0000000000162198
AUTHOR
André Fischer
Synthesis and PET studies of [11C-cyano]letrozole (Femara®), an aromatase inhibitor drug
Abstract Introduction Aromatase, a member of the cytochrome P 450 family, converts androgens such as androstenedione and testosterone into estrone and estradiol, respectively. Letrozole (1-[bis-(4-cyanophenyl)methyl]-1 H -1,2,4-triazole; Femara) is a high-affinity aromatase inhibitor ( K i =11.5 nM) that has Food and Drug Administration approval for breast cancer treatment. Here we report the synthesis of carbon-11-labeled letrozole and its assessment as a radiotracer for brain aromatase in the baboon. Methods Letrozole and its precursor (4-[(4-bromophenyl)-1 H -1,2,4-triazol-1-ylmethyl]benzonitrile) were prepared in a two-step synthesis from 4-cyanobenzyl bromide and 4-bromobenzyl bromide,…
Stereoselektive Synthese enantiomerenreiner Nupharamin-Alkaloide aus dem Castoreum (Bibergeil)
Tierische Parfumalkaloide: Eine stereoselektive Mannich-Michael-Reaktion an N-Galactosylfurylaldimin zu 1 (Piv = Pivaloyl), anschliesende konjugierte Cuprataddition und stereoselektive Protonierung des gebildeten Enolats, alle kontrolliert vom Kohlenhydrat, ermoglichen erstmals die Totalsynthese des all-cis-Nupharamins 2 aus dem Castoreum. Enolatprotonierung nach Abspaltung des Kohlenhydrats fuhrt alternativ zum Epimer 3.
Stereoselective Synthesis of Enantiomerically Pure Nupharamine Alkaloids from Castoreum
An animalic note: The first total synthesis of the all-cis nupharamine 2, an alkaloid from beaver castoreum, is based on the stereoselective domino Mannich-Michael reaction of N-galactosylfurylaldimine to give 1 (Piv = pivaloyl), subsequent conjugate cuprate addition, and stereoselective protonation of the enolate. These reactions are all controlled by the carbohydrate. Protonation of the enolate after cleavage of the auxiliary leads to epimer 3.