Rational design of a (S)-selective-Transaminase for asymmetric synthesis of (1S)-1-(1,1'-biphenyl 2-yl)ethanamine

Amine transaminases offer an environmentally sustainable synthesis route for the production ofpure chiral amines. However, their catalytic efficiency towards bulky ketone substrates isgreatly limited by steric hindrance and therefore presents a great challenge for industrialsynthetic applications. Hereby we report an example of rational transaminase enzyme design tohelp alleviate these challenges. Starting from the Vibrio fluvialis amine transaminase that has nodetectable catalytic activity towards the bulky aromatic ketone 2-acetylbiphenyl, we employed arational design strategy combining in silico and in vitro studies to engineer the transaminaseenzyme with a minimal number of mutations, achieving an high catalytic activity and highenantioselectivity. We found that by introducing two mutations W57G/R415A detectableenzyme activity was achieved. The rationally designed best variant,W57F/R88H/V153S/K163F/I259M/R415A/V422A, showed an improvement in reaction rateby > 1716-fold towards the bulky ketone under study, producing the corresponding enantiomericpure (S)-amine (ee value of > 99%). 

Studies on the Catalytic Asymmetric Fischer Indolization

This work describes further developments and applications of the catalytic asymmetric Fischer indolization. In the first part of this thesis, the development of an organocatalytic asymmetric synthesis of helicenes via a Fischer indolization is discussed. The application of a novel SPINOL-derived phosphoric acid, featuring extended π-surfaces as 3,3‘-substituents which can potentially participate in π-interactions with the polyaromatic intermediate, afforded the corresponding products in high yields and enantioselectivities. The second part of this work describes the development of a catalytic asymmetric dearomatizing synthesis of 1,4-diketones via an interrupted Fischer indolization. Employing aryl hydrazines with α-substituents next to the hydrazine group prevents the rearomatization which takes place in common Fischer indole syntheses, thus enabling the hydrolysis of the generated diimine species. In the presence of STRIP as catalyst, a variety of different 1,4-diketones could be obtained in generally high yields, diastereo- and enantioselectivities. The last part of this thesis deals with the development of an organocatalytic asymmetric stereodivergent synthesis of novel 3H- and 2H-pyrroles, applying an interrupted Fischer indolization and for the 2H-pyrroles a subsequent stereospecific [1,5]-alkyl shift. Employing STRIP as catalyst afforded the corresponding products in good to excellent yields and enantioselectivities. Preliminary biological investigations of these novel structure motifs in cell-based assays, monitoring biological signal transduction pathways showed an inhibition of the Hedgehog signaling pathway in a μM range.

Asymmetric polygons with maximum area

We say that a polygon inscribed in the circle is asymmetric if it contains no two antipodal points being the endpoints of a diameter. Given n diameters of a circle and a positive integer k < n, this paper addresses the problem of computing a maximum area asymmetric k-gon having as vertices k < n endpoints of the given diameters. The study of this type of polygons is motivated by ethnomusiciological applications.

Rhodium-catalysed enantioselective C-H functionalization in asymmetric synthesis

Catalytic asymmetric synthesis of alfa,alfa-disubstituted alfa-thio- and alfa-amino acid derivatives

449 p.

Effects of an asymmetric friction on the nonlinear equilibration of a baroclinic system

Following some recent linear and nonlinear studies the authors examine, using numerical simulations of a classical two-layer model, the effect of an asymmetric friction on the nonlinear equilibrium of moderately unstable baroclinic systems, The results show that the presence of an asymmetric friction leads to a significant wave scale selection: ''long'' waves (in terms of their zonal wavelengths) emerge with a traditional asymmetric friction (with the upper layer less viscous than the lower layer), while only ''short'' waves dominate with a nontraditional asymmetric friction (with the lower layer less viscous than the upper layer). The role of the nonlinear interactions and. more precisely, the effects of an asymmetric friction on the wave-mean flow and wave-wave interactions; and their consequences on the wave scale selection are examined.

Invertibility characterization of Wiener-Hopf plus Hankel operators on variable exponent Lebesgue spaces via even asymmetric factorization

We obtain invertibility and Fredholm criteria for the Wiener-Hopf plus Hankel operators acting between variable exponent Lebesgue spaces on the real line. Such characterizations are obtained via the so-called even asymmetric factorization which is applied to the Fourier symbols of the operators under study.

States' Responding Behavior in Conflict: Asymmetric Response and Strategic Conflict Avoidance

State responses to external threats and aggression are studied with focus on two different rationales: (1) to make credible deterrent threats to avoid being exploited, and (2) to minimize the risk of escalation to unwanted war. Given external aggression, the target state's responding behavior has three possibilities: concession (under-response), reciprocation, and escalation. This study focuses on the first two possibilities and investigates how the strategic nature of crisis interaction can explain the intentional choice of concession or avoidance of retaliation. I build a two-level bargaining model that accounts for the domestic bargaining situation between the leader and the challenger for each state. The model's equilibrium shows that the responding behavior is determined not only by inter-state level variables (e.g. balance of power between two states, or cost of war that each state is supposed to pay), but also the domestic variables of both states. Next, the strategic interaction is rationally explained by the model: as the responding state believes that the initiating state has strong domestic challenges and, hence, the aggression is believed to be initiated for domestic political purposes (a rally-around-the-flag effect), the response tends to decrease. The concession is also predicted if the target state leader has strong bargaining power against her domestic challengers \emph{and} she believes that the initiating leader suffers from weak domestic standing. To test the model's prediction, I conduct a lab experiment and case studies. The experimental result shows that under an incentivized bargaining situation, individual actors are observed to react to hostile action as the model predicts: if the opponent is believed to suffer from internally driven difficulties, the subject will not punish hostile behavior of the other player as severely as she would without such a belief. The experiment also provides supporting evidence for the choice of concession: when the player finds herself in a favorable situation while the other has disadvantages, the player is more likely to make concessions in the controlled dictator game. Two cases are examined to discuss how the model can explain the choice of either reciprocation or concession. From personal interviews and fieldwork in South Korea, I find that South Korea's reciprocating behavior during the 2010 Yeonpyeong Island incident is explained by a combination of `low domestic power of initiating leader (Kim Jong-il)' and `low domestic power of responding leader (Lee Myung-bak).' On the other hand, the case of EC-121 is understood as a non-response or concession outcome. Declassified documents show that Nixon and his key advisors interpreted the attack as a result of North Korea's domestic political instabilities (low domestic power of initiating leader) and that Nixon did not have difficulties at domestic politics during the first few months of his presidency (high domestic power of responding leader).

Alfa'-oxy enones and pyrrolidin-2,3-diones as efficient new templates in asymmetric organocatalytic Michael reactions

470 p.

Capital structure, risk and asymmetric information : theory and evidence

This paper proposes a principal-agent model between banks and firms with risk and asymmetric information. A mixed form of finance to firms is assumed. The capital structure of firms is a relevant cause for the final aggregate level of investment in the economy. In the model analyzed, there may be a separating equilibrium, which is not economically efficient, because aggregate investments fall short of the first-best level. Based on European firm-level data, an empirical model is presented which validates the result of the relevance of the capital structure of firms. The relative magnitude of equity in the capital structure makes a real difference to the profits obtained by firms in the economy.

On the reactivity of naphthalene and biphenyl dianions: tying up loose ends concerning an SN2-ET dichotomy in alkylation reactions

Naphthalene and biphenyl dianions are interesting compounds that can be obtained by double reduction of the corresponding arenes in solution with certain alkali metals. These dianions are highly reactive and rather elusive species with very high laying and highly delocalized electrons. They share many aspects of the reactivity of the alkali metal they originated from and consequently behave primarily as strong electron transfer (ET) reagents. We report here kinetic evidence for a different type of reactivity in their alkylation reactions with alkyl fluorides. By using cyclopropylmethyl fluoride (c-C3H5CH2F) as a very fast radical probe, we were able to settle that this alkylation does not involve the classical electron transfer reaction followed by radical coupling between diffusing radicals, but supports the alternative SN2 concerted mechanism, discerning thus this mechanistic SN2-ET dichotomy.

Catalytic asymmetric transfer hydrogenation of ketones: recent advances

In this review, we consider the main processes for the asymmetric transfer hydrogenation of ketones from 2008 up today. The most effective organometallic compounds (derived from Ru, Rh, Ir, Fe, Os, Ni, Co, and Re) and chiral ligands (derived from amino alcohols, diamines, sulfur- and phosphorus-containing compounds, as well as heterocyclic systems) will be shown paying special attention to functionalized substrates, tandem reactions, processes under non-conventional conditions, supported catalysts, dynamic kinetic resolutions, the use of water as a green solvent, theoretical and experimental studies on reaction mechanisms, enzymatic processes, and finally applications to the total synthesis of biologically active organic molecules.