General aspects of organocatalytic cyclizations

Ring-forming reactions are an essential part of synthetic chemistry and allow access to a range of useful natural products and biologically important molecules. The applications of organocatalysis to the synthesis of functionalized, enantiopure structures really begins where organocatalysis itself begins; with the Hajos-Parrish reaction in the 1970s for the synthesis of steroids using proline. This chapter then will review the uses of organocatalysts in cyclization methodology – from the initial Hajos-Parrish discovery to current advances in the field.

Organocatalytic enantioselective construction of nitrocyclohexanes containing multiple chiral centres via a cascade reaction

The stereoselective construction of complex molecules with multiple stereogenicity in a single step represents an extremely useful, but challenging approach to complexity in chemical synthesis. The development of organocatalytic cascade processes has proven useful in these studies, but reports where four or more stereocentres are created in a single step from just two achiral reagents are rare. Herein we report the development of a novel asymmetric domino Michael-Michael reaction between nitrohex-4-enoates and nitro-olefins to generate cyclohexanes of high complexity, including one with a quaternary centre, and one with five contiguous stereocentres. This methodology provides access to a range of useful nitrocyclohexane derivatives, including a novel class of a-lycorane-like structures.

Effects of omega-3 fatty acids on immune function in broiler chickens

There is interest in the enrichment of poultry meat with long-chain n-3 polyunsaturated fatty acids in order to increase the consumption of these fatty acids by humans. However, there is concern that high levels of n-3 polyunsaturated fatty acids may have detrimental effects on immune function in chickens. The effect of feeding increasing levels of fish oil (FO) on immune function was investigated in broiler chickens. Three-week-old broilers were fed 1 of 4 wheat-soybean basal diets that contained 0, 30, 50, or 60 g/kg of FO until slaughter. At slaughter, samples of blood, bursa of Fabricius, spleen, and thymus were collected from each bird. A range of immune parameters, including immune tissue weight, immuno-phenotyping, phagocytosis, and cell proliferation, were assessed. The pattern of fatty acid incorporation reflected the fatty acid composition of the diet. The FO did not affect the weight of the spleen, but it did increase thymus weight when fed at 50 g/kg (P < 0.001). Fish oil also lowered bursal weights when fed at 50 or 60 g/kg (P < 0.001). There was no significant effect of FO on immune cell phenotypes in the spleen, thymus, bursa, or blood. Feeding 60 g/kg of FO significantly decreased the percentage of monocytes engaged in phagocytosis, but it increased their mean fluorescence intensity relative to that of broilers fed 50 g/kg of FO. Lymphocyte proliferation was significantly decreased after feeding broiler chickens diets rich in FO when expressed as division index or proliferation index, although there was no significant effect of FO on the percentage of divided cells. In conclusion, dietary n-3 polyunsaturated fatty acids decrease phagocytosis and lymphocyte proliferation in broiler chickens, highlighting the need for the poultry industry to consider the health status of poultry when poultry meat is being enriched with FO.

Mild and rapid method for the generation of ortho-(naphtho)-quinone methide intermediates

A new mild method has been devised for generating o-(naphtho)quinone methides via fluoride-induced desilylation of silyl derivatives of o-hydroxybenzyl(or 1-naphthylmethyl) nitrate. The reactive o-(naphtho)quinone methide intermediates were trapped by C, O, N and S nucleophiles and underwent “inverse electron-demand” hetero Diels- Alder reaction with dienophiles to give stable adducts. The method has useful potential application in natural product synthesis and drug research

AID enzymatic activity is inversely proportional to the size of cytosine C5 orbital cloud

Activation induced deaminase (AID) deaminates cytosine to uracil, which is required for a functional humoral immune system. Previous work demonstrated, that AID also deaminates 5-methylcytosine (5 mC). Recently, a novel vertebrate modification (5-hydroxymethylcytosine - 5 hmC) has been implicated in functioning in epigenetic reprogramming, yet no molecular pathway explaining the removal of 5 hmC has been identified. AID has been suggested to deaminate 5 hmC, with the 5 hmU product being repaired by base excision repair pathways back to cytosine. Here we demonstrate that AID’s enzymatic activity is inversely proportional to the electron cloud size of C5-cytosine - H . F . methyl .. hydroxymethyl. This makes AID an unlikely candidate to be part of 5 hmC removal.

Support for global climate reorganization during the "Medieval Climate Anomaly"

Widely distributed proxy records indicate that the Medieval Climate Anomaly (MCA; *900–1350 AD) was characterized by coherent shifts in large-scale Northern Hemisphere atmospheric circulation patterns. Although cooler sea surface temperatures in the central and eastern equatorial Pacific can explain some aspects of medieval circulation changes, they are not sufficient to account for other notable features, including widespread aridity through the Eurasian sub-tropics, stronger winter westerlies across the North Atlantic and Western Europe, and shifts in monsoon rainfall patterns across Africa and South Asia. We present results from a full-physics coupled climate model showing that a slight warming of the tropical Indian and western Pacific Oceans relative to the other tropical ocean basins can induce a broad range of the medieval circulation and climate changes indicated by proxy data, including many of those not explained by a cooler tropical Pacific alone. Important aspects of the results resemble those from previous simulations examining the climatic response to the rapid Indian Ocean warming during the late twentieth century, and to results from climate warming simulations—especially in indicating an expansion of the Northern Hemisphere Hadley circulation. Notably, the pattern of tropical Indo-Pacific sea surface temperature (SST) change responsible for producing the proxy-model similarity in our results agrees well with MCA-LIA SST differences obtained in a recent proxy-based climate field reconstruction. Though much remains unclear, our results indicate that the MCA was characterized by an enhanced zonal Indo-Pacific SST gradient with resulting changes in Northern Hemisphere tropical and extra-tropical circulation patterns and hydroclimate regimes, linkages that may explain the coherent regional climate shifts indicated by proxy records from across the planet. The findings provide new perspectives on the nature and possible causes of the MCA—a remarkable, yet incompletely understood episode of Late Holocene climatic change.

Screening for Bacillus isolates in the broiler gastrointestinal tract

Spores from a number of different Bacillus species are currently being used as human and animal probiotics, although their mechanisms of action remain poorly understood. Here we describe the isolation of 237 presumptive gut-associated Bacillus spp. isolates that were obtained by heat and ethanol treatment of fecal material from organically reared broilers followed by aerobic plating. Thirty-one representative isolates were characterized according to their morphological, physiological, and biochemical properties as well as partial 16S rRNA gene sequences and screening for the presence of plasmid DNA. The Bacillus species identified included B. subtilis, B. pumilus, B. licheniformis, B. clausii, B. megaterium, B. firmus, and species of the B. cereus group, whereas a number of our isolates could not be classified. Intrinsic properties of potential importance for survival in the gut that could be advantageous for spore-forming probiotics were further investigated for seven isolates belonging to five different species. All isolates sporulated efficiently in the laboratory, and the resulting spores were tolerant to simulated gastrointestinal tract conditions. They also exhibited antimicrobial activity against a broad spectrum of bacteria, including food spoilage and pathogenic organisms such as Bacillus spp., Clostridium perfringens, Staphylococcus aureus, and Listeria monocytogenes. Importantly, the isolates were susceptible to most of the antibiotics tested, arguing that they would not act as donors for resistance determinants if introduced in the form of probiotic preparations. Together, our results suggest that some of the sporeformers isolated in this study have the potential to persist in or transiently associate with the complex gut ecosystem.

Evidence for global climate reorganization during medieval times

A synthesis of global climate model results and inferences from proxy records suggests an increased sea surface temperature gradient between the tropical Indian and Pacific Oceans during medieval times.

Probability of survival in a random exchange economy with dependent agents

In this paper I analyze the general equilibrium in a random Walrasian economy. Dependence among agents is introduced in the form of dependency neighborhoods. Under the uncertainty, an agent may fail to survive due to a meager endowment in a particular state (direct effect), as well as due to unfavorable equilibrium price system at which the value of the endowment falls short of the minimum needed for survival (indirect terms-of-trade effect). To illustrate the main result I compute the stochastic limit of equilibrium price and probability of survival of an agent in a large Cobb-Douglas economy.

The structure of the optimal income tax in the quasi-linear model

Existing numerical characterizations of the optimal income tax have been based on a limited number of model specifications. As a result, they do not reveal which properties are general. We determine the optimal tax in the quasi-linear model under weaker assumptions than have previously been used; in particular, we remove the assumption of a lower bound on the utility of zero consumption and the need to permit negative labor incomes. A Monte Carlo analysis is then conducted in which economies are selected at random and the optimal tax function constructed. The results show that in a significant proportion of economies the marginal tax rate rises at low skills and falls at high. The average tax rate is equally likely to rise or fall with skill at low skill levels, rises in the majority of cases in the centre of the skill range, and falls at high skills. These results are consistent across all the specifications we test. We then extend the analysis to show that these results also hold for Cobb-Douglas utility.

Organocatalytic domino reaction of cyanosulfones: access to complex cyclohexane systems with quaternary carbon centers

When ε-nitro-a,β-unsaturated esters are added to conjugated cyanosulfones in the presence of a bifunctional thiourea catalyst, a highly stereoselective domino reaction occurs to generate complex cyclohexanes with up to four stereogenic centers, one of which is quaternary in nature. Therefore, it is demonstrated that, like nitro compounds, sulfones can undergo an asymmetric intramolecular conjugate addition to r,β- unsaturated esters in the presence of a bifunctional organocatalyst.

Asymmetric organocatalysis and the nitro group functionality

The nitro group is an exceptionally versatile functional group, not only because it is essentially a masked amine, but also because its chemistry can be exploited in a number of useful ways. Asymmetric organocatalysis in particular has capitalized on the use of the nitro group towards the synthesis of a variety of nitrogen- containing targets. Perhaps of greatest interest is that this functional group has been shown to be invaluable within the rapidly expanding field of organocatalytic domino reactions. This review features selected examples of nitro group reactivity in organocatalysis to demonstrate its dynamism and utility.