Biomimetic tail-to-head terpene cyclizations using the resorcin[4]arene capsule catalyst.
Journal
Nature protocols
ISSN: 1750-2799
Titre abrégé: Nat Protoc
Pays: England
ID NLM: 101284307
Informations de publication
Date de publication:
01 Dec 2023
01 Dec 2023
Historique:
received:
17
05
2023
accepted:
18
09
2023
medline:
2
12
2023
pubmed:
2
12
2023
entrez:
1
12
2023
Statut:
aheadofprint
Résumé
The tail-to-head terpene (THT) cyclization is a biochemical process that gives rise to many terpene natural product skeletons encountered in nature. Historically, it has been difficult to achieve THT synthetically without using an enzyme. In this protocol, a hexameric resorcin[4]arene capsule acts as an artificial enzyme mimic to carry out biomimetic THT cyclizations and related carbocationic rearrangements. The precursor molecule bears a leaving group (usually an alcohol or acetate group) and undergoes the THT reaction in the presence of the capsule catalyst and HCl as a cocatalyst. Careful control of several parameters (including water content, amount of HCl cocatalyst, temperature and solvent) is crucial to successfully carrying out the reaction. To facilitate the application of this unique capsule-catalysis methodology, we therefore developed a very detailed procedure that includes the preparation and analysis of all reaction components. In this protocol, we describe how to prepare two different terpenes: isolongifolene and presilphiperfolan-1β-ol. The two procedures differ in the water content required for efficient product formation, and thus exemplify the two common use cases of this methodology. The influence of other crucial reaction parameters and means of precisely controlling them are described. A commercially available substrate, nerol, can be used as simple test substrate to validate the reaction setup. Each synthetic procedure requires 5-7 d, including 1-5 h of hands-on time. The protocol applies to the synthesis of many complex terpene natural products that would otherwise be difficult to access in synthetically useful yields.
Identifiants
pubmed: 38040980
doi: 10.1038/s41596-023-00919-3
pii: 10.1038/s41596-023-00919-3
doi:
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2023. Springer Nature Limited.
Références
Christianson, D. W. Structural and chemical biology of terpenoid cyclases. Chem. Rev. 117, 11570–11648 (2017).
pubmed: 28841019
pmcid: 5599884
doi: 10.1021/acs.chemrev.7b00287
Miller, D. J. & Allemann, R. K. Sesquiterpene synthases: passive catalysts or active players? Nat. Prod. Rep. 29, 60–71 (2012).
pubmed: 22068697
doi: 10.1039/C1NP00060H
Pronin, S. V. & Shenvi, R. A. Synthesis of highly strained terpenes by non-stop tail-to-head polycyclization. Nat. Chem. 4, 915–920 (2012).
pubmed: 23089866
doi: 10.1038/nchem.1458
Lesburg, C. A., Zhai, G., Cane, D. E. & Christianson, D. W. Crystal structure of pentalenene synthase: mechanistic insights on terpenoid cyclization reactions in biology. Science 277, 1820 (1997).
pubmed: 9295272
doi: 10.1126/science.277.5333.1820
Starks, C. M., Back, K., Chappell, J. & Noel, J. P. Structural basis for cyclic terpene biosynthesis by tobacco 5-epi-aristolochene synthase. Science 277, 1815 (1997).
pubmed: 9295271
doi: 10.1126/science.277.5333.1815
Guerra-Bubb, J., Croteau, R. & Williams, R. M. The early stages of taxol biosynthesis: an interim report on the synthesis and identification of early pathway metabolites. Nat. Prod. Rep. 29, 683–696 (2012).
pubmed: 22547034
pmcid: 3373433
doi: 10.1039/c2np20021j
Paddon, C. J. et al. High-level semi-synthetic production of the potent antimalarial artemisinin. Nature 496, 528–532 (2013).
pubmed: 23575629
doi: 10.1038/nature12051
Gutsche, C. D., Maycock, J. R. & Chang, C. T. Acid-catalyzed cyclization of farnesol and nerolidol. Tetrahedron 24, 859–876 (1968).
doi: 10.1016/0040-4020(68)88035-4
Ohta, Y. & Hirose, Y. Electrophile-induced cyclization of farnesol. Chem. Lett. 1, 263–266 (1972).
doi: 10.1246/cl.1972.263
Andersen, N. H. & Syrdal, D. D. Chemical simulation of the biogenesis of cedrene. Tetrahedron Lett. 13, 2455–2458 (1972).
doi: 10.1016/S0040-4039(01)84845-0
Kobayashi, S., Tsutsui, M. & Mukaiyama, T. Biogenetic-like cyclization of farnesol and nerolidol to bisabolene by the use of 2-fluorobenzothiazolium salt. Chem. Lett. 6, 1169–1172 (1977).
doi: 10.1246/cl.1977.1169
Croteau, R. Biosynthesis and catabolism of monoterpenoids. Chem. Rev. 87, 929–954 (1987).
doi: 10.1021/cr00081a004
Polovinka, M. P. et al. Cyclization and rearrangements of farnesol and nerolidol stereoisomers in superacids. J. Org. Chem. 59, 1509–1517 (1994).
doi: 10.1021/jo00085a044
Zhang, Q. & Tiefenbacher, K. Terpene cyclization catalysed inside a self-assembled cavity. Nat. Chem. 7, 197–202 (2015).
pubmed: 25698327
doi: 10.1038/nchem.2181
Zhang, Q., Catti, L., Pleiss, J. & Tiefenbacher, K. Terpene cyclizations inside a supramolecular catalyst: leaving-group-controlled product selectivity and mechanistic studies. J. Am. Chem. Soc. 139, 11482–11492 (2017).
pubmed: 28590723
doi: 10.1021/jacs.7b04480
Zhang, Q., Rinkel, J., Goldfuss, B., Dickschat, J. S. & Tiefenbacher, K. Sesquiterpene cyclizations catalysed inside the resorcinarene capsule and application in the short synthesis of isolongifolene and isolongifolenone. Nat. Catal. 1, 609–615 (2018).
pubmed: 30221250
pmcid: 6130823
doi: 10.1038/s41929-018-0115-4
Zhang, Q. & Tiefenbacher, K. Sesquiterpene cyclizations inside the hexameric resorcinarene capsule: total synthesis of δ-selinene and mechanistic studies. Angew. Chem. Int. Ed. 58, 12688–12695 (2019).
doi: 10.1002/anie.201906753
Syntrivanis, L.-D. et al. Four-step access to the sesquiterpene natural product presilphiperfolan-1β-ol and unnatural derivatives via supramolecular catalysis. J. Am. Chem. Soc. 142, 5894–5900 (2020).
pubmed: 32134641
doi: 10.1021/jacs.0c01464
Némethová, I., Schmid, D. & Tiefenbacher, K. Supramolecular capsule catalysis enables the exploration of terpenoid chemical space untapped by nature. Angew. Chem. Int. Ed. 62, e202218625 (2023).
doi: 10.1002/anie.202218625
Kirby, A. J. Enzyme mechanisms, models, and mimics. Angew. Chem. Int. Ed. 35, 706–724 (1996).
doi: 10.1002/anie.199607061
Breslow, R. & Dong, S. D. Biomimetic reactions catalyzed by cyclodextrins and their derivatives. Chem. Rev. 98, 1997–2012 (1998).
pubmed: 11848956
doi: 10.1021/cr970011j
Motherwell, W. B., Bingham, M. J. & Six, Y. Recent progress in the design and synthesis of artificial enzymes. Tetrahedron 57, 4663–4686 (2001).
doi: 10.1016/S0040-4020(01)00288-5
Koblenz, T. S., Wassenaar, J. & Reek, J. N. H. Reactivity within a confined self-assembled nanospace. Chem. Soc. Rev. 37, 247–262 (2008).
pubmed: 18197342
doi: 10.1039/B614961H
Yoshizawa, M., Klosterman, J. K. & Fujita, M. Functional molecular flasks: new properties and reactions within discrete, self-assembled hosts. Angew. Chem. Int. Ed. 48, 3418–3438 (2009).
doi: 10.1002/anie.200805340
Wiester, M. J., Ulmann, P. A. & Mirkin, C. A. Enzyme mimics based upon supramolecular coordination chemistry. Angew. Chem. Int. Ed. 50, 114–137 (2011).
doi: 10.1002/anie.201000380
Ajami, D. & Rebek, J. More chemistry in small spaces. Acc. Chem. Res. 46, 990–999 (2013).
pubmed: 22574934
doi: 10.1021/ar300038r
Raynal, M., Ballester, P., Vidal-Ferran, A. & van Leeuwen, P. W. N. M. Supramolecular catalysis. Part 2: artificial enzyme mimics. Chem. Soc. Rev. 43, 1734–1787 (2014).
pubmed: 24365792
doi: 10.1039/C3CS60037H
Brown, C. J., Toste, F. D., Bergman, R. G. & Raymond, K. N. Supramolecular catalysis in metal–ligand cluster hosts. Chem. Rev. 115, 3012–3035 (2015).
pubmed: 25898212
doi: 10.1021/cr4001226
Leenders, S. H. A. M., Gramage-Doria, R., de Bruin, B. & Reek, J. N. H. Transition metal catalysis in confined spaces. Chem. Soc. Rev. 44, 433–448 (2015).
pubmed: 25340992
doi: 10.1039/C4CS00192C
Zarra, S., Wood, D. M., Roberts, D. A. & Nitschke, J. R. Molecular containers in complex chemical systems. Chem. Soc. Rev. 44, 419–432 (2015).
pubmed: 25029235
doi: 10.1039/C4CS00165F
Borsato, G. & Scarso, A. in Organic Nanoreactors (ed Samahe Sadjadi) 203–234 (Academic Press, 2016).
Zhang, Q., Catti, L. & Tiefenbacher, K. Catalysis inside the hexameric resorcinarene capsule. Acc. Chem. Res. 51, 2107–2114 (2018).
pubmed: 30153000
doi: 10.1021/acs.accounts.8b00320
Mouarrawis, V., Plessius, R., van der Vlugt, J. I. & Reek, J. N. H. Confinement effects in catalysis using well-defined materials and cages. Front. Chem. 6, 623 (2018).
pubmed: 30622940
pmcid: 6308152
doi: 10.3389/fchem.2018.00623
Ward, M. D., Hunter, C. A. & Williams, N. H. Coordination cages based on bis(pyrazolylpyridine) ligands: structures, dynamic behavior, guest binding, and catalysis. Acc. Chem. Res. 51, 2073–2082 (2018).
pubmed: 30085644
doi: 10.1021/acs.accounts.8b00261
Hong, C. M., Bergman, R. G., Raymond, K. N. & Toste, F. D. Self-assembled tetrahedral hosts as supramolecular catalysts. Acc. Chem. Res. 51, 2447–2455 (2018).
pubmed: 30272943
doi: 10.1021/acs.accounts.8b00328
Jongkind, L. J., Caumes, X., Hartendorp, A. P. T. & Reek, J. N. H. Ligand template strategies for catalyst encapsulation. Acc. Chem. Res. 51, 2115–2128 (2018).
pubmed: 30137959
pmcid: 6148444
doi: 10.1021/acs.accounts.8b00345
Fang, Y. et al. Catalytic reactions within the cavity of coordination cages. Chem. Soc. Rev. 48, 4707–4730 (2019).
pubmed: 31339148
doi: 10.1039/C9CS00091G
Gaeta, C. et al. The hexameric resorcinarene capsule at work: supramolecular catalysis in confined spaces. Chem. Eur. J. 25, 4899–4913 (2019).
pubmed: 30499615
doi: 10.1002/chem.201805206
Percástegui, E. G., Ronson, T. K. & Nitschke, J. R. Design and applications of water-soluble coordination cages. Chem. Rev. 120, 13480–13544 (2020).
pubmed: 33238092
pmcid: 7760102
doi: 10.1021/acs.chemrev.0c00672
Némethová, I., Syntrivanis, L.-D. & Tiefenbacher, K. Molecular capsule catalysis: ready to address current challenges in synthetic organic chemistry? Chim. (Aarau) 74, 561–568 (2020).
doi: 10.2533/chimia.2020.561
Morimoto, M. et al. Advances in supramolecular host-mediated reactivity. Nat. Catal. 3, 969–984 (2020).
doi: 10.1038/s41929-020-00528-3
Wang, K., Jordan, J. H., Hu, X.-Y. & Wang, L. Supramolecular strategies for controlling reactivity within confined nanospaces. Angew. Chem. Int. Ed. 59, 13712–13721 (2020).
doi: 10.1002/anie.202000045
Grommet, A. B., Feller, M. & Klajn, R. Chemical reactivity under nanoconfinement. Nat. Nanotechnol. 15, 256–271 (2020).
pubmed: 32303705
doi: 10.1038/s41565-020-0652-2
Hooley, R. J. No, not that way, the other way: creating active sites in self-assembled host molecules. Synlett 31, 1448–1463 (2020).
doi: 10.1055/s-0040-1707125
Mitschke, B., Turberg, M. & List, B. Confinement as a unifying element in selective catalysis. Chem 6, 2515–2532 (2020).
doi: 10.1016/j.chempr.2020.09.007
Yu, Y., Yang, J.-M. & Rebek, J. Molecules in confined spaces: reactivities and possibilities in cavitands. Chem 6, 1265–1274 (2020).
doi: 10.1016/j.chempr.2020.04.014
Ashbaugh, H. S., Gibb, B. C. & Suating, P. Cavitand complexes in aqueous solution: collaborative experimental and computational studies of the wetting, assembly, and function of nanoscopic bowls in water. J. Phys. Chem. B 125, 3253–3268 (2021).
pubmed: 33651614
pmcid: 8040017
doi: 10.1021/acs.jpcb.0c11017
Takezawa, H. & Fujita, M. Molecular confinement effects by self-assembled coordination cages. Bull. Chem. Soc. Jpn 94, 2351–2369 (2021).
doi: 10.1246/bcsj.20210273
Gaeta, C. et al. Supramolecular catalysis with self-assembled capsules and cages: what happens in confined spaces. ChemCatChem 13, 1638–1658 (2021).
doi: 10.1002/cctc.202001570
MacGillivray, L. R. & Atwood, J. L. A chiral spherical molecular assembly held together by 60 hydrogen bonds. Nature 389, 469–472 (1997).
doi: 10.1038/38985
Avram, L. & Cohen, Y. Spontaneous formation of hexameric resorcinarene capsule in chloroform solution as detected by diffusion NMR. J. Am. Chem. Soc. 124, 15148–15149 (2002).
pubmed: 12487570
doi: 10.1021/ja0272686
Avram, L., Cohen, Y. & Rebek, J. Jr Recent advances in hydrogen-bonded hexameric encapsulation complexes. Chem. Commun. 47, 5368–5375 (2011).
doi: 10.1039/C1CC10150A
Yamanaka, M., Shivanyuk, A. & Rebek, J. Kinetics and thermodynamics of hexameric capsule formation. J. Am. Chem. Soc. 126, 2939–2943 (2004).
pubmed: 14995211
doi: 10.1021/ja037035u
Pahima, E., Zhang, Q., Tiefenbacher, K. & Major, D. T. Discovering monoterpene catalysis inside nanocapsules with multiscale modeling and experiments. J. Am. Chem. Soc. 141, 6234–6246 (2019).
pubmed: 30907083
doi: 10.1021/jacs.8b13411
Merget, S., Catti, L., Piccini, G. & Tiefenbacher, K. Requirements for terpene cyclizations inside the supramolecular resorcinarene capsule: bound water and its protonation determine the catalytic activity. J. Am. Chem. Soc. 142, 4400–4410 (2020).
pubmed: 32031794
doi: 10.1021/jacs.9b13239
Sokolova, D., Piccini, G. & Tiefenbacher, K. Enantioselective tail-to-head terpene cyclizations by optically active hexameric resorcin[4]arene capsule derivatives. Angew. Chem. Int. Ed. 61, e202203384 (2022).
doi: 10.1002/anie.202203384
Sobti, R. R. & Dev, S. Synthesis of (±)-isolongifolene. Tetrahedron Lett. 8, 2893–2895 (1967).
doi: 10.1016/S0040-4039(00)90882-7
Sobti, R. R. & Dev, S. Studies in sesquiterpenes—XLIII: isolongifolene (part 4): synthesis. Tetrahedron 26, 649–655 (1970).
doi: 10.1016/S0040-4020(01)97858-5
Hong, A. Y. & Stoltz, B. M. Enantioselective total synthesis of the reported structures of (-)-9-epi-presilphiperfolan-1-ol and (-)-presilphiperfolan-1-ol: structural confirmation and reassignment and biosynthetic insights. Angew. Chem. Int. Ed. 51, 9674–9678 (2012).
doi: 10.1002/anie.201205276
Catti, L. & Tiefenbacher, K. Intramolecular hydroalkoxylation catalyzed inside a self-assembled cavity of an enzyme-like host structure. Chem. Commun. 51, 892–894 (2015).
doi: 10.1039/C4CC08211G
Köster, J. M. & Tiefenbacher, K. Elucidating the importance of hydrochloric acid as a cocatalyst for resorcinarene-capsule-catalyzed reactions. ChemCatChem 10, 2941–2944 (2018).
doi: 10.1002/cctc.201800326