11 research outputs found
Design and Synthesis of 4-Alkylidene-b-lactams: Benzyland Phenethyl-carbamates as Key Fragments to Switch on Antibacterial Activity
The emergence of multidrug-resistant bacterial strains is particularly
important in chronic pathologies such as cystic fibrosis
(CF), in which persistent colonization and selection of resistant
strains is favored by the frequent and repeated use of antibacterial
agents. Staphylococcus aureus is a common pathogen in
CF patients that has an associated increased multidrug resistance.
In previous studies we demonstrated that the presence
of a 4-alkylidene side chain directly linked to a beta-lactam appeared
to strengthen the potency against S. aureus, especially
against methicillin-resistant S. aureus (MRSA) strains. In the
present study, 21 new 4-alkylidene-beta-lactams were synthesized
and evaluated for antibacterial activity. We designed the new
compounds to have aryl, benzyl, or phenethyl-carbamate
groups on the C3 hydroxyethyl side chain. We found a correlation
between biological activity and the nitrogen substituent
of the carbamate group, and two phenethyl-carbamate b-lactams
were shown to be valuable antibacterial agents against
selected linezolid-resistant strains, with a minimum inhibitory
concentrations of 2–4 mgL-1
Enantioselective Total Synthesis of (+)-Gephyrotoxin 287C
A synthesis of (+)-gephyrotoxin 287C using, (S)-phenylglycinol-derived tricyclic lactam 7 as the starting enantiomeric scaffold is reported. From the stereochemical standpoint, the key steps are the generation of the DHQ C-5 stereocenter by hydrogenation of the C-C double bond, removal of the chiral inductor to give a cis-DHQ introduction of the DHQ C-2 substituent, completion of the (Z)-enyne moiety, and generation of the C-1 stereocenter during closure of the pyrrolidine ring
Studies on the Synthesis of Phlegmarine-Type Lycopodium Alkaloids: Enantioselective Synthesis of (−)-Cermizine B, (+)-Serratezomine E, and (+)-Luciduline
The synthesis of the Lycopodium alkaloids, (-)-cermizine B, (+)-serratezomine E, and (+)-luciduline using phenylglycinol-derived tricyclic lactams as chiral scaffolds, is reported. The requisite lactams are prepared by a cyclocondensation reaction between ( R)- or ( S)-phenylglycinol and the substituted δ-keto ester 11, easily accessible from ( R)-pulegone. The factors governing the stereoselectivity of these cyclocondensation reactions are discussed. Key steps of the synthesis from the stereochemical standpoint are the stereoselective elaboration of the allyl substituent to the ( S)-2-(piperidyl)methyl moiety and the stereoselective removal of the chiral inductor to give a cis-decahydroquinoline
Total Synthesis of (−)-Cylindricine H
Starting from (R)-phenylglycinol-derived tricyclic lactam 1, the enantioselective synthesis of (−)-cylindricine H is reported. From the stereochemical standpoint, the key steps are the stereoselective generation of the quaternary C10 stereocenter, the stereoselective introduction of the C4 acetoxy and C2 butyl substituents taking advantage of the lactam carbonyl functionality, and the assembly of the pyrrolidine ring with the required functionalized one-carbon chain at C13 by intramolecular opening of an epoxide
Enantioselective Total Synthesis of (+)-Gephyrotoxin 287C
A synthesis of (+)-gephyrotoxin 287C using, (S)-phenylglycinol-derived tricyclic lactam 7 as the starting enantiomeric scaffold is reported. From the stereochemical standpoint, the key steps are the generation of the DHQ C-5 stereocenter by hydrogenation of the C-C double bond, removal of the chiral inductor to give a cis-DHQ introduction of the DHQ C-2 substituent, completion of the (Z)-enyne moiety, and generation of the C-1 stereocenter during closure of the pyrrolidine ring
Enantioselective Total Synthesis of (+)-Gephyrotoxin 287C
A synthesis of (+)-gephyrotoxin 287C using, (S)-phenylglycinol-derived tricyclic lactam 7 as the starting enantiomeric scaffold is reported. From the stereochemical standpoint, the key steps are the generation of the DHQ C-5 stereocenter by hydrogenation of the C-C double bond, removal of the chiral inductor to give a cis-DHQ introduction of the DHQ C-2 substituent, completion of the (Z)-enyne moiety, and generation of the C-1 stereocenter during closure of the pyrrolidine ring
Studies on the Synthesis of Phlegmarine-Type Lycopodium Alkaloids: Enantioselective Synthesis of (−)-Cermizine B, (+)-Serratezomine E, and (+)-Luciduline
The synthesis of the Lycopodium alkaloids, (-)-cermizine B, (+)-serratezomine E, and (+)-luciduline using phenylglycinol-derived tricyclic lactams as chiral scaffolds, is reported. The requisite lactams are prepared by a cyclocondensation reaction between ( R)- or ( S)-phenylglycinol and the substituted δ-keto ester 11, easily accessible from ( R)-pulegone. The factors governing the stereoselectivity of these cyclocondensation reactions are discussed. Key steps of the synthesis from the stereochemical standpoint are the stereoselective elaboration of the allyl substituent to the ( S)-2-(piperidyl)methyl moiety and the stereoselective removal of the chiral inductor to give a cis-decahydroquinoline
Studies on the Synthesis of Phlegmarine-Type Lycopodium Alkaloids: Enantioselective Synthesis of (−)-Cermizine B, (+)-Serratezomine E, and (+)-Luciduline
The synthesis of the Lycopodium alkaloids, (-)-cermizine B, (+)-serratezomine E, and (+)-luciduline using phenylglycinol-derived tricyclic lactams as chiral scaffolds, is reported. The requisite lactams are prepared by a cyclocondensation reaction between ( R)- or ( S)-phenylglycinol and the substituted δ-keto ester 11, easily accessible from ( R)-pulegone. The factors governing the stereoselectivity of these cyclocondensation reactions are discussed. Key steps of the synthesis from the stereochemical standpoint are the stereoselective elaboration of the allyl substituent to the ( S)-2-(piperidyl)methyl moiety and the stereoselective removal of the chiral inductor to give a cis-decahydroquinoline
Stereocontrolled access to enantiopure to enantiopure 7-substituted cis- and trans-octahydroindoles
Cyclocondensation of (R)-phenylglycinol with stereoisomeric mixtures (racemates, cis/trans) of 3-substituted 2- oxocyclohexaneacetates stereoselectively afforded tricyclic oxazoloindolone lactams, from which straightforward procedures for the stereocontrolled formation of enantiopure 7-substituted octahydroindoles with a variety of stereochemical patterns have been developed. The methodology has been successfully applied to the synthesis of (+)-α-lycorane