ABSTRACT
The convergent and selective preparation of (Z)-monofluoroalkene-based dipeptide isosteres from functionalized fluorosulfones as a cornerstone is described. In this approach, the N-terminal amino group is introduced by a conjugate addition reaction of phthalimide onto fluorinated vinylsulfones containing α-amino-acid side chains while the C-terminal motif is linked to the fluorovinylic peptide bond mimic via the Julia-Kocienski reaction between fluorosulfones and substituted aldehydes bearing α-amino-acid side chains.
Subject(s)
PeptidomimeticsABSTRACT
A series of fluorine and non-fluorine-substituted C-glucosylidenes (exo-glucals) has been synthesized via a modified Julia olefination. The deprotected exo-glucals were prepared in five steps from commercially available d-gluconolactone. The evaluation of this original family of compounds against a panel of glycosidases showed a highly specific in vitro activity towards mammalian ß-glucosidase depending on the double bond substituents.
Subject(s)
Alkenes/chemistry , Enzyme Inhibitors/pharmacology , Monosaccharides/pharmacology , beta-Glucosidase/antagonists & inhibitors , Dose-Response Relationship, Drug , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/chemistry , Glycosides , Molecular Structure , Monosaccharides/chemical synthesis , Monosaccharides/chemistry , Saccharomyces cerevisiae/enzymology , Structure-Activity Relationship , beta-Glucosidase/metabolismABSTRACT
Convenient access to homochiral fluoroalkenes is described via a Julia-Kocienski olefination reaction. The required homochiral fluorosulfone is synthesized by a Mitsunobu reaction from readily available enantiopure secondary alcohols.
Subject(s)
Alkenes/chemistry , Hydrocarbons, Fluorinated/chemistry , Hydrocarbons, Fluorinated/chemical synthesis , Alcohols/chemistry , Alkylation , Fluorides/chemistry , Molecular Structure , Stereoisomerism , Sulfuric Acids/chemistryABSTRACT
The use of aryl triflates as reaction partners in a palladium-catalyzed domino direct arylation/N-arylation provides a great advantage due to the availability of starting materials. Furthermore, it allows expedient access to biologically interesting benzo[c]phenanthridine alkaloids.