Chemical feasibility

Physticochemical coiiatrainla Further constraints can be imposed on the atoms and bonds of the reaction center, such as those physicochemical factors calculated by the PETRA package (see Section 7.1). For example, the partial charges calculated by the PEOE method can be used to extract the chemically feasible reaction from the two conceivable ones as illustrated in Figure 10.3-11. 

A significant problem is the dehydrocoupling reaction, which proceeds only at low yields per pass and is accompanied by rapid deactivation of the catalyst. The metathesis step, although chemically feasible, requires that polar contaminants resulting from partial oxidation be removed so that they will not deactivate the metathesis catalyst. In addition, apparendy both cis- and /ra/ j -stilbenes are obtained consequendy, a means of converting the unreactive i j -stilbene to the more reactive trans isomer must also be provided, thus complicating the process. 

Enantioselective processes involving chiral catalysts or reagents can provide sufficient spatial bias and transition state organization to obviate the need for control by substrate stereochemistry. Since such reactions do not require substrate spatial control, the corresponding transforms are easier to apply antithetically. The stereochemical information in the retron is used to determine which of the enantiomeric catalysts or reagents are appropriate and the transform is finally evaluated for chemical feasibility. Of course, such transforms are powerful because of their predictability and effectiveness in removing stereocenters from a target. 

In summary, modem synthetic methodology allows the stereoselective generation of one, two, or even more stereocenters in a single reaction with or without spatial control by the substrate. The application of transforms to retrosynthetic simplification of stereochemistry requires the selection of transforms on the basis of both structural and stereochemical information in the target and also validation of the corresponding synthetic processes by analysis for both chemical feasibility and stereoselectivity. 

In the above MILP-optimization problem, Euler s theorem for the generation of stable and feasible molecular structures (fully connected graphs) needs to be added as a condition in order to ensure the generation of chemically feasible molecules. This condition is mathematically formulated as,... 

The solution of the MILP-optimization problem gave the candidate solvents shown in Figure 2 (drawn in IUPAC form). The results from GAMS is given in the Appendix. It is important to note that none of these molecular structures are commercially available. Therefore, in order to test them, it is first necessary to synthesize them. Consequently, steps 5-6 have not been performed for these molecules. It is, however, very likely that these molecules will be chemically feasible and stable. 

A major task in program development is therefore, to find ways of automatically extracting the chemically feasible reactions from amongst the formally conceivable ones. To this end a modelling of chemical reactivity seems indispensable. 

A and an r-space interval of 2 A, application of the Nyqvist theorem limits the free parameters to 14. Finally, the chemical feasibility of the fit should be examined. If the number of free parameters is not limited, it is possible to fit any EXAFS spectrum to a high level of apparent precision, and it is this observation that has given EXAFS a poor reputation in the past. 

Phase 2 Demonstrating the chemical feasibility of the key step-which often is the catalytic reaction-and showing that the catalytic step fits into the overall synthetic scheme. 

Finally, ordered water molecules were added to the model where unexplained electron-density was present in chemically feasible locations for water molecules. Temperature factors for these molecules (treated as oxygen atoms) were allowed to refine individually. If refinement moved these molecules into unrealistic positions or increased their temperature factors excessively, the molecules were deleted from the model. Occupancies were constrained to 1.0 throughout the refinement. This means that B values reflect both thermal motion and disorder (Section II.C). Because all B values fall into a reasonable range, the variation in B can be attributed to thermal motion. Table 8.2 shows the progress of the refinement. 

A modelling and experimental effort has identified a new uranium thermochemical cycle (UTC) for the production of hydrogen from water. The peak temperature within the cycle is below 700°C - a temperature achievable with existing high temperature nuclear reactors and some solar systems using commercially auailable materials. This paper describes the new process and some of the experimental work. It is an early report of chemical feasibility. Much work will be required to determine engineering and economic viability. 

Melendez-Hevia, E., T.G. Waddell, and M. Cascante (1996). The puzzle of the Krebs citric acid cycle Assembling the pieces of chemically feasible reactions and opportunism in the design of metabolic... 

From a thermodynamic point of view, many water-splitting cycles are possible and have been proposed chemical feasibility, thermal efficiency and engineering and cost considerations have gradually enacted a selection mechanism and only few cycles are actively being studied today. 

Applying the general reaction schemes contained in our program system onto the bonds of molecules allows the generation of all conceivable reactions or retro-reactions of these molecules. The task is then to select the chemically feasible reactions from the set of the mathematically possible ones. Here lie the main efforts in... 

Scaffold proposals were collected and reviewed according to privileged ion channel motifs, chemical feasibility, and fit to our multiple pharmacophores. Building block selection, virtual library design, and filtering yielded small virtual libraries suitable for automated solution-phase synthesis. All synthesized compounds were finally purified and characterized prior to addition to our focused library. 

A subtle, but no less profound effect of this completely new approach is in the way chemists handle the vocabulary of their profession, a knowledge of possible chemical transformations. It could be said that it will become less important to memorise lists of synthetic methods, but this creates a problem. Computer reaction databases are only as good as the questions we ask them, and without a sound knowledge of what is chemically feasible, we cannot construct a query to obtain the exact reaction conditions we need. 

Finally, there has been speculation and recent experimental support for the involvement of a Nazarov-type cyclization in the biosynthesis of c/ s-jasmonic acid ° and marine-derived prostanoids. Radiolabel tracer studies have demonstrated Ae intermediacy of 8-HPETE (104) in the biosynthesis of prostanoid intermediate preclavulone A (lO ). This remarkable conversion was proposed to proceed by formation of allene oxide (105) followed by isomerization to (107) via the 2-oxidocyclopentadienyl cation (106 Scheme 41). To demonstrate the chemical feasibility of this proposal, Corey reported the transformation of epoxysilane (108) to, inter alia, the cyclopentenone (111 Scheme 42). The reaction is presumed to involve formation of the allene oxide (109) followed by isomerization to the 2-oxi-dopentadienylic cation (110). Conrotatory closure of (110) is expected to produce the cis isomer of (111) as observed. 

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