C???H oxidation reactions in complex molecule synthesis: application and development

Among the frontier challenges in chemistry in the 21st century are the interconnected goals of increasing synthetic efficiency and diversity in the construction of complex molecules. Oxidation reactions of C???H bonds, particularly when applied at late-stages of complex molecule syntheses, hold special promise for achieving both these goals by minimizing the use of functional group manipulations typically required to synthesize these molecules. Traditionally, C???H oxidation reactions install oxidized functionality onto a preformed molecular skeleton, resulting in a local molecular change. However, the use of C???H activation chemistry to construct complex molecular scaffolds is a new area with tremendous potential in synthesis. This work showcases a late-stage C???H oxidation strategy in the total synthesis of 6-deoxyerythronolide B (6-dEB), the aglycone precursor to the erythromycin antibiotics. An advanced intermediate is cyclized to the 14-membered macrocyclic core of 6-dEB using a late-stage (step 19 of 22) C???H oxidative macrolactonization reaction that proceeds with high regio-, chemo-, and diastereoselectivity (>40:1). A chelate-controlled model for macrolactonization predicted the stereochemical outcome of C???O bond formation and guided the discovery of conditions for synthesizing the first diastereomeric 13-epi-6-dEB precursor. Overall, this C???H oxidation strategy affords a highly efficient and stereochemically versatile synthesis of the erythromycin core. Throughout the erythromycin???s rich synthetic history, no concept has been entrenched as deeply as the perceived need for biasing elements in order to effect 14-membered macrocyclization. This work showcases the cyclizations of completely unbiased 6-deoxyerythronolide B precursors, using either C???H oxidative or Yamaguchi macrolactonization reactions. Late-stage and stereodivergent C???H oxidation reactions enabled seco acid formation with both configurations at C13. Consequently, it is shown that both the natural and unnatural C13 configurations can be formed in the macrocyclization of the 6-dEB core in the absence of preorganizational elements. Overall these findings require revision of the 30-year-old dogma that preorganization is mandatory for achieving macrocyclization of the erythromycins. Sequential transformations in a single reaction have the potential to dramatically increase synthetic efficiency by rapidly building molecular complexity while lowering step count and intermediate isolations. Catalytic dehydrogenation reactions of hydrocarbons represent a powerful reaction class capable of activating an otherwise non-reactive substrate through sequential C???H bond activations. As a result, coupling a dehydrogenation transformation to a complexity generating reaction would lead to complex molecular architectures from topologically simple starting materials in a rapid fashion. We report a Pd(II)/bis-sulfoxide catalyzed dehydrogenative Diels-Alder reaction that converts simple terminal olefins into complex cyclohexenyl adducts in good yields and selectivities. Based on the high functional group tolerance, this method enables expedient access to a wide variety of biologically and medicinally relevant heterocycles, such as hydroisoindolines, cis-decalins, hydroisoquinolines, and isoindoloquinolines. Mechanistic studies indicate the reaction proceeds through a sequential allylic C???H cleavage and homoallylic ??-hydride elimination to produce a mixture of E and Z terminal 1,3-dienes, which isomerize to the Diels-Alder capable (E)-isomer via Pd(II)-catalysis, followed by a thermal Diels-Alder cycloaddition

Review and statistical analysis of the ultrasonic velocity method for estimating the porosity fraction in polycrystalline materials

A review and statistical analysis of the ultrasonic velocity method for estimating the porosity fraction in polycrystalline materials is presented. Initially, a semi-empirical model is developed showing the origin of the linear relationship between ultrasonic velocity and porosity fraction. Then, from a compilation of data produced by many researchers, scatter plots of velocity versus percent porosity data are shown for Al2O3, MgO, porcelain-based ceramics, PZT, SiC, Si3N4, steel, tungsten, UO2,(U0.30Pu0.70)C, and YBa2Cu3O(7-x). Linear regression analysis produced predicted slope, intercept, correlation coefficient, level of significance, and confidence interval statistics for the data. Velocity values predicted from regression analysis for fully-dense materials are in good agreement with those calculated from elastic properties

Pentingnya Kolaborasi Stakeholder dalam Mewujudkan Terminal Sehat di Sulawesi Selatan

Healthy cities merupakan isu yang sangat kompleks, melibatkan banyak sektor dan berbagai disiplin ilmu, olehnya itu healthy cities hanya bisa dicapai kalau semua sektor yang terlibat dapat berkolaborasi dengan baik. Penelitian ini bertujuan untuk mengetahui cara yang dinilai efektif untuk mewujudkan terminal sehat. Penelitian ini menggunakan penelitian kualitatif dengan pendekatan participation action research (PAR). Pengumpulan data dilakukan melalui focus group discussion (FGD), wawancara mendalam. Informan penelitian yaitu ketua Persatuan Penyandang Disabilitas Sulawesi Selatan, Ketua Organisasi Angkutan Darat, perwakilan Solidaritas Perempuan Sulawesi Selatan, pengguna terminal, koordinator kebersihan Terminal, Humas Terminal, Direktur Operasional Terminal, ahli kesehatan masyarakat, pedagang dan Direktur Utama Terminal. Hasil FGD berkesimpulan bahwa kolaborasi stakeholder adalah kunci sukses dalam mewujudkan konsep terminal sehat

Coupled hygrothermal, electrochemical, and mechanical modelling for deterioration prediction in reinforced cementitious materials

In this paper a coupled hygrothermal, electrochemical, and mechanical modelling approach for the deterioration prediction in cementitious materials is briefly outlined. Deterioration prediction is thereby based on coupled modelling of (i) chemical processes including among others transport of heat and matter as well as phase assemblage on the nano and micro scale, (ii) corrosion of steel including electrochemical processes at the reinforcement surface, and (iii) material performance including corrosion- and load-induced damages on the meso and macro scale. The individual FEM models are fully coupled, i.e. information, such as such as corrosion current density, damage state of concrete cover, etc., are constantly exchanged between the models

The structure of flower visitation webs: how morphology and abundance affect interaction patterns between flowers and flower visitors

Interaction patterns between plants and flower visitors in a Mediterranean flower visitation web can be explained surprisingly well by the combination of two simple mechanisms. Firstly, the size threshold that the nectar tube depth of flowers puts on the tongue length of potential flower visitors; and secondly, random interactions proportional to the frequency of tube depths and tongue lengths in the local species pool. Simulation models revealed that the combination of these factors can reproduce the observed variation in the number of interaction partners, the observed asymmetry of plant - flower visitor interactions, and the degree of morphological matching between tube depth and proboscis length. The study shows also that the frequency distributions of tongue lengths and tube depths have a profound influence on the interaction patterns. The shapes of the observed trait distributions resemble ubiquitous lognormal body size distributions. Knowledge about the structure of flower visitation webs and the underlying causes is essential for understanding the evolution of plants and their pollinators. It also provides an important tool for biodiversity conservation.LEI Universiteit LeidenPlantenecologi

Coupled hygrothermal, electrochemical, and mechanical modelling for deterioration prediction in reinforced cementitious materials

In this paper a coupled hygrothermal, electrochemical, and mechanical modelling approach for the deterioration prediction in cementitious materials is briefly outlined. Deterioration prediction is thereby based on coupled modelling of (i) chemical processes including among others transport of heat and matter as well as phase assemblage on the nano and micro scale, (ii) corrosion of steel including electrochemical processes at the reinforcement surface, and (iii) material performance including corrosion- and load-induced damages on the meso and macro scale. The individual FEM models are fully coupled, i.e. information, such as such as corrosion current density, damage state of concrete cover, etc., are constantly exchanged between the models

An investigation of gender, perceived gender-barriers to a future occupation, and academic achievement among delinquent adolescents

The current study assesses perceptions of gender-related barriers to a future occupation and its association with academic achievement among delinquent adolescents aged 12-19 years old. It was hypothesized that the perception of gender related barriers to a future occupation would have similar effects on male and female adolescents\u27 academic achievement. Data included self-reported perceived barriers to a future occupation and academic achievement. Results indicated that females and males reported similar amounts of perceived barriers to a future occupation. Regression analysis indicated the relationship between perceived barriers and academic achievement varied across gender. For males, more perceived gender-barriers were associated with lower academic achievement, whereas, for females gender-barriers did not predict academic achievement. Although our hypothesis was not supported, the findings reveal an interesting phenomenon provoking the need for further study of gender, perceived barriers, and academic outcomes in delinquent populations

Review and Statistical Analysis of the use of Ultrasonic Velocity for Estimating the Porosity Fraction in Polycrystalline Materials

The physical behavior of components manufactured from polycrystalline materials is in many cases directly dependent on the porosity fraction (volume fraction of pores). As examples concerning key properties of technologically-important materials, porosity fraction has been shown to affect (1) the strength, toughness and modulus of structural and refractory materials such as Steel [1], Tungsten [2], SiC [3], Si3N4 [3], and Al2O3 [3], (2) the strength of nuclear fuel materials such as UO2 [4–5]. (3) the thermal shock behavior and strength of porcelain-based ceramics [6–7], (4) the dielectric and elastic properties of piezoelectric materials such as PZT [8], and (5) the critical current density, diamagnetic response, and modulus of superconducting ceramics such as YBa2Cu3O7−x [9–11]. In such cases where physical properties are directly dependent on porosity fraction, the measurement of porosity fraction becomes important in the quality assurance process for the material