English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT

Released

Journal Article

Synthesis and Biological Evaluation of Nonylprodigiosin and Macrocyclic Prodigiosin Analogues

MPS-Authors
/persons/resource/persons58380

Fürstner,  Alois
Research Department Fürstner, Max-Planck-Institut für Kohlenforschung, Max Planck Society;

/persons/resource/persons58586

Grabowski,  Jaroslaw
Research Department Fürstner, Max-Planck-Institut für Kohlenforschung, Max Planck Society;

/persons/resource/persons58744

Lehmann,  Christian W.
Service Department Lehmann (EMR), Max-Planck-Institut für Kohlenforschung, Max Planck Society;

External Ressource
No external resources are shared
Fulltext (public)
There are no public fulltexts stored in PuRe
Supplementary Material (public)
There is no public supplementary material available
Citation

Fürstner, A., Grabowski, J., Lehmann, C. W., Kataoka, T., & Nagai, K. (2001). Synthesis and Biological Evaluation of Nonylprodigiosin and Macrocyclic Prodigiosin Analogues. ChemBioChem: A European Journal of Chemical Biology, 2(1), 60-68. doi:10.1002/1439-7633(20010105)2:1<60:AID-CBIC60>3.0.CO;2-P.


Cite as: http://hdl.handle.net/11858/00-001M-0000-0024-34D4-8
Abstract
Nonylprodigiosin (4) and various of its analogues have been prepared by Suzuki cross-coupling reactions of a well accessible pyrrolyl triflate with (hetero)aryl boronic acid derivatives bearing alkenyl side chains. The resulting alkenes or dienes were subjected to metathesis dimerization or ring-closing metathesis (RCM) reactions, respectively, by using a ruthenium indenylidene complex as the catalyst. The biological activity of the products thus obtained was tested in two different assays monitoring i) the proliferation of murine spleen cells induced by lipopolysaccharides (LPS) and concanavalin A (Con A), and ii) the vacuolar acidification of baby hamster kidney (BHK) cells. Compounds 4 and 21 suppressed Con A-induced T-cell proliferation much more potently than LPS-induced B-cell proliferation. Furthermore, compounds 4 and 26 markedly inhibited vacuolar acidification, although other compounds exhibited no or only marginal effects. Thus, the immunosuppressive activity of prodigiosins toward T-cell proliferation seems to be mediated through cellular targets distinct from vacuolar acidification, and the prodigiosin analogues might be powerful tools to dissect these biological responses. The X-ray crystal structure of the macrocyclic product 25 has been determined, showing that the replacement of one pyrrole ring of the parent compound 4 by a phenyl group does not alter the overall electronic features of the remaining heterocyclic ring system of these alkaloids.