Intramolecular [2 + 2] Cycloaddition Reactions of Allene-ynes: Exploring the Scope, Mechanism, and Application to the Synthesis of Carbocyclic Spirooxindoles

The thermal allene-yne [2 + 2] cycloaddition reaction provides quick and efficient access to alkylidene cyclobutene compounds containing a fused bicyclic ring structure. The mechanism of this reaction was examined computationally in collaboration with Dean Tantillo and Matthew Siebert and experimentally in our lab. Computational studies suggest that the allene-yne [2 + 2] cycloaddition reaction proceeds via a stepwise diradical pathway. It is commonplace for researchers to postulate diradical intermediates for thermally disallowed cycloaddition reactions, but rarely are experiments conducted to support their existence. Experimental efforts to trap the postulated diradical intermediate included appending a cyclopropane to various allene-yne substrates. In two examples, products resulting from cyclopropane ring opening were isolated and characterized, thus providing experimental evidence supporting a diradical intermediate. The scope of the thermal allene-yne [2 + 2] cycloaddition reaction was expanded to the preparation of spirocyclobutene oxindoles. Our investigation led to the discovery of a tandem thermal [3,3]-sigmatropic rearrangement/[2 + 2] cycloaddition reaction of propargyl esters to afford carbocyclic spirooxindoles. This methodology lent itself to the formation of both spirobicyclo[4.2.0]oxindoles and spirobicyclo[5.2.0]oxindoles in moderate yields. The scope of the reaction was expanded to the synthesis of potentially biologically active spirocyclobutene oxindole compounds. Transfer of chirality from an allene to the [2 + 2] cycloadduct was possible when using a tert-butyl substituted allene; however in the case of a propargyl acetate substrate, complete racemization was observed during the tandem [3,3]-sigmatropic rearrangement/[2 + 2] cycloaddition reaction. We hypothesize that the bulkiness of the tert-butyl group and oxindole restricts rotation at the intermediate diradical and thus prevents racemization. The synthetic utility of the resulting [2 + 2] cycloadducts was briefly examined. The most notable transformations were conversion of the enolacetate of the spirooxindole to the corresponding ketone and α-acetoxyketone

Dynamic Self-Assembly and Computation: From Biological to Information Systems

Abstract. We present two ways in which dynamic self-assembly can be used to perform computation, via stochastic protein networks and self-assembling software. We describe our protein-emulating agent-based simulation infrastructure, which is used for both types of computations, and the few agent properties sufficient for dynamic self-assembly. Examples of protein-networkbased computation and self-assembling software are presented. We describe some novel capabilities that are enabled by the inherently dynamic nature of the self-assembling executable code

Production of mutants of Gaeumannomyces graminis var. tritici and var. avenae by 4- nitroquinolene-oxide treatment of protoplasts.

The ascomycete fungus Gaeumannomyces graminis is the causative agent of take-all disease of cereals. Much information about the physiology and pathology of this organism has been generated (Asher and Shipton (Eds.) Biology and Control of Take-All , Academic Press, 1981), but genetic studies such as the production of mutants have been hindered by problems in obtaining viable propagules suitable for mutagenesis (Blanch et al. 1981. Trans. Brit. Mycol. Soc. 77:391-399). The fungus is homothallic but many strains cannot be induced to form perithecia in culture and even the fertile strains produce insufficient numbers of ascospores for use in mutagenesis. It is, however, possible to produce and regenerate large numbers of protoplasts and Rochefrette et al

OeBAS and CYP716C67 catalyze the biosynthesis of health-beneficial triterpenoids in olive (Olea europaea) fruits

center dot The bioactive properties of olive (Olea europaea) fruits and olive oil are largely attributed to terpenoid compounds, including diverse triterpenoids such as oleanolic, maslinic and ursolic acids, erythrodiol, and uvaol. They have applications in the agri-food, cosmetics, and pharmaceutical industries. Some key steps involved in the biosynthesis of these compounds are still unknown.center dot Genome mining, biochemical analysis, and trait association studies have been used to identify major gene candidates controlling triterpenoid content of olive fruits.center dot Here, we identify and functionally characterize an oxidosqualene cyclase (OeBAS) required for the production of the major triterpene scaffold beta-amyrin, the precursor of erythrodiol, oleanolic and maslinic acids, and a cytochrome P450 (CYP716C67) that mediates 2 alpha oxidation of the oleanane- and ursane-type triterpene scaffolds to produce maslinic and corosolic acids, respectively. To confirm the enzymatic functions of the entire pathway, we have reconstituted the olive biosynthetic pathway for oleanane- and ursane-type triterpenoids in the heterologous host, Nicotiana benthamiana. Finally, we have identified genetic markers associated with oleanolic and maslinic acid fruit content on the chromosomes carrying the OeBAS and CYP716C67 genes.center dot Our results shed light on the biosynthesis of olive triterpenoids and provide new gene targets for germplasm screening and breeding for high triterpenoid content

Worms:Pernicious parasites or allies against allergies?

Host-parasite interactio

A conserved amino acid residue critical for product and substrate specificity in plant triterpene synthases

Triterpenes are structurally complex plant natural products with numerous medicinal applications. They are synthesized through an origami-like process that involves cyclization of the linear 30 carbon precursor 2,3-oxidosqualene into different triterpene scaffolds. Here, through a forward genetic screen in planta, we identify a conserved amino acid residue that determines product specificity in triterpene synthases from diverse plant species. Mutation of this residue results in a major change in triterpene cyclization, with production of tetracyclic rather than pentacyclic products. The mutated enzymes also use the more highly oxygenated substrate dioxidosqualene in preference to 2,3-oxidosqualene when expressed in yeast. Our discoveries provide new insights into triterpene cyclization, revealing hidden functional diversity within triterpene synthases. They further open up opportunities to engineer novel oxygenated triterpene scaffolds by manipulating the precursor supply

Analysis of Two New Arabinosyltransferases Belonging to the Carbohydrate-Active Enzyme (CAZY) Glycosyl Transferase Family1 Provides Insights into Disease Resistance and Sugar Donor Specificity

Glycosylation of small molecules is critical for numerous biological processes in plants, including hormone homeostasis, neutralization of xenobiotics, and synthesis and storage of specialized metabolites. Glycosylation of plant natural products is usually carried out by uridine diphosphate-dependent glycosyltransferases (UGTs). Triterpene glycosides (saponins) are a large family of plant natural products that determine important agronomic traits such as disease resistance and flavor and have numerous pharmaceutical applications. Most characterised plant natural product UGTs are glucosyltransferases, and little is known about enzymes that add other sugars. Here we report the discovery and characterization of AsAAT1 (UGT99D1), which is required for biosynthesis of the antifungal saponin avenacin A-1 in oat. This enzyme adds L-arabinose to the triterpene scaffold at the C-3 position, a modification critical for disease resistance. The only previously reported plant natural product arabinosyltransferase is a flavonoid arabinosyltransferase from Arabidopsis. We show that AsAAT1 has high specificity for UDP-β-L-arabinopyranose, identify two amino acids required for sugar donor specificity, and through targeted mutagenesis convert AsAAT1 into a glucosyltransferase. We further identify a second arabinosyltransferase potentially implicated in the biosynthesis of saponins that determine bitterness in soybean. Our investigations suggest independent evolution of UDP-arabinose sugar donor specificity in arabinosyltransferases in monocots and eudicots

Brian: The Typographical Error that Brought Early Career Neuroscientists and Artists Together

In the project “Do You Mind?” early career neuroscientists and artists collaborated to produce artworks for exhibition

Linear and Second-order Optical Response of the III-V Mono-layer Superlattices

We report the first fully self-consistent calculations of the nonlinear optical properties of superlattices. The materials investigated are mono-layer superlattices with GaP grown on the the top of InP, AlP and GaAs (110) substrates. We use the full-potential linearized augmented plane wave method within the generalized gradient approximation to obtain the frequency dependent dielectric tensor and the second-harmonic-generation susceptibility. The effect of lattice relaxations on the linear optical properties are studied. Our calculations show that the major anisotropy in the optical properties is the result of strain in GaP. This anisotropy is maximum for the superlattice with maximum lattice mismatch between the constituent materials. In order to differentiate the superlattice features from the bulk-like transitions an improvement over the existing effective medium model is proposed. The superlattice features are found to be more pronounced for the second-order than the linear optical response indicating the need for full supercell calculations in determining the correct second-order response.Comment: 9 pages, 4 figures, submitted to Phy. Rev.