crystal X-ray diffraction and induced electronic circular dichroism spectroscopy. The availability of l-CDs has enabled the elucidation of an unprecedented chiral self-sorting of a racemic modification of β-CDs in the solid state and an investigation of the chiral recognition of enantiomeric fenchone by α-l-CD. This research identifies a missing piece of the cyclodextrin jigsaw and sets the stage for scientists to explore the mirror-image world of naturally occurring CDs.

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Fig. 1: Synthesis of α-l-CD.
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Fig. 2: Syntheses of β- and γ-l-CDs.
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Fig. 3: Single-crystal X-ray crystallography.
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Fig. 4: Single-crystal X-ray diffraction analysis of the β-d- and β-l-CD cocrystal.
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Fig. 5: IECD spectroscopy.
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Fig. 6: Chiral recognition.
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Data availability

All data that support the findings of this study are available in the main text and the Supplementary Information. X-Ray crystallographic data for the structures reported in this Article have been deposited at the Cambridge Crystallographic Data Centre (CCDC) under deposition numbers CCDC 2246203 (α-l-CD), 2246204 (β-l-CD), 2246205 (γ-l-CD) and 2266813 (β-d- and β-l-CD cocrystal). Copies of the data can be obtained free of charge via https://www.ccdc.cam.ac.uk/structures/. Source data are provided with this paper.

References

  1. Villiers, A. Sur la fermentation de la fécule par l’action du ferment butyrique. C. R. Hebd. Acad. Sci. Paris 112, 536–538 (1891).

    Google Scholar 

  2. Szejtli, J. Introduction and general overview of cyclodextrin chemistry. Chem. Rev. 98, 1743–1753 (1998).

    Article  CAS  PubMed  Google Scholar 

  3. Crini, G. A history of cyclodextrins. Chem. Rev. 114, 10940–10975 (2014).

    Article  CAS  PubMed  Google Scholar 

  4. Rekharsky, M. V. & Inoue, Y. Complexation thermodynamics of cyclodextrins. Chem. Rev. 98, 1875–1918 (1998).

    Article  CAS  PubMed  Google Scholar 

  5. Liu, Z., Nalluri, S. K. M. & Stoddart, J. F. Surveying macrocyclic chemistry: from flexible crown ethers to rigid cyclophanes. Chem. Soc. Rev. 46, 2459–2478 (2017).

    Article  CAS  PubMed  Google Scholar 

  6. Cram, D. J. The design of molecular hosts, guests, and their complexes (Nobel lecture). Angew. Chem. Int. Ed. Engl. 27, 1009–1020 (1988).

    Article  Google Scholar 

  7. Lehn, J. -M. Supramolecular chemistry—scope and perspectives molecules, supermolecules, and molecular devices (Nobel lecture). Angew. Chem. Int. Ed. Engl. 27, 89–112 (1988).

    Article  Google Scholar 

  8. Chen, Y. & Liu, Y. Cyclodextrin-based bioactive supramolecular assemblies. Chem. Soc. Rev. 39, 495–505 (2010).

    Article  CAS  PubMed  Google Scholar 

  9. Chen, G. & Jiang, M. Cyclodextrin-based inclusion complexation bridging supramolecular chemistry and macromolecular self-assembly. Chem. Soc. Rev. 40, 2254–2266 (2011).

    Article  CAS  PubMed  Google Scholar 

  10. Davis, M. E. & Brewster, M. E. Cyclodextrin-based pharmaceutics: past, present and future. Nat. Rev. Drug Discov. 3, 1023–1035 (2004).

    Article  CAS  PubMed  Google Scholar 

  11. Nepogodiev, S. A. & Stoddart, J. F. Cyclodextrin-based catenanes and rotaxanes. Chem. Rev. 98, 1959–1976 (1998).

    Article  CAS  PubMed  Google Scholar 

  12. Harada, A., Takashima, Y. & Yamaguchi, H. Cyclodextrin-based supramolecular polymers. Chem. Soc. Rev. 38, 875–882 (2009).

    Article  CAS  PubMed  Google Scholar 

  13. Harada, A. Cyclodextrin-based molecular machines. Acc. Chem. Res. 34, 456–464 (2001).

    Article  CAS  PubMed  Google Scholar 

  14. Saenger, W. et al. Structures of the common cyclodextrins and their larger analogues beyond the doughnut. Chem. Rev. 98, 1787–1802 (1998).

    Article  CAS  PubMed  Google Scholar 

  15. Easton, C. J. & Lincoln, S. F. Chiral discrimination by modified cyclodextrins. Chem. Soc. Rev. 25, 163–170 (1996).

    Article  CAS  Google Scholar 

  16. Tang, W. & Ng, S.-C. Facile synthesis of mono-6-amino-6-deoxy-α-, β-, γ-cyclodextrin hydrochlorides for molecular recognition, chiral separation and drug delivery. Nat. Protoc. 3, 691–697 (2008).

    Article  CAS  PubMed  Google Scholar 

  17. Chen, L., Chen, Y., Zhang, Y. & Liu, Y. Photo‐controllable catalysis and chiral monosaccharide recognition induced by cyclodextrin derivatives. Angew. Chem. Int. Ed. 60, 7654–7658 (2021).

    Article  CAS  Google Scholar 

  18. Armstrong, D. W., Ward, T. J., Armstrong, R. D. & Beesley, T. E. Separation of drug stereoisomers by the formation of β-cyclodextrin inclusion complexes. Science 232, 1132–1135 (1986).

    Article  CAS  PubMed  Google Scholar 

  19. Armstrong, D. W., Li, W. & Pitha, J. Reversing enantioselectivity in capillary gas chromatography with polar and nonpolar cyclodextrin derivative phases. Anal. Chem. 62, 214–217 (1990).

    Article  CAS  PubMed  Google Scholar 

  20. Tang, W. & Ng, S.-C. Synthesis of cationic single-isomer cyclodextrins for the chiral separation of amino acids and anionic pharmaceuticals. Nat. Protoc. 2, 3195–3200 (2007).

    Article  CAS  PubMed  Google Scholar 

  21. Breslow, R. & Dong, S. D. Biomimetic reactions catalyzed by cyclodextrins and their derivatives. Chem. Rev. 98, 1997–2012 (1998).

    Article  CAS  PubMed  Google Scholar 

  22. Takahashi, K. Organic reactions mediated by cyclodextrins. Chem. Rev. 98, 2013–2034 (1998).

    Article  CAS  PubMed  Google Scholar 

  23. Guitet, M. et al. NHC‐capped cyclodextrins (ICyDs): insulated metal complexes, commutable multicoordination sphere, and cavity‐dependent catalysis. Angew. Chem. Int. Ed. 52, 7213–7218 (2013).

    Article  CAS  Google Scholar 

  24. Xu, G. et al. Capturing the monomeric (L)CuH in NHC-capped cyclodextrin: cavity-controlled chemoselective hydrosilylation of α,β-unsaturated ketones. Angew. Chem. Int. Ed. 59, 7591–7597 (2020).

    Article  CAS  Google Scholar 

  25. Tugny, C. et al. β-Cyclodextrin–NHC–gold (I) complex (β-ICyD) AuCl: a chiral nanoreactor for enantioselective and substrate-selective alkoxycyclization reactions. ACS Catal. 10, 5964–5972 (2020).

    Article  CAS  Google Scholar 

  26. Huang, J., Zhang, X. & Armstrong, D. W. Highly efficient asymmetric direct stoichiometric aldol reactions on/in water. Angew. Chem. Int. Ed. 46, 9073–9077 (2007).

    Article  CAS  Google Scholar 

  27. Ke, C. et al. Catalytic enantiodifferentiating photocyclodimerization of 2‐anthracenecarboxylic acid mediated by a non‐sensitizing chiral metallosupramolecular host. Angew. Chem. Int. Ed. 48, 6675–6677 (2009).

    Article  CAS  Google Scholar 

  28. Wei, X. et al. Supramolecular photochirogenesis driven by higher-order complexation: enantiodifferentiating photocyclodimerization of 2-anthracenecarboxylate to slipped cyclodimers via a 2:2 complex with β-cyclodextrin. J. Am. Chem. Soc. 140, 3959–3974 (2018).

    Article  CAS  PubMed  Google Scholar 

  29. Ji, J. et al. An ultimate stereocontrol in supramolecular photochirogenesis: photocyclodimerization of 2-anthracenecarboxylate mediated by sulfur-linked β-cyclodextrin dimers. J. Am. Chem. Soc. 141, 9225–9238 (2019).

    Article  CAS  PubMed  Google Scholar 

  30. Wei, X. et al. Synthesis of cyclodextrin derivatives for enantiodifferentiating photocyclodimerization of 2-anthracenecarboxylate. Nat. Protoc. 17, 2494–2516 (2022).

    Article  CAS  PubMed  Google Scholar 

  31. Chen, X.-Y. et al. Selective photodimerization in a cyclodextrin metal–organic framework. J. Am. Chem. Soc. 143, 9129–9139 (2021).

    Article  CAS  PubMed  Google Scholar 

  32. Chen, A. X.-Y. et al. Site-selective C–H functionalization in a cyclodextrin metal–organic framework. Chem 10, 234–249 (2024).

    Article  CAS  Google Scholar 

  33. Smaldone, R. A. et al. Metal–organic frameworks from edible natural products. Angew. Chem. Int. Ed. 49, 8630–8634 (2010).

    Article  CAS  Google Scholar 

  34. Roy, I. & Stoddart, J. F. Cyclodextrin metal–organic frameworks and their applications. Acc. Chem. Res. 54, 1440–1453 (2021).

    Article  CAS  PubMed  Google Scholar 

  35. Shigemitsu, H. et al. Cyclodextrins with multiple pyrenyl groups: an approach to organic molecules exhibiting bright excimer circularly polarized luminescence. Angew. Chem. Int. Ed. 61, e202114700 (2022).

    Article  CAS  Google Scholar 

  36. Tu, C. et al. Host–guest complexation‐induced aggregation based on pyrene‐modified cyclodextrins for improved electronic circular dichroism and circularly polarized luminescence. Angew. Chem. Int. Ed. 61, e202203541 (2022).

    Article  CAS  Google Scholar 

  37. Song, X., Zhu, X., Qiu, S., Tian, W. & Liu, M. Self‐assembly of adaptive chiral [1]rotaxane for thermo‐rulable circularly polarized luminescence. Angew. Chem. Int. Ed. 61, e202208574 (2022).

    Article  CAS  Google Scholar 

  38. Hu, L., Zhu, X., Yang, C. & Liu, M. Two‐dimensional chiral polyrotaxane monolayer with emergent and steerable circularly polarized luminescence. Angew. Chem. Int. Ed. 61, e202114759 (2022).

    Article  CAS  Google Scholar 

  39. Yang, S. et al. Dynamic enzymatic synthesis of γ-cyclodextrin using a photoremovable hydrazone template. Chem 7, 2190–2200 (2021).

    Article  CAS  Google Scholar 

  40. Erichsen, A., Peters, G. H. J. & Beeren, S. R. Templated enzymatic synthesis of δ-cyclodextrin. J. Am. Chem. Soc. 145, 4882–4891 (2023).

    Article  CAS  PubMed  Google Scholar 

  41. Ogawa, T. & Takahashi, Y. Total synthesis of α-cyclodextrin. Carbohydr. Res. 138, C5–C9 (1985).

    Article  CAS  Google Scholar 

  42. Takahashi, Y. & Ogawa, T. Total synthesis of cyclomaltooctaose and an isomer of cyclomaltohexaose, cyclo{→6)-[α-D-Glcp-(1→4)]5-α-D-Glcp-(1-}.Carbohydr. Res. 169, 127–149 (1987).

    Article  CAS  Google Scholar 

  43. Nicolaou, K. C., Vourloumis, D., Winssinger, N. & Baran, P. S. The art and science of total synthesis at the dawn of the twenty‐first century. Angew. Chem. Int. Ed. 39, 44–122 (2000).

    Article  CAS  Google Scholar 

  44. Stoddart, J. F. Unnatural product synthesis. Nature 334, 10–11 (1988).

    Article  Google Scholar 

  45. Ikuta, D. et al. Conformationally supple glucose monomers enable synthesis of the smallest cyclodextrins. Science 364, 674–677 (2019).

    Article  CAS  PubMed  Google Scholar 

  46. Stoddart, J. F. From carbohydrates to enzyme analogues. Chem. Soc. Rev. 8, 85–142 (1979).

    Article  CAS  Google Scholar 

  47. Gattuso, G., Nepogodiev, S. A. & Stoddart, J. F. Synthetic cyclic oligosaccharides. Chem. Rev. 98, 1919–1958 (1998).

    Article  CAS  PubMed  Google Scholar 

  48. Bodine, K. D., Gin, D. Y. & Gin, M. S. Synthesis of readily modifiable cyclodextrin analogues via cyclodimerization of an alkynyl−azido trisaccharide. J. Am. Chem. Soc. 126, 1638–1639 (2004).

    Article  CAS  PubMed  Google Scholar 

  49. Li, X. et al. Promoter-controlled synthesis and conformational analysis of cyclic mannosides up to a 32-mer. Angew. Chem. Int. Ed. 62, e202307851 (2023).

    Article  CAS  Google Scholar 

  50. Boltje, T. J., Kim, J.-H., Park, J. & Boons, G.-J. Chiral-auxiliary-mediated 1,2-cis-glycosylations for the solid-supported synthesis of a biologically important branched α-glucan. Nat. Chem. 2, 552–557 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Yasomanee, J. P. & Demchenko, A. V. Hydrogen bond mediated aglycone delivery: synthesis of linear and branched α-glucans. Angew. Chem. Int. Ed. 53, 10453–10456 (2014).

    Article  CAS  Google Scholar 

  52. Wang, L., Overkleeft, H. S., van der Marel, G. A. & Codée, J. D. C. Reagent controlled stereoselective synthesis of α-glucans. J. Am. Chem. Soc. 140, 4632–4638 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Zhang, Y. et al. A new method for α-specific glucosylation and its application to the one-pot synthesis of a branched α-glucan. Org. Chem. Front. 6, 762–772 (2019).

    Article  CAS  Google Scholar 

  54. Zhang, Y. et al. Merging reagent modulation and remote anchimeric assistance for glycosylation: highly stereoselective synthesis of α-glycans up to a 30-mer. Angew. Chem. Int. Ed. 60, 12597–12606 (2021).

    Article  CAS  Google Scholar 

  55. Zhu, Y., Delbianco, M. & Seeberger, P. H. Automated assembly of starch and glycogen polysaccharides. J. Am. Chem. Soc. 143, 9758–9768 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Zhang, C. et al. Halogen-bond-assisted radical activation of glycosyl donors enables mild and stereoconvergent 1,2-cis-glycosylation. Nat. Chem. 14, 686–694 (2022).

    Article  CAS  PubMed  Google Scholar 

  57. Hettikankanamalage, A. A., Lassfolk, R., Ekholm, F. S., Leino, R. & Crich, D. Mechanisms of stereodirecting participation and ester migration from near and far in glycosylation and related reactions. Chem. Rev. 120, 7104–7151 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Huang, X., Huang, L., Wang, H. & Ye, X.-S. Iterative one‐pot synthesis of oligosaccharides. Angew. Chem. Int. Ed. 43, 5221–5224 (2004).

    Article  CAS  Google Scholar 

  59. Wu, Y., Xiong, D.-C., Chen, S.-C., Wang, Y.-S. & Ye, X.-S. Total synthesis of mycobacterial arabinogalactan containing 92 monosaccharide units. Nat. Commun. 8, 14851 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Saouane, S. & Fabbiani, F. P. A. Structural elucidation of α-cyclodextrin-succinic acid pseudo dodecahydrate: expanding the packing types of α-cyclodextrin inclusion complexes. Crystals 6, 2 (2016).

    Article  Google Scholar 

  61. Aree, T. & Chaichit, N. Crystal form III of β-cyclodextrin–ethanol inclusion complex: layer-type structure with dimeric motif. Carbohydr. Res. 343, 2285–2291 (2008).

    Article  CAS  PubMed  Google Scholar 

  62. Steiner, T. & Saenger, W. Channel-type crystal packing in the very rare space group P4212 with Z’ = 3/4: crystal structure of the complex γ-cyclodextrin–methanol–n-hydrate. Acta Crystallogr. B 54, 450–455 (1998).

    Article  Google Scholar 

  63. Thordarson, P. Determining association constants from titration experiments in supramolecular chemistry. Chem. Soc. Rev. 40, 1305–1323 (2011).

    Article  CAS  PubMed  Google Scholar 

  64. Nowakowski, M. & Ejchart, A. Complex formation of fenchone with α-cyclodextrin: NMR titrations. J. Incl. Phenom. Macrocycl. Chem. 79, 337–342 (2014).

    Article  CAS  PubMed  Google Scholar 

  65. Vidal, S. (ed) Protecting Groups: Strategies and Applications in Carbohydrate Chemistry (Wiley, 2019).

  66. Khan, A. R., Forgo, P., Stine, K. J. & D’Souza, V. T. Methods for selective modifications of cyclodextrins. Chem. Rev. 98, 1977–1996 (1998).

    Article  CAS  PubMed  Google Scholar 

  67. Liu, J. et al. Programmed synthesis of hepta‐differentiated β‐cyclodextrin: 1 out of 117,655 arrangements. Angew. Chem. Int. Ed. 60, 12090–12096 (2021).

    Article  CAS  Google Scholar 

  68. Chen, J., Chen, M. & Zhu, T. F. Directed evolution and selection of biostable l-DNA aptamers with a mirror-image DNA polymerase. Nat. Biotechnol. 40, 1601–1609 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Hahm, H. S. et al. Automated glycan assembly using the Glyconeer 2.1 synthesizer. Proc. Natl Acad. Sci. USA 114, E3385–E3389 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Yao, W. et al. Automated solution-phase multiplicative synthesis of complex glycans up to a 1,080-mer. Nat. Synth. 1, 854–863 (2022).

    Article  Google Scholar 

  71. Cheng, H. & Wang, P. G. Machine assembly of carbohydrates with more than 1,000 sugar units. Nature 610, 266–267 (2022).

    Article  CAS  PubMed  Google Scholar 

  72. Shishiuchi, R. et al. Discovery of α-l-glucosidase raises the possibility of α-l-glucosides in nature. ACS Omega 7, 47411–47423 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

Northwestern University (NU, J.F.S.), the University of Hong Kong (J.F.S.) and the Robert A. Welch Foundation (Y-0026 to D.W.A.) are acknowledged for financial support. This work made use of the Integrated Molecular Structure Education and Research Center (IMSERC) at NU, which receives support from the NIH (1S10OD012016-01/1S10RR019071-01A1), Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource (NSF ECCS-1542205), the State of Illinois and the International Institute for Nanotechnology (IIN). Use of resources of the Keck Biophysics Facility was supported in part by National Cancer Institute award CCSG-P30-CA060553 to the Robert H. Lurie Comprehensive Cancer Center at NU.

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Authors and Affiliations

  1. Department of Chemistry, Northwestern University, Evanston, IL, USA

    Yong Wu, Han Han, Chun Tang, Guangcheng Wu, Xuesong Li, Huang Wu, Charlotte L. Stern, Yunyan Qiu, Aspen X.-Y. Chen, Yang Jiao, Ruihua Zhang, Arthur H. G. David & J. Fraser Stoddart

  2. Department of Chemistry, The University of Hong Kong, Hong Kong SAR, China

    Yong Wu, Han Han, Chun Tang, Guangcheng Wu, Huang Wu, Aspen X.-Y. Chen, Ruihua Zhang & J. Fraser Stoddart

  3. Department of Chemistry and Biochemistry, University of Texas at Arlington, Arlington, TX, USA

    Saba Aslani & Daniel W. Armstrong

  4. Department of Chemistry, University of Wyoming, Laramie, WY, USA

    Xuesong Li

  5. Stoddart Institute of Molecular Science, Department of Chemistry, Zhejiang University, Hangzhou, China

    Qing-Hui Guo & J. Fraser Stoddart

  6. ZJU-Hangzhou Global Scientific and Technological Innovation Center, Hangzhou, China

    Qing-Hui Guo & J. Fraser Stoddart

  7. Department of Chemistry, National University of Singapore, Singapore, Republic of Singapore

    Yunyan Qiu

  8. Laboratoire MOLTECH-Anjou, UMR CNRS 6200, Université d’Angers, Angers, France

    Arthur H. G. David

  9. Simpson Querrey Institute for BioNanotechnology, Northwestern University, Chicago, IL, USA

    J. Fraser Stoddart

  10. School of Chemistry, University of New South Wales, Sydney, New South Wales, Australia

    J. Fraser Stoddart

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  1. Yong Wu
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Contributions

Y.W. and J.F.S. conceived the study and designed experiments. Y.W. performed research under J.F.S.’s guidance. S.A., G.W. and D.W.A. contributed to the chiral recognition experiments. H.H. conducted density functional theory calculations. C.T. contributed to the IECD spectroscopy and X-ray crystallographic analysis. C.L.S. collected and solved the X-ray diffraction data. X.L., H.W., Q.-H.G., Y.Q., A.X.-Y.C., Y.J., R.Z. and A.H.G.D. commented on the data and all authors contributed to data analysis. Y.W. and J.F.S. wrote the manuscript with input from all authors.

Corresponding author

Correspondence to J. Fraser Stoddart.

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Competing interests

Y.W. and J.F.S. have filed a patent application with Northwestern University (Innovation and New Ventures Office Reference No. NU 2024-020) based on this research. The other authors declare no competing interests.

Peer review

Peer review information

Nature Synthesis thanks Sophie Beeren, William Harrison, Chang-Chun Ling and Peng George Wang for their contribution to the peer review of this work. Primary handling editor: Peter Seavill.

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Publisher’s note The editorial team of Nature Synthesis declare that Alison Stoddart has had no involvement in the editorial handling of this article.

Supplementary information

Supplementary Information (download PDF )

Experimental Details, Supplementary Figs. 1–48 and Schemes 1–17.

Supplementary Data 1

X-ray crystallographic data for α-l-CD, CCDC 2246203.

Supplementary Data 2

X-ray crystallographic data for β-l-CD, CCDC 2246204.

Supplementary Data 3

X-ray crystallographic data for γ-l-CD, CCDC 2246205.

Supplementary Data 4

X-ray crystallographic data for β-d- and β-l-CD cocrystal, CCDC 2266813.

Source data

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Wu, Y., Aslani, S., Han, H. et al. Mirror-image cyclodextrins. Nat. Synth 3, 698–706 (2024). https://doi.org/10.1038/s44160-024-00495-8

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