Synlett 2014; 25(4): 556-558
DOI: 10.1055/s-0033-1340495
letter
© Georg Thieme Verlag Stuttgart · New York

Iridium-Catalysed C–H Borylation Facilitates a Total Synthesis of the HRV 3C Protease Inhibitor (±)-Thysanone

Katrin Schünemann
a  School of Chemical Sciences, The University of Auckland, 23 Symonds St., Auckland 1142, New Zealand   Fax: +64(9)3737422   Email: m.brimble@auckland.ac.nz
b  Department of Molecular Medicine and Pathology, The University of Auckland, 85 Park Road, Auckland 1142, New Zealand
,
Daniel P. Furkert
a  School of Chemical Sciences, The University of Auckland, 23 Symonds St., Auckland 1142, New Zealand   Fax: +64(9)3737422   Email: m.brimble@auckland.ac.nz
,
Stephen Connelly
c  Department of Molecular Biology, The Scripps Research Institute, BCC 265, 10550 Torrey Pines Road, La Jolla, CA 92037, USA
,
John D. Fraser
b  Department of Molecular Medicine and Pathology, The University of Auckland, 85 Park Road, Auckland 1142, New Zealand
,
Jonathan Sperry
a  School of Chemical Sciences, The University of Auckland, 23 Symonds St., Auckland 1142, New Zealand   Fax: +64(9)3737422   Email: m.brimble@auckland.ac.nz
,
Margaret A. Brimble*
a  School of Chemical Sciences, The University of Auckland, 23 Symonds St., Auckland 1142, New Zealand   Fax: +64(9)3737422   Email: m.brimble@auckland.ac.nz
› Author Affiliations
Further Information

Publication History

Received: 14 October 2013

Accepted after revision: 02 December 2013

Publication Date:
10 January 2014 (online)


Abstract

A new total synthesis of the HRV 3C protease inhibitor (±)-thysanone is described. The synthetic route hinges on an iridium-catalysed borylation to install the resorcinol-derived component of the natural product.

Supporting Information

 
  • References and Notes

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  • 9 To a mixture of (±)-1-deoxythysanone (13 mg, 50 μmol) in CCl4 (8 mL) was added bromine (50 μL, 1 M in CCl4, 50 μmol). The mixture was heated at reflux under irradiation with a desk lamp for 30 min. The mixture was concentrated in vacuo, and THF (1 mL) and H2O (0.5 mL) were added. The resulting mixture was stirred for 1 h at r.t. Then CH2Cl2 (5 mL) and H2O (5 mL) were added. The aqueous layer was extracted with CH2Cl2 (3 × 100 mL/mmolSM). The combined organic extracts were washed with brine (5 mL) and dried with MgSO4. The solvent was removed in vacuo, and the residue was purified by preparative TLC (SiO2, toluene–ethyl formate–formic acid = 50:49:1) to afford the title compound (6.09 mg, 22 μmol, 44%) as a yellow solid. 1H NMR (400 MHz, acetone-d 6): δ = 12.26 (1 H, s, OH), 9.93 (1 H, s, OH), 7.08 (1 H, d, J = 2.4 Hz, H-6), 6.62 (1 H, d, J = 2.4 Hz, H-8), 5.91 (1 H, dd, J = 18.2, 5.8 Hz, H-1), 4.39–4.29 (1 H, m, H-3), 2.70 (1 H, dd, J = 19.2, 3.4 Hz, H-4A), 2.18–2.08 (1 H, m, H-4B), 1.31 (3 H, d, J = 6.3 Hz, H-Me), lactol OH not observed. Rf = 0.74 (hexanes–EtOAc, 1:2). The spectroscopic data were in agreement with those reported4c in the literature.