This thesis mainly describes the development of a screening process for a mirror-image library of chiral natural products. It demonstrates how, by using mirror-image proteins for the screening of available natural products, unavailable mirror-image isomers of natural products can be screened in a mirror process. Moreover, as mirror-image isomers including target proteins and natural products are mainly prepared by means of chemical synthesis, the screening strategy presented here suggests the importance of organic chemistry.
Natural products are commonly used as valuable resources for drug discovery. However, as they are mostly produced as single enantiomeric forms, researchers have tested only natural products bearing one stereochemistry available in nature. As natural products and their enantiomers have identical physicochemical properties and different biological activities, mirror-image isomers of natural products are promising candidates for novel medicinal resources.
In an effort to identify anticancer agents from the mirror-image library, chemical protein syntheses of some target oncoproteins, MDM2, MDMX and Grb2, and their applications to the chemical array screening process were achieved. In the course of this process the NP843 enantiomer, which is the enantiomer of an α-tocopherol derivative, was successfully identified as a novel MDM2-p53 interaction inhibitor. These results clearly show that a mirror-image library of chiral natural products represents an invaluable medicinal resource. Accordingly, the chemistry-based screening strategy described in this thesis will be of great interest to a broad range of chemists involved in natural product, medicinal, and synthetic chemistry.
More than ever, effective design is the focal point of sound chemical engineering. Analysis, Synthesis, and Design of Chemical Processes, Fourth Edition, presents design as a creative process that integrates both the big picture and the small details–and knows which to stress when, and why. Realistic from start to finish, this updated edition moves readers beyond classroom exercises into open-ended, real-world process problem solving. The authors introduce integrated techniques for every facet of the discipline, from finance to operations, new plant design to existing process optimization.
This fourth edition adds new chapters introducing dynamic process simulation; advanced concepts in steady-state simulation; extensive coverage of thermodynamics packages for modeling processes containing electrolyte solutions and solids; and a concise introduction to logic control. “What You Have Learned” summaries have been added to each chapter, and the text’s organization has been refined for greater clarity.
Coverage IncludesConceptualization and analysis: flow diagrams, batch processing, tracing, process conditions, and product design strategies Economic analysis: capital and manufacturing costs, financial calculations, and profitability analysis Synthesis and optimization: principles, PFD synthesis, simulation techniques, top-down and bottom-up optimization, pinch technology, and software-based control Advanced steady-state simulation: goals, models, solution strategies, and sensitivity and optimization studies Dynamic simulation: goals, development, solution methods, algorithms, and solvers Performance analysis: I/O models, tools, performance curves, reactor performance, troubleshooting, and “debottlenecking” Societal impact: ethics, professionalism, health, safety, environmental issues, and green engineering Interpersonal and communication skills: improving teamwork and group effectiveness
This title draws on more than fifty years of innovative chemical engineering instruction at West Virginia University and the University of Nevada, Reno. It includes suggested curricula for single-semester and year-long design courses, case studies and practical design projects, current equipment cost data, and extensive preliminary design information that can be used as the starting point for more detailed analyses.
About the CD-Rom and Web Site
The CD contains the newest version of CAPCOST, a powerful tool for evaluating fixed capital investment, full process economics, and profitability. The heat exchanger network software, HENSAD, is also included. The CD also contains an additional appendix presenting preliminary design information for fifteen key chemical processes, including four new to this edition: shift reaction; acid-gas removal via physical solvent; H2S removal from a gas stream using the Claus process; and coal gasification. The CD also includes six additional projects, plus chapters on outcomes assessment, written and oral communications, and a written report case study. Sixty additional projects and twenty-four more problems are available at www.che.cemr.wvu.edu/publications/projects.