Multidrug resistance (MDR) mediated by P-glycoprotein (Pgp) remains the major obstacle for successful treatment of cancer. Inhibition of Pgp transport is important for higher efficacy of anticancer drugs. Lipophilic cationogenic amines with at least one tertiary N atom, such as verapamil, are classical PgP-blocking agents. In a search for novel accessible compounds potent against MDR tumor cells, we synthesized a series of arylalkylamines that contain isoprenoid side chains of different length. Two out of seven new analogues of the known N,N'-bis(3,4-dimethoxybenzyl)-N-solanesylethylenediamine (SDB-ethylenediamine), namely, compounds with C10 and C15 side chains, at low micromolar concentrations were preferentially toxic for several mammalian tumor cell lines that acquired MDR during prolonged drug selection. Moreover, at noncytotoxic concentrations, these compounds potently sensitized MDR cells to Pgp substrates vinblastine and adriamycin. We conclude that these analogues of SDB-ethylenediamine may have dual therapeutic advantage because (i) they are preferentially toxic for MDR cells when administered alone and (ii) they potentiate the cytotoxicity of Pgp-transported anticancer drugs.

The first primary amine-derived organocatalyst modified with an ionic group for asymmetric Michael reactions of C-nucleophiles with a,b-unsaturated ketones was synthesized. In the presence of this catalyst and an acidic co-catalyst (AcOH), hydroxycoumarin and its sulfur-containing analogue reacted with benzylideneacetone derivatives or cyclohexenone to afford the corresponding Michael adducts in high yields (up to 97%) and with reasonable enantioselectivity (up to 80%). The catalyst could be easily recovered and efficiently reused three times, afterwards, its activity and stereodifferentiating ability gradually declined. The analysis of recovered catalyst samples by ESI-MS allowed us to detect undesirable side reactions that poisoned the catalyst, and propose an approach for its reactivation.

The first "green" asymmetric organocatalytic reaction in a supercritical carbon dioxide medium was elaborated. Under the proposed conditions (100 bar, 35 °C), α-nitroalkenes enantioselectively accept diphenylphosphite in the presence of bifunctional organocatalysts bearing the tertiary amino group and the squaramide fragment to afford corresponding β-nitrophosphonates in high yields and with enantioselectivities of up to 94% ee. By varying the catalyst structure it is possible to synthesize both β-nitrophosphonate enantiomers under these conditions. A significant potential of the supercritical extraction for product isolation and catalyst recovery was demonstrated. † Electronic supplementary information (ESI) available. See

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In the amine-catalyzed reactions of prenal with (Z)-5-methyl-2-(methoxycarbonyl)hexa-2,4-dienoic or (Z%3-phenyl-2-(ethoxycarbonyl)prop-2-enoic acid chiral 13-amino alcohols provide for higher enantiomeric purity of the resulting alkyl 4-methyl-6-(2-methylprop-1-enyl)-and 4-methyl-6-phenylcyclohexa-l,3-dienoates than that provided by related chiral amines without hydroxy group. The vatues of ee attained in nonpolar solvents are higher than those observed in the polar ones. Substituting stoichiometric amounts of a chiral 1-amino-3-methylbuta-l,3-diene for a combination of prenal with 0.1 equiv, of the corresponding chirat amine results in the products of much lower enantiomeric purity.Key words: 3-methylbut-2-enal, chiral secondary amines and hydroxy amines; chiral dienamines; monoalkyl ylidenemalonates; net enantioselectivity.Employing homochiral 2-amino-1,3-dienes in asymmetric Diels--Alder cycloaddition reactions 1,2 involves preparing them preliminarily. On the other hand, chiral six-membered carbocycles can be obtained following the same pattern, but in a single step, by generating a chiral l-amino-l,3-diene from a branched ct,13-enal A and a chiral secondary amine in the presence of an atkyl hydrogen ylidenemalonate as the dienopile. 3 Then the nascent dieneamine B eycloadds to the dienophile C to give unstable 13-amino acids D which readily release CO 2 (this makes the whole process irreversible) and leave a chiral cyclohexadiene E and the starting chiral amine which re-enters the catalytic cycle (Scheme 1).Here we report on the effects of the structure and absolute configuration of chiral amines on the net enantioselectivity (NES) and its trend in the aminecatalyzed asymmetric synthesis of methyl 4-methyl-6-(2-methylprop-1 -enyl)cyclohexa-1,3-dienecarboxylate (1) or ethyl 4-methyl-6-phenylcyclohexa-l,3-dienecarboxylate (2) from prenal (3) and 5-methyl-2-(methoxycarbonyl)hexa-2,4-dienoic (4) or 5-methyl-2-(ethoxycarbonyl)prop-2-enoie acid (5), respectively.* All experiments were carried out using crystalline monoesters 4 and 5 consisting entirely of the Z isomers (according to 1H NMR data, cf Ref. 4), which makes * In fact, the formation of compounds I and 2 involves two diastereoselective steps, that is, the formation and fragmentation of the corresponding cycloadducts of the type D. Hence, as a matter of convenience, the stereochemical outcome of the whole process should be termed net enantioselectivity.

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