Synthetic constraints

Synthetic constraints—such as difficulty, yield, management of starting materials, and intermediates—will naturally restrict the diversity of compounds that are made [7]. In silico designs with scaffolds that utilize similar synthetic steps will naturally be favored over those that are not. These pressures to make a small number of compounds with limited scaffold variability require computational methods to make exquisitely accurate predictions The... 

Product-based approaches can be divided into those that take the combinatorial constraint into account such that each reactant in one pool appears in a product with every reactant from every other reactant pool, and those that merely pick product molecules without consideration of the synthetic constraint. The latter approach is often referred to as cherry-picking and is synthetically inefficient as far as combinatorial synthesis is concerned. In this chapter the emphasis is on product-based library design methods that take the combinatorial constraint into account. 

There are, however, synthetic constraints on the use of anhydro sugars as a source of polysaccharides, because chain-growth processes generally lead to the formation of homopolymers only, or, if two or more monomers are used, to the formation of random copolymers. In these processes, the polymer composition and mer sequence-... 

Operational Constraints and Problems. Synthetic ammonia manufacture is a mature technology and all fundamental technical problems have been solved. However, extensive know-how in the constmction and operation of the faciUties is required. Although apparendy simple in concept, these facihties are complex in practice. Some of the myriad operational parameters, such as feedstock source or quaUty, change frequendy and the plant operator has to adjust accordingly. Most modem facihties rely on computers to monitor and optimize performance on a continual basis. This situation can produce problems where industrial expertise is lacking. 

Syntheses of radioactive tracers involve all of the classical biochemical and synthetic chemical reactions used in the synthesis of nonradio active chemicals. There are, however, specialized techniques and considerations required for the safe handling of radioactive chemicals, strategic synthetic considerations in terms of their relatively high cost, and synthesis scale constraints governed by specific activity requirements. 

Although one of the two building blocks has to be symmetric to avoid constitutional isomers, the symmetry constraints differ from those of the 2 + 2 approach and this allows the synthesis of structures that would be difficult to obtain by other synthetic strategies. Consequently, the 3 + 1 strategy has been accepted and is an increasingly used method for porphyrin synthesis.49... 

In view of these constraints, we recently suggested a different strategy for the improvement of the material properties of synthetic poly (amino acids) (12). Our approach is based on the replacement of the peptide bonds in the backbone of synthetic poly(amino acids) by a variety of "nonamide" Linkages. "Backbone modification," as opposed to "side chain modification," represents a fundamentally different approach that has not yet been explored in detail and that can potentially be used to prepare a whole family of structurally new polymers. 

A more recent approach, which also profits from the synthetic versatility of stabilized thionium ions, has been elaborated by Berard and Piras [22]. These authors observed that the cyclobutane thionium ions 1-76 obtained from the cyclopropyl phenyl sulfides 1-75 by treatment with pTsOH under anhydrous conditions can be trapped by an adjacent electron-rich aromatic ring to give the chromane derivatives 1-77 in good to excellent yields (Scheme 1.20). As expected, 1-77 were obtained as single diastereoisomers with a ds-orientation of the methyl and the phenylthio group as a consequence of steric constraints. 

Synthetic chemists desire well defined reaction conditions. Process chemists demand them. Nonuniform heating and difficulties with mixing and temperature measurement are technical constraints that initially limited the scale of microwave chemistry with dry media and have not yet been overcome. Poor reproducibility also has been reported, probably resulting from differences in performance and operation of individual domestic microwave ovens [13-15]. Consequently, most, if not all, of the disclosed applications of dry media are laboratory-scale preparations. However, as discussed in other chapters, this does not prevent their being interesting and useful. 

In view of the size of operation being contemplated, it is unlikely that homogeneous catalysts will play a primary role in the production of synthetic oil. However, from the standpoint of the chemical industry, the complex mixture of products obtained from the classical Fischer-Tropsch process is generally unattractive owing to the economic constraints imposed by costly separation/purification processes. What is needed is a catalyst system for the selective conversion of CO/H2 mixtures to added-... 

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