Conformational analysis, organic synthesis

In the post-World War II years, synthesis attained a different level of sophistication partly as a result of the confluence of five stimuli (1) the formulation of detailed electronic mechanisms for the fundamental organic reactions, (2) the introduction of conformational analysis of organic structures and transition states based on stereochemical principles, (3) the development of spectroscopic and other physical methods for structural analysis, (4) the use of chromatographic methods of analysis and separation, and (5) the discovery and application of new selective chemical reagents. As a result, the period 1945 to 1960 encompassed the synthesis of such complex molecules as vitamin A (O. Isler, 1949), cortisone (R. Woodward, R. Robinson, 1951), strychnine (R. Woodward, 1954), cedrol (G. Stork, 1955), morphine (M. Gates, 1956), reserpine (R. Woodward, 1956), penicillin V (J. Sheehan, 1957), colchicine (A. Eschenmoser, 1959), and chlorophyll (R. Woodward, 1960) (page 5). ... 

Problems 1-3 emphasize the three dimensional representation of various cyclic molecules and evaluation of their energies by the A, G, and U parameters. In Problems 4-6, we apply conformational analysis to predict the reactivity of carbocyclic systems toward various reagents and to gather information regarding the preferred stereochemical course of the corresponding reactions. Further examples of applications of conformational analysis in organic synthesis are incorporated in Problems 7-9. 

Vyacheslav V. Samoshin was born in Norilsk, Russian Federation. He graduated with an Honorable Diploma (M.S.) from Moscow State University in 1974. At the same university, he defended his Ph.D. dissertation under the supervision of academician Nikolay S. Zefirov in 1982, and his Doctor of Chemical Sciences dissertation in 1991. He worked as a researcher in the Department of Chemistry, Moscow State University, and since 1992 as professor (head of the Division of Organic Chemistry in Moscow State Academy of Fine Chemical Technology). In 1999, he took his present position as professor of chemistry at the University of the Pacific, Stockton, California. His scientific interests include molecular switches, conformational analysis, synthesis and studies of bioactive compounds, including carbohydrate mimetics, asymmetric synthesis, and synthesis and studies of crown ethers and relative compounds. 

For the pharmacophore-based screening, a 3-D-pharmaco-phore feature is constmcted by structure-activity relationship analysis on a series of active componnds (26) or is dednced from the X-ray crystal stmcture of a ligand-receptor complex (27). Taking this 3-D-pharmacophore feature as a query structure, 3-D database search can be performed to select the molecnles from the available chemical databases, which contain the pharmacophore elements and may conform to the pharmacophore geometric constraints. Then the selected compounds are obtained either from commercial sonrces or from organic synthesis for the real pharmacologic assays (see Fig. 3). 

R. Noyori, Asymmetric Catalysis in Organic Synthesis, John Wiley Sons, New York, 1994. E. Juaristi, Introduction to Stereochemistry and Conformational Analysis, John Wiley Sons, New York, 1991. 

As target molecules of multistep organic synthesis, the molecular structure of the monomers that form synthetic ion channels and pores is always known from routine analytical methods. Structural studies, therefore, ask the question how these monomers form active ion channels and pore, i.e. focus on conformational or supramolecular analysis. Being the outcome of rational design based on known structural information, this question often comes down to the not very inspired question whether or not synthetic ion channels and pores that are already known to function as expected also form the expected active structure. Added to a lipid bilayer, a monomer of known structure can avoid the membrane (Fig. 11.13, Aa) or accumulate in transmembrane orientation (Figure 11.13, Ab), in the middle ofthe... 

ORGANIC STEREOCHEMISTRY - covers conformation and configurational analysis, asymmetric synthesis, and stereochemistry and steric factors in organic reactions. 

The evolution of stereoelectronic concepts was further catalyzed by steroid synthesis and rapid development of conformational analysis recognized by the 1969 Nobel Prize to Barton and Hassel. However, it was not until 1983, that an organized treatise dedicated to stereoelectronics was published (the important books by Deslongchamps and Kirby). 

About the same time, a new international research journal, Carbohydrate Research, appeared (volume 1) in 1964. It has become the principal journal for the publication of all aspects of carbohydrate research, such as chemical synthesis and modification enzymatic synthesis organic and enzymatic mechanisms involving carbohydrates carbohydrate metabolism conformational analysis isolation of carbohydrates from natural sources analytical methods chemistry of monosaccharides, oligosaccharides, and polysaccharides biological function of carbohydrates and physical properties. Approximately four to five volumes are published each year. 

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