Preparation of (S)-2-Allyl-2-methylcyclohexanone (Cyclohexanone, 2-methyl-2-(2-propen-1-yl)-, (2S)-)

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Preparation of (S)-tert-ButylPHOX (Oxazole, 4-(1,1-dimethylethyl)-2-[2-(diphenylphosphino)phenyl]-4,5-dihydro- (4S)-)

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Catalytic enantioselective approach to the eudesmane sesquiterpenoids: total synthesis of (+)-carissone

A catalytic enantioselective approach to the eudesmane sesquiterpenoids is reported. The strategic use of a palladium-catalyzed enantioselective alkylation of vinylogous ester substrates forged the C(10) all-carbon quaternary center. This key transformation enabled a diastereoselective olefin hydrogenation to create the syn stereochemistry at C(7). The devised synthetic strategy allowed for the preparation of the antibacterial agent (+)-carissone and a formal synthesis of the P/Q-type calcium channel blocker (-)-α-eudesmol

Ring-Contraction Strategy for the Practical, Scalable, Catalytic Asymmetric Synthesis of Versatile γ-Quaternary Acylcyclopentenes

Contraction action! A simple protocol for the catalytic asymmetric synthesis of highly functionalized γ-quaternary acylcyclopentenes (see schematic) in up to 91 % overall yield and 92 % ee has been developed. The reaction sequence employs a palladium-catalyzed enantioselective alkylation reaction and exploits the unusual stability of β-hydroxy cycloheptanones to achieve a general and robust method for performing two-carbon ring contractions

Access to Functionalized Quaternary Stereocenters via the Copper-Catalyzed Conjugate Addition of Monoorganozinc Bromide Reagents Enabled by N,N-Dimethylacetamide

Monoorganozinc reagents, readily obtained from alkyl bromides, display excellent reactivity with β,β-disubstituted enones and TMSCl in the presence of Cu(I) and Cu(II) salts to synthesize a variety of cyclic functionalized β-quaternary ketones in 38–99% yields and 9:1–20:1 diastereoselectivities. The conjugate addition features a pronounced improvement in DMA using monoorganozinc bromide reagents. A simple one-pot protocol that harnesses in situ generated monoorganozinc reagents delivers comparable product yields

Determining Sequential Micellization Steps of Bile Salts With Multi-cmc Modeling

Hypothesis Bile salts exhibit complex concentration-dependent micellization in aqueous solution, rooted in a long-standing hypothesis of increasing size in bile aggregation that has historically focused on the measurement of only one CMC detected by a given method, without resolving successive stepwise aggregates. Whether bile aggregation is continuous or discrete, at what concentration does the first aggregate form, and how many aggregation steps occur, all remain as open questions. Experiments Bile salt critical micelle concentrations (CMCs) were investigated with NMR chemical shift titrations and a multi-CMC phase separation modeling approach developed herein. The proposed strategy is to establish a correspondence of the phase separation and mass action models to treat the first CMC; subsequent micellization steps, involving larger micelles, are then treated as phase separation events. Findings The NMR data and the proposed multi-CMC model reveal and resolve multiple closely spaced sequential preliminary, primary, and secondary discrete CMCs in dihydroxy and trihydroxy bile salt systems in basic (pH 12) solutions with a single model of one NMR data set. Complex NMR data are closely explained by the model. Four CMCs are established in deoxycholate below 100 mM (298 K, pH 12): 3.8 ± 0.5 mM, 9.1 ± 0.3 mM, 27 ± 2 mM, and 57 ± 4 mM, while three CMCs were observed in multiple bile systems, also under basic conditions. Global fitting leverages the sensitivity of different protons to different aggregation stages. In resolving these closely spaced CMCs, the method also obtains chemical shifts of these spectroscopically inaccessible (aka dark) states of the distinct micelles

Palladium-catalyzed asymmetric alkylation in the synthesis of cyclopentanoid and cycloheptanoid core structures bearing all-carbon quaternary stereocenters

General catalytic asymmetric routes toward cyclopentanoid and cycloheptanoid core structures embedded in numerous natural products have been developed. The central stereoselective transformation in our divergent strategies is the enantioselective decarboxylative alkylation of seven-membered β-ketoesters to form α-quaternary vinylogous esters. Recognition of the unusual reactivity of β-hydroxyketones resulting from the addition of hydride or organometallic reagents enabled divergent access to y-quaternary acylcyclopentenes through a ring contraction pathway or y-quaternary cycloheptenones through a carbonyl transposition pathway. Synthetic applications of these compounds were explored through the preparation of mono-, bi-, and tricyclic derivatives that can serve as valuable intermediates for the total synthesis of complex natural products. This work complements our previous work with cyclohexanoid systems

Access to Functionalized Quaternary Stereocenters via the Copper-Catalyzed Conjugate Addition of Monoorganozinc Bromide Reagents Enabled by N,N-Dimethylacetamide

Monoorganozinc reagents, readily obtained from alkyl bromides, display excellent reactivity with β,β-disubstituted enones and TMSCl in the presence of Cu(I) and Cu(II) salts to synthesize a variety of cyclic functionalized β-quaternary ketones in 38–99% yields and 9:1–20:1 diastereoselectivities. The conjugate addition features a pronounced improvement in DMA using monoorganozinc bromide reagents. A simple one-pot protocol that harnesses in situ generated monoorganozinc reagents delivers comparable product yields

Goal-directed and habitual control in the basal ganglia: implications for Parkinson's disease

Progressive loss of the ascending dopaminergic projection in the basal ganglia is a fundamental pathological feature of Parkinson's disease. Studies in animals and humans have identified spatially segregated functional territories in the basal ganglia for the control of goal-directed and habitual actions. In patients with Parkinson's disease the loss of dopamine is predominantly in the posterior putamen, a region of the basal ganglia associated with the control of habitual behaviour. These patients may therefore be forced into a progressive reliance on the goal-directed mode of action control that is mediated by comparatively preserved processing in the rostromedial striatum. Thus, many of their behavioural difficulties may reflect a loss of normal automatic control owing to distorting output signals from habitual control circuits, which impede the expression of goal-directed action. © 2010 Macmillan Publishers Limited. All rights reserved