No abstract

No abstract

Acidic condensation of 2,4-dimethylfuran with acetaldehyde provided 2,2-ethylidenebis[3,5-dimethylfuran] (7) which added 1 equiv. of methyl bromopropynoate to give a major adduct 8. Regio-and stereoselective hydroboration of the latter 7-oxanorbornadiene derivative followed by alcohol protection and methanolysis of its P-bromoacrylate moiety gave (1 RS,2RS,4RS,SSR,6SR, 1'RS)-methyl 4-[l'-(3",5"-dirnethylfuran-2"-yl)ethyl]-3,3-dimethoxy-6-exo -[(2-methoxy)ethoxy]-1,5-endo-dimethyl-7-oxabicyclo[2.2.l]heptane-2-endo -carboxylate (24) (Schemes 2 and 3). Reduction of 24 with LiAIH,, followed by H,O and MeOH elimination gave the 3-methylidene-7-oxanorbornan-2-one derivative 26 which underwent 7-oxa ring opening through a SJ' type of reaction with Me2CuLi (Scheme 4). Stereoselective hydrogenation and ketone reduction provided (1RS,2SR,3RS,4RS, [2]). In 1956, Woodward [3] described these compounds as 'hopelessly complex' for synthesis. Since then, several methods and strategies have been developed to provide access to these systems which possess a large number of stereogenic centres [4] (see also ref. 4-16 in [21). During the seventies and eighties, the carbohydrate approach was the most popular to construct these acyclic chains. More recently, the advent of new chiral auxiliaries [5] and chirons [6], as well as the development of new techniques to control the diastereoselectivity of aldehyde nucleophilic additions [7] and cross-aldolization [8], made possible the total, asymmetric synthesis of a large number of polypropionate natural products and analogues [9]. Other approaches imply two-directional chain elongation and a 'desymmetrization' process [ 101. Bicyclic alkenes and ketones that display high facial selectivity in their reactions for steric reasons have also been used as starting materials [ll-181. We have shown [19] that the Zn1,-catalyzed Diels-Alder addition of 2,4-dimethylfuran to 1 -cyanovinyl (1R)-camphanate leads to optically pure adduct (+)-1 in high yield, the saponification of which furnishes enone (+)-2 and allows one

No abstract

This theoretical study focuses on two indole derivatives, melatonin (1) and carvedilol (8). with the objective of improving our understanding of the molecular mechanisms underlying their radical-scavenging activity. Quantum-mechanical calculations were carried out using the AM1 semi-empirical method, some results being conlirmed by nh initio (3-21'3) calculations. The quantum-chemical descriptor AH,, (relative adiabatic oxidation potential) and the shape of the SOMO (singly occupied molecular orbital) indicate that the stabilization of its radical cation can partially explain the well-documented antioxidant efficacy of melatonin. This stabilization may result froin electrostatic interactions and from a hyperconjugative effect existing in a family of conformers of the melatonin radical cation having the side chain almost perpendicular to the plane of the aromatic rings. Furthermore, 6-hydroxymelatonin (7) appears to be a better free-radical scavenger than melatonin (1) in agreement with experimentel results. According to the theoretical parameters AH", and AHab, (relative bond dissociation enthalpy). carvedilol (8) is not a good antioxidant, in contrast to its ring-hydroxylated metabolites whose powerful antioxidant effects are explained by the formation of an oxyl radical stabilized by delocalization over the carbazole nucleus.