Synthesis of Analogues of (−)-Cytisine for in Vivo Studies of Nicotinic Receptors Using Positron Emission Tomography

Abstract

[formula: see text] 9-Substituted analogues of (-)-cytisine were synthesized in high yields via palladium-mediated couplings of either 9-(-)-bromocytisine and organostannanes or 9-(-)-trimethylstannylcytisine and fluorobromobenzene. The protection of the amine with a nitroso group and the use of PdCl2(PPh3)2 to carry out the Stille reaction allowed the rapid synthesis of 9-(4'-[18F]fluorophenyl)cytisine (18F: t1/2 = 109.7 min), a new promising radioligand (radiochemical yield: 10% from [18F]KF, 150 min, four steps) for positron emission tomography studies of alpha 4 beta 2 nicotinic receptors.

Synthesis of 4‐[18F]fluoroiodobenzene and its application in sonogashira cross‐coupling reactions

“…However, only a few attempts have been made to adopt the recent advances in transition-metal catalysed reactions to the synthesis of 18 Flabelled radiotracers. [7][8][9][10] The palladium-catalysed cross-coupling reactions of organometallic compounds like Grignard reagents, tin, or boron derivatives with organic halides suggests the use of 18 F-labelled aryl halides as the coupling partners. This approach can be regarded as a general method for the mild and efficient introduction of a 4-[ 18 F]fluorophenyl group into a wide variety of complex functionalized target molecules.…”

“…The beneficial effect of a fluoroaryl group in drug design and development with regard to drug metabolism, in vivo activity and stability has been reviewed recently. 11,12 The first few reports on the synthesis of 18 F-labelled radiotracers via palladium-mediated cross-coupling reactions have mainly exploited the Stille reaction [7][8][9] and in one case a HartwigBuchwald N-arylation reaction. 10 …”

Synthesis of18F-labelled biphenyls via SUZUKI cross-coupling with 4-[18F]fluoroiodobenzene

“…A wide variety of palladium complexes can be used for Suzuki cross-coupling reactions. Palladium(0) complexes Pd(PPh 3 ) 4 and Pd 2 (dba) 3 are frequently used, but Pd(PPh 3 ) 2 Cl 2 and Pd(OAc) 2 plus PPh 3 are also known to be efficient.…”

Synthese von 11C‐, 18F‐, 15O‐ und 13N‐Radiotracern für die Positronenemissionstomographie

“…Die ersten Versuche mit dem Wildtyp-Enzym ergaben niedrige RCYs von ca. 1 %, [223] [228] Wüst und Kniess [229] berichteten über palladiumvermittelte Sonogashira-Kupplungen von 75 zur Bildung einer Serie terminaler Alkine (Schema 49), die eine Hydroxygruppe enthalten konnten.…”