Lactams as prostanoid receptor ligands. Part 4: 2-Piperidones as selective EP4 receptor agonists

Asymmetric Synthesis of 6-Alkyl- and 6-Arylpiperidin-2-ones. Enantioselective Synthesis of (S)-(+)-Coniine

“…Piperidinones are somewhat less prominent but very often they serve a role as advanced intermediates prior to their conversion to piperidines. 2c, In this context the corresponding saturated or unsaturated δ-lactams have emerged as powerful tools as they possess the requisite structure and functional group locations for further elaboration to synthetic targets, particularly piperidine alkaloids. The subsequent introduction of substituents on the carbon atoms of the piperidine ring may indeed be achieved by α-amidoalkylation, enolate or homoenolate alkylations, manipulation of the amide carbonyl group, and functionalization of the olefinic moiety including but not limited to epoxydation or dihydroxylation . The substituted piperidin-2-ones are also substructural units of barbiturates and glutarimides and are key intermediates for the synthesis of aminopentanoic acids .…”

“…These highly functionalized precursors are usually equipped with chiral auxiliaries derived from the natural chiral pool or with tailor-made stereocontrolling agents. They also have been obtained by reductive opening of diastereochemically pure oxazolopiperidones 15 or via an asymmetric amidoalkylation involving interception of variously generated chiral iminium salts with silyl derivatives 16 or cyanocuprates. 5c, On the other hand, studies on the corresponding α,β- or γ,δ-unsaturated δ-lactams are scarce and most of the chiral 6-substituted models have been assembled from the corresponding saturated lactams by a multistep sequence involving metalation/electrophilic capture with phenylselenyl bromide/oxidation reactions followed by an ultimate elimination reaction.…”

Synthesis of fluorofurans and perfluoroalkylfurans

“…The effect of the derivative 2 is similar to that of Docetaxel (Taxotere 1 ), which is used in cancer chemotherapy for the treatment of advanced ovarian and breast cancer [14]. Trifluoromethylfuran 3 is an agonist of the EP prostanoids [15]. The derivative 4 is an antagonist of oxytocin, a well-known agent for stimulating contractility in human myometrium that is widely used for the induction of labour [16].…”

Synthesis of 3-Amino-5-fluoroalkylfurans by Intramolecular Cyclization

“…Furans make up a very important class of heterocycles and can be found in natural products, in pharmaceutical and agrochemical molecules, and as intermediates in organic chemistry. − Fluorinated furans can have enhanced biological properties, and their use in drugs and pesticides has often been described. − For instance, furans, usually poorly stable under acidic conditions, can be stabilized by a fluorinated group, due to its strong electron withdrawing property. Those structures can be synthesized using two different strategies.…”