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Cultivation of soybean and off-season corn is advancing in areas under restricted edaphoclimatic conditions, such as petric plinthosols, which have significant proportions of gravel and are deficiency in micro-nutrients such as copper (Cu) and zinc (Zn). The effects of Cu and Zn concentrations on soybean nutrition cultivated in petric plinthosol are unclear, and it is unknown whether the levels considered adequate for other soils are sufficient for gravely soils, or even if higher Cu and Zn rates can cause a toxic effect in soybean. The objective was to compare the response of soybean grown in petric plinthosol and ferralsol to Cu and Zn doses for identifying the changes induced by gravel soils and to evaluate the residual effect on off-season corn grown in ferralsol. Four experiments were carried out with Cu and Zn doses applied to soil with the soybean crop in ferralsol and plinthosol. The leaf tissues of soybean crops in the two soils showed the same rate of increase in Zn concentrations, for each kg·ha-1 of Zn applied, the increase in Zn was 0.7 mg·kg-1, suggesting no difference in the effect of Zn fertilization between soils with and without gravel. The dosages of Zn and Cu Oxysulfate applied to soil did not cause residual effects in the off-season corn. The highest doses of Cu and Zn did not have any toxic effects on the plants. The main criteria for interpreting Cu and Zn in soil analysis are thus also applicable to soybean crops grown in petric plinthosol. RESUMO - O cultivo de soja e milho safrinha avança em condições edafoclimáticas restritivas, como nos Plintossolos Pétricos, que apresentam proporções consideráveis de cascalho no seu perfil e são deficientes em cobre (Cu) e zinco (Zn). Não se sabe os efeitos de doses de Cu e Zn na nutrição da soja cultivada em Plintossolo Pétrico, nem se os níveis considerados adequados para outros solos são suficientes para solos cascalhentos, ou ainda, se altas doses de Cu e Zn podem causar toxidez nas plantas de soja. O objetivo foi comparar a resposta a doses de Cu e Zn em soja cultivada em Plintossolo Pétrico e em Latossolo, a fim de identificar alterações provocadas pelo solo com cascalho, e adicionalmente, avaliar o efeito residual da adubação feita na soja para o milho safrinha cultivado no Latossolo. Quatro experimentos foram desenvolvidos com doses de Cu e Zn aplicadas via solo na cultura da soja em Latossolo e em Plintossolo Pétrico. Houve a mesma taxa de incremento na concentração de Zn no tecido foliar da soja nos dois solos estudados, para cada kg ha-1 de Zn aplicado, o incremento foi de 0,7 mg·kg-1 demonstrando que não há diferença de um solo com ou sem cascalho para os efeitos da adubação. As doses de oxissulfato de Zn e Cu aplicadas via solo não causaram efeito residual no milho safrinha. As maiores doses de Cu e Zn não causaram efeito tóxico nas plantas. Os principais critérios de interpretação de Cu e Zn em análise do solo se aplicam para soja cultivada em Plintossolo Pétrico. Made available in DSpace on 2022-08-28T04:00:47Z (GMT). No. of bitstreams: 1 cr-2023.pdf: 720778 bytes, checksum: f594d3ad3f1c6b51a9c9af019caae6e3 (MD5) Previous issue date: 2023

5-Lipoxygenase activating protein (FLAP) inhibitors attenuate 5-lipoxygenase pathway activity and reduce the production of proinflammatory and vasoactive leukotrienes. As such, they are hypothesized to have therapeutic benefit for the treatment of diseases that involve chronic inflammation including coronary artery disease. Herein, we disclose the medicinal chemistry discovery and the early clinical development of the FLAP inhibitor AZD5718 (12). Multiparameter optimization included securing adequate potency in human whole blood, navigation away from Ames mutagenic amine fragments while balancing metabolic stability and PK properties allowing for clinically relevant exposures after oral dosing. The superior safety profile of AZD5718 compared to earlier frontrunner compounds allowed us to perform a phase 1 clinical study in which AZD5718 demonstrated a dose dependent and greater than 90% suppression of leukotriene production over 24 h. Currently, AZD5718 is evaluated in a phase 2a study for treatment of coronary artery disease.

Problematic smartphone usage, associated with impaired daily functioning, has gained increased attention among researchers. However, extant research is focusing on adolescents and younger adults. This paper investigates smartphone usage among older adults, of which less is known. To do so, we conducted a cross-sectional survey of 154 smartphone users (60+ years) in Norway using structural equation modeling (PLS-SEM). We examined the contributing roles of loneliness, habit, social influence, emotional gain, fear of missing out, self-control, and problematic smartphone usage. We further investigated how older adults engage with their smartphones. Our findings suggest that older adults use smartphones for various social and non-social reasons and that social media and news reading are the most common use areas. Furthermore, we found a low prevalence of problematic smartphone usage among older adults. Whereas social influence and habit were strong predictors of smartphone usage among older adults, loneliness was not. Fear of missing out was not prevalent among older adults. As we expected, higher self-control was associated with lower problematic smartphone use. Finally, we discuss the contributions and implications of our findings.

Electric power generation in Albania has been almost totally dependent on hydropower since the system inception. In the last decade, although modest, there has been an increased share of power produced from Renewable Energy Sources (RES), mostly from Solar Power Plants. Looking forward, the Albanian government has considered the promotion of Renewable Energy as an important part of energy policies. Some of the future targets are to increase more the share of injected Renewable Energy in terms of hydro, Photovoltaic (PV) and Wind. Wind Energy is one of the most discussed sources regarding renewable energy penetration. Starting from feasibility studies to the quality of power, there are many issues to be addressed before installations of Wind Energy can be considered. This paper gives an overview of the studies performed regarding System Frequency Response (SFR) by replacing hydro inertia with non-synchronous generation. The paper presents a study of frequency behavior under several penetration levels of non- synchronous generation. Also presented are the results of study cases which show how system frequency is affected when replacing hydro-power inertia with wind turbine converter inertia.

The integration of renewable resources is quickly growing in the Nordic power system (NPS), and it has led to increasing challenges for the operation and control of the NPS. Nordic countries require that the first-generation power plants have a more flexible operation regime to overcomes power imbalances coming from fluctuations of the demand and supply. This paper assesses optimal frequency support of variable-speed hydropower plants installed in Telemark and Vestfold, Norway, considering future scenarios of NPS. The total kinetic energy of the NPS is expected to be significantly reduced in the future. This paper looks into the implementation of hydropower units with a variable-speed operation regime and battery energy storage systems (BESS), equipped with fast-active power controller (FAPC) technology, to provide fast frequency response after a system frequency disturbance. The frequency support was formulated as an optimization process; therefore, the parameter of the FAPC was optimally calculated for future scenarios of low inertia in NPS. Three main futures scenarios were developed for technology penetration in the Vestfold and Telemark area in Norway. The simulation results showed that the integration variable-speed hydropower units and BESS technologies improved the frequency response even in low-kinetic energy scenarios.

[Image: see text] In order to assess the potential of sPLA(2)-X as a therapeutic target for atherosclerosis, novel sPLA(2) inhibitors with improved type X selectivity are required. To achieve the objective of identifying such compounds, we embarked on a lead generation effort that resulted in the identification of a novel series of indole-2-carboxamides as selective sPLA2-X inhibitors with excellent potential for further optimization.

Proprotein convertase subtilisin kexin like type 9 (PCSK9) has since its discovery been a key protein target for the modulation of LDL cholesterol. The interest in PCSK9 has grown even more with the positive clinical trial outcomes in cardiovascular disease recently reported for two PCSK9 antibodies. Currently, there are no PCSK9 small molecule programs active in clinical development. However, there has been a steady increase in publications and patent applications within the PCSK9 small molecule field. This digest will provide a summary of small molecule and peptide PCSK9 modulators reported both in scientific journals and in patent applications, most of them originating from the last 3–4 years. As such, this digest will serve as an introduction to the field and assist further identification and discovery of small molecule PCSK9 modulators.

Expedited structure-based optimization of the initial fragment hit 1 led to the design of (R)-7 (AZD2716) a novel, potent secreted phospholipase A2 (sPLA2) inhibitor with excellent preclinical pharmacokinetic properties across species, clear in vivo efficacy, and minimized safety risk. Based on accumulated profiling data, (R)-7 was selected as a clinical candidate for the treatment of coronary artery disease.

[Image: see text] A lead generation campaign identified indole-based sPLA(2)-X inhibitors with a promising selectivity profile against other sPLA(2) isoforms. Further optimization of sPLA(2) selectivity and metabolic stability resulted in the design of (−)-17, a novel, potent, and selective sPLA(2)-X inhibitor with an exquisite pharmacokinetic profile characterized by high absorption and low clearance, and low toxicological risk. Compound (−)-17 was tested in an ApoE(–/–) murine model of atherosclerosis to evaluate the effect of reversible, pharmacological sPLA(2)-X inhibition on atherosclerosis development. Despite being well tolerated and achieving adequate systemic exposure of mechanistic relevance, (−)-17 did not significantly affect circulating lipid and lipoprotein biomarkers and had no effect on coronary function or histological markers of atherosclerosis.

A class of novel oral fibrinolysis inhibitors has been discovered, which are lysine mimetics containing an isoxazolone as a carboxylic acid isostere. As evidenced by X-ray crystallography the inhibitors bind to the lysine binding site in plasmin thus preventing plasmin from binding to fibrin, hence blocking the protein-protein interaction. Optimization of the series, focusing on potency in human buffer and plasma clotlysis assays, permeability, and GABAa selectivity, led to the discovery of AZD6564 (19) displaying an in vitro human plasma clot lysis IC50 of 0.44 μM, no detectable activity against GABAa, and with DMPK properties leading to a predicted dose of 340 mg twice a day oral dosing in humans.

Expedited structure-based optimization of the initial fragment hit

The amendment of phosphorus shortage is indispensable to elevate the capacity of animal support capacity of a pasture. To improve P status of these soils and to know the qualitative and quantitative effect of phosphorus fertilizer on the forage Tanzânia-1, an experiment was conducted in one dark red latosol , at Santo Antônio de Goiás - GO. The soil was prepared by using a harrow and one ploughing, and sowing was done after a week. The plots were fertilized by using 0; 50 and 100 kg of P ha-1 of commercial thermo-phosphate in previously amended soil with 3 t ha-1 of dolomite lime. The mean values of plant height, budding, green mass and dry matter increased but decreased the gross protein and increased the fiber contents. The phosphorus fertilizer didn’t influence potassium, calcium, zinc and manganese contents in the leaf tissue of plants. However, it reduced phosphorus, copper and iron contents but increased the magnesium contents. KEY-WORDS: Savanah; mineral nutricion; Panicum maximum; pasture. Para a correção das carências de fósforo do solo, e considerada imprescindível para elevar a capacidade de suporte animal de uma pastagem, para conhecimento do efeito qualitativo e quantitativo do fósforo na forrageira Tanzânia-1, foi realizado um experimento em um latossolo vermelho-escuro, em Santo Antônio de Goiás, no Estado de Goiás. Para isso, preparou-se o solo com uma gradagem e uma aração e, após uma semana, realizou-se a semeadura. Os tratamentos incluíram 0,50 e 100 kg de P ha-1 de termofosfato comercial, em cobertura, em terreno previamente corrigido com 3 t ha-1 calcário dolomítico. Com o incremento de fósforo, houve um aumento dos valores médios de altura das plantas, número de perfilhos, massa verde e matéria seca, mas uma diminuição dos teores de proteína bruta, como também um aumento das concentrações de fibra. O fósforo não interferiu nos teores de potássio, cálcio, zinco e manganês no tecido foliar das plantas, contudo reduziu os teores de fósforo, cobre e ferro e aumentou os teores de magnésio. PALAVRAS-CHAVE: Cerrado; nutrição animal; Panicum maximum; pastagem.

Para a correção das carências de fósforo do solo, e considerada imprescindível para elevar a capacidade de suporte animal de uma pastagem, para conhecimento do efeito qualitativo e quantitativo do fósforo na forrageira Tanzânia-1, foi realizado um experimento em um latossolo vermelho-escuro, em Santo Antônio de Goiás, no Estado de Goiás. Para isso, preparou-se o solo com uma gradagem e uma aração e, após uma semana, realizou-se a semeadura. Os tratamentos incluíram 0,50 e 100 kg de P ha-1 de termofosfato comercial, em cobertura, em terreno previamente corrigido com 3 t ha-1 calcário dolomítico. Com o incremento de fósforo, houve um aumento dos valores médios de altura das plantas, número de perfilhos, massa verde e matéria seca, mas uma diminuição dos teores de proteína bruta, como também um aumento das concentrações de fibra. O fósforo não interferiu nos teores de potássio, cálcio, zinco e manganês no tecido foliar das plantas, contudo reduziu os teores de fósforo, cobre e ferro e aumentou os teores de magnésio. PALAVRAS-CHAVE: Cerrado; nutrição animal; Panicum maximum; pastagem. The amendment of phosphorus shortage is indispensable to elevate the capacity of animal support capacity of a pasture. To improve P status of these soils and to know the qualitative and quantitative effect of phosphorus fertilizer on the forage Tanzânia-1, an experiment was conducted in one dark red latosol , at Santo Antônio de Goiás - GO. The soil was prepared by using a harrow and one ploughing, and sowing was done after a week. The plots were fertilized by using 0; 50 and 100 kg of P ha-1 of commercial thermo-phosphate in previously amended soil with 3 t ha-1 of dolomite lime. The mean values of plant height, budding, green mass and dry matter increased but decreased the gross protein and increased the fiber contents. The phosphorus fertilizer didn’t influence potassium, calcium, zinc and manganese contents in the leaf tissue of plants. However, it reduced phosphorus, copper and iron contents but increased the magnesium contents. KEY-WORDS: Savanah; mineral nutricion; Panicum maximum; pasture.

A number of FLAP inhibitors have been progressed to clinical trials for respiratory and other inflammatory indications but so far no drug has reached the market. With this Digest we assess the opportunity to develop FLAP inhibitors for indications beyond respiratory disease, and in particular for atherosclerotic cardiovascular disease. We also show how recently disclosed FLAP inhibitors have structurally evolved from the first generation FLAP inhibitors paving the way for new compound classes.

A number of FLAP inhibitors have been progressed to clinical trials for respiratory and other inflammatory indications but so far no drug has reached the market. With this Digest we assess the opportunity to develop FLAP inhibitors for indications beyond respiratory disease, and in particular for atherosclerotic cardiovascular disease. We also show how recently disclosed FLAP inhibitors have structurally evolved from the first generation FLAP inhibitors paving the way for new compound classes.

A simple and efficient organocatalytic enantioselective hydrophosphonylation of imines to enantiomerically enriched alpha-amino phosphonates is reported. By using 10 mol % of quinine as the catalyst in the enantioselective addition of diethyl phosphite to N-Boc protected imines, alpha-amino phosphonates are obtained in moderate to good yields and with up to 94% ee.

Investigation of site selectivity of the stereoselective deprotonation of cyclohexene oxide using kinetic resolution of isotopic enantiomers in natural abundance

The efficient synthesis of enantiomerically pure (S)-1,7-diaza[4.6]undecane and (S)-7-methyl-1,7-diaza[4.6]undecane and related compounds is reported. These novel diamines are obtained from (S)-proline, which is reacted with chloral to give an enantiomerically pure oxazolidinone, which is alkylated at the α-position using cis-1,4-dibromobutene. The resulting allylbromide is then reacted with ammonia or methylamine to yield, as intermediates, allylamines, which ring close to give the corresponding spirolactams. The parent and the 7-methyl (S)-5.7-spirodiamines are obtained via reduction in two steps of the spirolactams. The expected absolute configuration was confirmed by X-ray structural analysis. Enantiomeric excess (>99.8% ee) was determined using the Mosher amides of the spirodiamines and gas chromatography.

Stereoselective deprotonation of cyclohexene oxide, using a mixed dimer built of the chiral lithium amide, lithium (1R,2S)-N-methyl-1-phenyl-2-pyrrolidinyl-propanamide, and 2-lithio-1-methylimidazole, has been studied. The composition of the rate limiting activated complex was determined by kinetics to be built from one mixed dimer molecule and one epoxide molecule. Based on this knowledge computational chemistry has been applied to gain insight into possible structures of the activated complexes.

Novel bulk bases have been developed yielding improved enantioselectivity of chiral lithium amide catalysed deprotonations as compared to using the bulk base lithium diisopropylamide (LDA). The new bulk bases are 2-lithio-1-methylimidazole, 2-(lithiomethyl)-1-methylimidazole, 2-lithio-furan and 1,8-diazabicyclo-6-lithio[5.4.0]undec-7-ene which have been used together with chiral lithium amides in deprotonations of cyclohexene oxide. Using the chiral lithium amides enhanced stereoselectivities (96% ee) have been reached. The reactivity change has been traced to the formation of novel reagents—mixed dimers—formed from a bulk base molecule and a molecule of a chiral lithium amide. The results also show that DBU, which has commonly been used as an additive to alter reactivity and enantioselectivity in deprotonations, has another important role. DBU is lithiated under the conditions used and becomes a bulk base, which forms catalytic mixed dimers with the chiral lithium amides.

The search for non-reactive bulk bases in replacement of lithium diisopropylamide (LDA) for improved enantioselectivity of chiral lithium amide-catalysed deprotonations led to the use of 1,2-dimethylimidazole 9 as a precursor. Deprotonation of 9 with n-BuLi in THF results in the compound 2-(lithiomethyl)-1-methylimidazole 8 as shown by NMR. This carbanionic compound is found to be less reactive than LDA in deprotonation of cyclohexene oxide 10, but having comparable basicity to that of LDA. Catalytic amounts of the chiral lithium amide 4 of (1R,2S)-N-methyl-1-phenyl-2-pyrrolidinopropanamine 5 deprotonates cyclohexene oxide 10 in the presence of compound 8 and yields (S)-cyclohex-2-enol (S)-11 in 93% ee. On the other hand, using LDA as a bulk base gives an ee of only 22%. Interestingly, stoichiometric deprotonation by 4 in the presence of 8 in THF results in (S)-11 in 96% ee. Thus, the results indicate that compound 8 is playing a more intimate role in the deprotonation than just acting as a bulk base. Therefore, the reagents involved in the reactions have been investigated by 1H, 6Li and 13C NMR using isotopically labelled compounds. The results show that lithium amide 4, which is homodimeric in THF, in the presence of 8 forms heterodimer 12 composed of one monomer of carbanionic 8 and one monomer of 4. This novel heterodimer is found to be the deprotonating reagent causing the increased enantioselectivity. It is concluded that lithium amide 4 is not basic enough to deprotonate 9, but that 8 is a strong enough base to deprotonate diamine 5. This contrasts with the behaviour of 1-methylimidazole 1 which was found to be deprotonated by 4 to yield the mixed dimer 3. Computational investigations using PM3 and B3LYP/6-31+G(d) show possible structures of the heterodimer 12 and homodimer 14 of 8, and the role of THF and 9 in the solvation of the dimers. Favoured complexes in the equilibria between homo- and heterocomplexes are reported. It is concluded that 9 will completely replace THF in the solvation of the dimers even at low concentrations of 9.

Improved stereoselectivity has been obtained by using 2-lithium-1-methylimidazole, 2, as a replacement for lithium diisopropylamide (LDA) as a bulk base in catalytic deprotonations. The chiral lithium amide 6 of (1R,2S)-N-methyl-1-phenyl-2-pyrrolidinylpropanamine, 5, has been found to deprotonate cyclohexene oxide 3 in the presence of compound 2 to yield (S)-cyclohex-2-en-1-ol, 4, in 96% ee. Compound 2 is a carbenoid species conveniently generated from nBuLi and 1-methylimidazole, 1. The base 2 has also been found to play a more intimate role in the deprotonation. Investigations by 1H, 6Li and 13C NMR of the 6Li/15N isotopologue 8 of 6 have shown that 6 is homodimeric in THF and that, in the presence of 2, it forms a novel heterodimer 10. This heterodimer is found to be the dominant reagent in the initial state, rather than the homodimer of 6. Computational investigations with PM3 and B3LYP/6-311 + G(d,p) have shown possible structures of the heterodimers, as well as the role of THF and I in the solvation of the dimers. The results are in line with the NMR results. Favoured complexes in the equilibria between homo- and heterocomplexes are also reported.

Rational design of efficient chiral lithium amides for enantioselective deprotonations demands understanding of the origin of the selectivity. The mechanism of deprotonation of cyclohexene oxide 1 by lithium (1R,2S)-N-methyl-1-phenyl-2-pyrrolidinylpropanamide 3, which yields (S)-cyclohex-2-en-1-ol (S)-5 in 93% enantiomeric excess in tetrahydrofuran (THF), has been investigated. Kinetics have been used to show that the reaction is first order with respect to the reagents 1 and 3, respectively. NMR investigations of a 6Li and 15N labelled isotopologue of 3 have previously shown that 3 is mainly a dimer of the lithium amide monomer in THF in the initial state. On the basis of these results it is concluded that the rate-limiting activated complexes for the epoxide deprotonation are composed of two molecules of monomer of lithium amide 3 and one molecule of epoxide. Structures and energies of unsolvated and specific THF-solvated reagents and activated complexes have been calculated using PM3 and B3LYP/6-31+G(d). The results are currently being explored for the rational design of chiral lithium amides with improved stereoselectivities.

The search for non-reactive bulk bases in replacement of lithium diisopropylamide (LDA) for improved enantioselectivity of chiral lithium amide-catalysed deprotonations led to the use of 1,2-dimethylimidazole 9 as a precursor. Deprotonation of 9 with n-BuLi in THF results in the compound 2-(lithiomethyl)-1-methylimidazole 8 as shown by NMR. This carbanionic compound is found to be less reactive than LDA in deprotonation of cyclohexene oxide 10, but having comparable basicity to that of LDA. Catalytic amounts of the chiral lithium amide 4 of (1R,2S)-N-methyl-1-phenyl-2-pyrrolidinopropanamine 5 deprotonates cyclohexene oxide 10 in the presence of compound 8 and yields (S)-cyclohex-2-enol (S)-11 in 93% ee. On the other hand, using LDA as a bulk base gives an ee of only 22%. Interestingly, stoichiometric deprotonation by 4 in the presence of 8 in THF results in (S)-11 in 96% ee. Thus, the results indicate that compound 8 is playing a more intimate role in the deprotonation than just acting as a bulk base. Therefore, the reagents involved in the reactions have been investigated by 1H, 6Li and 13C NMR using isotopically labelled compounds. The results show that lithium amide 4, which is homodimeric in THF, in the presence of 8 forms heterodimer 12 composed of one monomer of carbanionic 8 and one monomer of 4. This novel heterodimer is found to be the deprotonating reagent causing the increased enantioselectivity. It is concluded that lithium amide 4 is not basic enough to deprotonate 9, but that 8 is a strong enough base to deprotonate diamine 5. This contrasts with the behaviour of 1-methylimidazole 1 which was found to be deprotonated by 4 to yield the mixed dimer 3. Computational investigations using PM3 and B3LYP/6-31+G(d) show possible structures of the heterodimer 12 and homodimer 14 of 8, and the role of THF and 9 in the solvation of the dimers. Favoured complexes in the equilibria between homo- and heterocomplexes are reported. It is concluded that 9 will completely replace THF in the solvation of the dimers even at low concentrations of 9.

The unprecedented use of phase-transfer catalysis (PTC) in an asymmetric hydrophosphonylation reaction allows the obtainment of a range of optically active α-amino phosphonic acid derivatives directly from α-amido sulfones.

The unprecedented use of phase-transfer catalysis (PTC) in an asymmetric hydrophosphonylation reaction allows the obtainment of a range of optically active alpha-amino phosphonic acid derivatives directly from alpha-amido sulfones.

A novel organocatalytic approach for aza-Michael reaction of chalcones using commercial and non-expensive O-benzylhydroxylamine and a readily available organocatalyst is provided. The use of this simple protocol results in β-keto hydroxylamines in up to 60% ee, thus extending the generality of the catalytic enantioselective aza-Michael reaction.

Different malonates and beta-ketoesters can react with N-tert-butoxycarbonyl- (N-Boc) and N-benzyloxycarbonyl- (N-Cbz) protected alpha-amido sulfones in an organocatalytic asymmetric Mannich-type reaction. The reaction makes use of a simple and easily obtained phase-transfer catalyst and proceeds under very mild and user-friendly conditions. The optimised protocol avoids the preparation and the isolation of the relatively unstable N-Boc and N-Cbz imines that are generated in situ from the bench-stable alpha-amido sulfones. The corresponding Mannich bases are generally obtained in good yields and enantioselectivities, and can be readily transformed into key compounds, such as optically active beta3-amino acids in one easy step. Enantioenriched N-Boc and N-Cbz protected beta-amino acids that are suitable for peptide synthesis are also available from the Mannich adducts through simple manipulations. Control experiments showed the dual role of the enolate-catalyst ion pair in this reaction, as well as the crucial role of the presence of water to achieve high enantioselectivities.

Different malonates and beta-ketoesters can react with N-tert-butoxycarbonyl- (N-Boc) and N-benzyloxycarbonyl- (N-Cbz) protected alpha-amido sulfones in an organocatalytic asymmetric Mannich-type reaction. The reaction makes use of a simple and easily obtained phase-transfer catalyst and proceeds under very mild and user-friendly conditions. The optimised protocol avoids the preparation and the isolation of the relatively unstable N-Boc and N-Cbz imines that are generated in situ from the bench-stable alpha-amido sulfones. The corresponding Mannich bases are generally obtained in good yields and enantioselectivities, and can be readily transformed into key compounds, such as optically active beta3-amino acids in one easy step. Enantioenriched N-Boc and N-Cbz protected beta-amino acids that are suitable for peptide synthesis are also available from the Mannich adducts through simple manipulations. Control experiments showed the dual role of the enolate-catalyst ion pair in this reaction, as well as the crucial role of the presence of water to achieve high enantioselectivities.

A novel organocatalytic approach for aza-Michael reaction of chalcones using commercial and non-expensive O-benzylhydroxylamine and a readily available organocatalyst is provided. The use of this simple protocol results in β-keto hydroxylamines in up to 60% ee, thus extending the generality of the catalytic enantioselective aza-Michael reaction.

We describe a biomimetic organocatalytic enantioselective decarboxylative addition of malonic acid half thioesters to imines. This simple protocol makes use of readily available Cinchona-derived organocatalysts and nucleophiles at the carboxylate oxidation state. The resulting β-amino thioesters, being attractive precursors for the preparation of optically active β-amino acids, are formed in good yields and in up to 79 % ee. As suggested by several mechanistic insights the desired products are formed via initial formation of a thioester acetate enolate via decarboxylation of the malonic acid half thioester, followed by addition to the imine.