6 research outputs found
Organocatalytic tandem Michael addition reactions: A powerful access to the enantioselective synthesis of functionalized chromenes, thiochromenes and 1,2-dihydroquinolines
Enantioselective organocatalysis has become a field of central importance within asymmetric chemical synthesis and appears to be efficient approach toward the construction of complex chiral molecules from simple achiral materials in one-pot transformations under mild conditions with high stereocontrol. This review addresses the most significant synthetic methods reported on chiral-amine-catalyzed tandem Michael conjugate addition of heteroatom-centered nucleophiles to α,β-unsaturated compounds followed by cyclization reactions for the enantioselective construction of functionalized chiral chromenes, thiochromenes and 1,2-dihydroquinolines in optically enriched forms found in a myriad of bioactive natural products and synthetic compounds
14,15-Epoxyeicosa-5,8,11-trienoic Acid (14,15-EET) Surrogates: Carboxylate Modifications
The cytochrome P450 eicosanoid 14,15-epoxyeicosa-5,8,11-trienoic
acid (14,15-EET) is a powerful endogenous autacoid that has been ascribed
an impressive array of physiologic functions including regulation
of blood pressure. Because 14,15-EET is chemically and metabolically
labile, structurally related surrogates containing epoxide bioisosteres
were introduced and have become useful in vitro pharmacologic tools
but are not suitable for in vivo applications. A new generation of
EET mimics incorporating modifications to the carboxylate were prepared
and evaluated for vasorelaxation and inhibition of soluble epoxide
hydrolase (sEH). Tetrazole <b>19</b> (ED<sub>50</sub> 0.18 ÎĽM)
and oxadiazole-5-thione <b>25</b> (ED<sub>50</sub> 0.36 ÎĽM)
were 12- and 6-fold more potent, respectively, than 14,15-EET as vasorelaxants;
on the other hand, their ability to block sEH differed substantially,
i.e., 11 vs >500 nM. These data will expedite the development of
potent
and specific in vivo drug candidates