DOI: 10.1002/ange.201407088. Biomimetic Synthesis of the Calcineurin Phosphatase Inhibitor Dibefurin

Biomimetic Synthesis of the Calcineurin Phosphatase Inhibitor Dibefurin

10.1002/ange.201407088

Crossref journal-article

Wiley

Angewandte Chemie (311)

Abstract

AbstractDibefurin is a Ci‐symmetric natural product that acts as an inhibitor of calcineurin phosphatase. A six‐step synthesis of this compound is reported, which features an oxidative dimerization of the aromatic polyketide epicoccine as the key step. Dibefurin is proposed to be related to epicolactone, a complex yet racemic fungal metabolite that has recently been discovered. Attempts to access epicolactone from epicoccine and epicoccone B resulted in an unusual dimer that is formed through a hetero‐Diels–Alder reaction of a para‐quinone methide with an ortho‐quinone.

Bibliography

Ellerbrock, P., Armanino, N., & Trauner, D. (2014). Biomimetic Synthesis of the Calcineurin Phosphatase Inhibitor Dibefurin. Angewandte Chemie, 126(49), 13632â13636. Portico.

Authors 3

Pascal Ellerbrock (first)
Nicolas Armanino (additional)
Dirk Trauner (additional)

References 88 Referenced 20

For reviews:
10.1002/anie.201402384
10.1002/ange.201402384
10.1002/anie.201006017
10.1002/ange.201006017
10.1039/c1np00028d
10.1016/j.tet.2010.05.078
For selected syntheses involving oxidation of phenolic compounds:
10.1002/(SICI)1521-3773(19991203)38:23<3555::AID-ANIE3555>3.0.CO;2-Z
10.1002/(SICI)1521-3757(19991203)111:23<3762::AID-ANGE3762>3.0.CO;2-V
10.1021/ja9942843
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10.1021/ja021396c
10.1002/anie.201302847
10.1002/ange.201302847
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10.1002/anie.201002264
10.1002/ange.201002264
10.1021/ol061737h
10.1002/anie.200705816
10.1002/ange.200705816
10.1002/anie.200604610
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10.1002/anie.201304624
10.1002/ange.201304624
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10.1039/B711474E
{'key': 'e_1_2_3_20_2', 'first-page': '723', 'volume': '69', 'author': 'Salfeld J.', 'year': '1957', 'journal-title': 'Angew. Chem.'} / Angew. Chem. by Salfeld J. (1957)
10.1002/cber.19610940517
10.1002/anie.198502241
10.1002/ange.19850970317
10.1002/9780470742761
10.1002/anie.200806121
10.1002/ange.200806121
10.1007/978-94-010-9132-9
10.1016/S0007-1536(61)80028-4
10.5650/jos1996.45.1321
10.1055/s-2003-43209
10.1002/ejoc.200800447
10.1002/ejoc.201300146
10.1021/np4005745
10.1002/ejoc.201200757
10.7164/antibiotics.49.124
Dibefurin was isolated from a fungus of phylum Basidiomycota;Epicoccumbelongs to the phylum Ascomycota (personal communication with Dr. George S. Sheppard AbbVie).
OtherCi‐symmetric natural products are truxillic acid derivatives:
{'key': 'e_1_2_3_38_2', 'first-page': '403', 'volume': '59', 'author': 'Krauze‐Baranowska M.', 'year': '2002', 'journal-title': 'Acta Pol. Pharm.'} / Acta Pol. Pharm. by Krauze‐Baranowska M. (2002)
10.2174/1874104500802010026
{'key': 'e_1_2_3_40_2', 'first-page': '390', 'volume': '66', 'author': 'Dhar K. L.', 'year': '1995', 'journal-title': 'Fitoterapia'} / Fitoterapia by Dhar K. L. (1995)
10.1016/0031-9422(81)85125-4
10.1016/S0031-9422(97)00105-2
For isolation of rugulosin:
10.1021/jf60207a028
10.1002/anie.200503678
10.1002/ange.200503678
10.1016/0040-4020(76)80045-2
For isolation of trichodimerol:
10.1139/v92-320
10.1021/ol991070h
10.1152/physrev.2000.80.4.1483
10.1046/j.1365-3083.2003.01221.x
{'key': 'e_1_2_3_52_2', 'first-page': '726', 'author': 'King F. E.', 'year': '1942', 'journal-title': 'J. Chem. Soc.'} / J. Chem. Soc. by King F. E. (1942)
10.1021/op100291g
10.3891/acta.chem.scand.23-2515
10.1002/cber.19671000915
CCDC 1022042 (dibefurin) and CCDC 1022044 (14) contain the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre viawww.ccdc.cam.ac.uk/data_request/cif.
Two equivalents of13were employed one for sacrificial oxidation and the other for the desired dimerization.
Related tautomerizations of quinones to quinone methides have been described:
10.1039/p19860001627
10.1002/zaac.200900282
10.1021/ol801499s
10.1021/ja042375g
10.1021/ol052472u
10.1021/ja803498r
10.1021/ol102157d
10.1002/chem.201103605
10.1007/s11172-007-0045-9
Intriguingly a small number of diterpenoid and triterpenoid natural products are formed by hetero‐Diels–Alder dimerization after oxidation of their catechol moiety:
10.1016/0040-4020(94)00999-B
10.1016/0040-4020(96)00497-8
10.1021/np9900728
10.1016/j.bmc.2007.11.008
10.1016/j.tetlet.2005.09.104

Dates

Type	When
Created	10 years, 9 months ago (Nov. 4, 2014, 3:50 p.m.)
Deposited	1 year, 10 months ago (Oct. 17, 2023, 6:30 p.m.)
Indexed	1 year, 2 months ago (May 30, 2024, 7:09 p.m.)
Issued	10 years, 9 months ago (Nov. 4, 2014)
Published	10 years, 9 months ago (Nov. 4, 2014)
Published Online	10 years, 9 months ago (Nov. 4, 2014)
Published Print	10 years, 8 months ago (Dec. 1, 2014)

Funders 0

None

BibTeX

@article{Ellerbrock_2014, title={Biomimetic Synthesis of the Calcineurin Phosphatase Inhibitor Dibefurin}, volume={126}, ISSN={1521-3757}, url={http://dx.doi.org/10.1002/ange.201407088}, DOI={10.1002/ange.201407088}, number={49}, journal={Angewandte Chemie}, publisher={Wiley}, author={Ellerbrock, Pascal and Armanino, Nicolas and Trauner, Dirk}, year={2014}, month=nov, pages={13632–13636} }

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