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.Phenylglycinol-and other aminoalcohol-derived oxazolopiperidone and oxazoloquinolone lactams have proven to be versatile building blocks for the enantioselective synthesis of a wide variety of diversely substituted piperidine-containing heterocycles, including complex alkaloids belonging to different skeletal types. 1 The usefulness of these lactams lies in their easy preparation, by stereoselective cyclocondensation of the chiral nonracemic aminoalcohol with an appropriate δ-oxo acid derivative, and in their functionalization and conformational rigidity, which allow the stereocontrolled formation of C-C bonds at the different positions of the nitrogen heterocycle.Starting from 2-oxocyclohexanepropionate-based δ-keto esters, the cyclocondensation stereoselectively affords tricyclic oxazoloquinolone lactams, which can be easily converted to enantiopure cis-decahydroquinoline alkaloids. 2 Depending on the structural characteristics of the substrate, the cyclocondensation involves a dynamic kinetic resolution and/or differentiation of enantiotopic or diastereotopic ester groups.Bearing in mind that the octahydroindole nucleus is present in numerous natural bioactive compounds, for instance Amaryllidaceae alkaloids, we considered expanding the scope of the above stereoconvergent cyclocondensation reactions towards the generation of tricyclic oxazoloindolone lactams as precursors of this nucleus. This would require starting from appropriately substituted 2-oxocyclohexaneacetate derivatives (γ-instead of δ-keto esters).In this letter, we report a general straightforward procedure for the stereocontrolled access to enantiopure 7-substituted cis-and trans-octahydroindoles. The few precedents of the enantioselective synthesis of 7-substituted octahydroindoles all deal with 7-aryl cis-derivatives, 3 used as intermediates in the synthesis of lycorane-like structures. Scheme 1. Envisaged Access to Enantiopure 7-Substituted OctahydroindolesThe preparation of the target enantiopure octahydroindoles was envisaged as outlined in Scheme 1. Starting from a stereoisomeric mixture of 3-substituted 2-oxocyclohexane-acetates 1 (two racemates when R = alkyl or aryl; one racemate and a

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.

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.

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 β-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-β-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 β-lactams were shown to be valuable antibacterial agents against selected linezolid-resistant strains, with a minimum inhibitory concentrations of 2-4 mg L .

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 C 10 stereocenter, the stereoselective introduction of the C 4 acetoxy and C 2 butyl substituents taking advantage of the lactam carbonyl functionality, and the assembly of the pyrrolidine ring with the required functionalized one-carbon chain at C 13 by intramolecular opening of an epoxide.