A flexible synthetic strategy enabling preparation of novel forskolin analogues
Paweł Marcin Szczepanik a, b
; Andrey Mikhaylov a, b
; Jakub Švenda*, a, b
a
Masaryk University, Faculty of Science, Department of Chemistry, Kamenice 5/A8,
623 00 Brno, Czech Republic
b
International Clinical Research Center, St. Anne’s University Hospital Brno, Pekařská 53,
656 91 Brno, Czech Republic
*svenda@chemi.muni.cz
Forskolin is a natural product commonly used in biomedical research as a reagent to
increase levels of cyclic AMP (cyclic adenosine monophosphate)
by stimulation of enzyme adenylyl cyclase[1]
.
Aim of our work is to develop a flexible synthetic route that would enable preparation of novel
forskolin analogues not accessible by semisynthesis or published fully synthetic approaches.[2-6]
.
Structure of forskolin presents a considerable challenge for synthesis, because of high level of
oxidation, dense substitution and rich stereochemistry. Using a convergent approach (strategic
bonds in red), we would like to flexibly alter the structure of this natural product at novel positions
simply by choice of the building blocks.
Literature
[1] Sadana, R.; Dessauer C. W. Physiological Roles for G Protein-Regulated Adenylyl Cyclase Isoforms: Insights from Knockout and
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[2] Ziegler, F. E.; Jaynes, B. H.; Saindane, M. T. A Synthetic Route to Forskolin J. Am. Chem. Soc. 1987, 109 (26), 8115–8116.
[3] Hashimoto, S.; Sakata, S.; Sonegawa, M.; Ikegami, S. A Total Synthesis of (±)-Forskolin J. Am. Chem. Soc. 1988, 110 (11), 3670–3672.
[4] Corey, E. J.; Jardine, P. da S.; Rohloff, J. C. Total Synthesis of (±)-Forskolin J. Am.Chem. Soc. 1988, 110 (11), 3672–3673.
[5] Delpech, B.; Calvo, D.; Lett, R. Total Synthesis of Forskolin — Part I Tetrahedron Lett. 1996, 37 (7), 1015–1018.
[6] Hylse, O.; Maier, L.; Kučera, R.; Perečko, T.; Svobodová, A.; Kubala, L.; Paruch, K.; Švenda, J. A Concise Synthesis of Forskolin Angew.Chem.
Int. Ed. 2017, 56 (41), 12586–12589.