Mixed synthesis

Quench Converter. The quench converter (Fig. 7a) was the basis for the initial ICl low pressure methanol flow sheet. A portion of the mixed synthesis and recycle gas bypasses the loop interchanger, which provides the quench fractions for the iatermediate catalyst beds. The remaining feed gas is heated to the inlet temperature of the first bed. Because the beds are adiabatic, the feed gas temperature increases as the exothermic synthesis reactions proceed. The injection of quench gas between the beds serves to cool the reacting mixture and add more reactants prior to entering the next catalyst bed. Quench converters typically contain three to six catalyst beds with a gas distributor in between each bed for injecting the quench gas. A variety of gas mixing and distribution devices are employed which characterize the proprietary converter designs. 

The solid-phase technique of split and mix synthesis relies on the efficiency of mixture-based synthesis to provide very large libraries (millions) of discrete compounds (Figure 4).[161 In this approach, each resin bead is treated with a single building block for each synthesis step. Thus any single resin bead possesses identical copies of one library member, but the identity of the library member on any bead is lost due to the mix step of the process. Elegant strategies have been developed to chemically encode the syn-... 

The synthesis of libraries of structurally defined compounds can potentially be achieved either by split-mix synthesis or by parallel synthesis of individual compounds. The synthesis requires a reliable methodology of oligosaccharide synthesis, where stereochemistry and regioselectivity have to be achieved unlike other library approaches. Development of synthetic methodologies that can provide access to any oligosaccharide structure is underway. 

Depending on the substituent R1 (CH3, CF3, Cl, Br, N(CH3)2), the resulting reddish yellow to bluish violet pigments show excellent lightfastness and weatherfastness and very good migration fastness. If two differently substituted benzoni-triles are used, the product is a mixture of the symmetrically substituted and the two unsymmetrically substituted diphenyl-DDP pigments (mixed synthesis). 

Another path affording novel pigments is the mixed synthesis yielding solid solutions. The mixed synthesis of two DPP pigments can result in solid solutions, which consist of the two symmetrically and the unsymmetrically substituted DPP pigment. Solid solutions can also be obtained from DPP pigments and quin-acridone pigments. 

The split-mix synthesis technique can allow geometric numbers of compounds to be prepared using an arithmetic number of reaction chambers.5... 

Split-Mix Synthesis Using Macroscopic Solid Support Units... 

We first reported the one-bead one-compound (OBOC) combinatorial library method in 1991.1 In this method, compound beads are prepared by a split-mix synthesis approach1 3 (Fig. 1) that results in the display of many copies of the same compound on one single bead.1,4 Tens of thousands to millions of these compound beads can easily be prepared. The bead library is then mixed with a target molecule, such as a protein, an... 

Fig. 1. Split/mix synthesis approach to generate an OBOC combinatorial library.

The expense of screening depends very much on the number of samples tested. Consequently, the density format of titer-plates has increased in recent years from 96-well up to the 9600-well format. The next big step towards miniaturization would be the complete avoidance of any container, which then results in the smallest well possible and a well-less, so-called lawn-format assay develops. This is exactly what is proposed by a number of authors (see review [47]). Screening in a lawn format does not mean avoiding any structure or arrangements. Samples are still prepared on beads, which are produced by split-mix synthesis, but the beads are arrayed directly on the well-less assay. A typical matrix applied for such biological screening is the agarose lawn. Active beads are then picked from the assay matrix and decoded for compound identification. 

For all of the above good reasons, few publications have come out on combinatorial mixture analysis in this review period. Mixture analysis of peptides by MS and MS/MS has continued as an active field [2,59,64], Nanospray (very low flow electrospray) has become the method of choice for studies of mixtures of peptides by MS/MS [65,66], 2D NMR has been used to assure that unusual amino acids were correctly incorporated in a mixed synthesis [59]. 

Combinatorial chemistry is the production of libraries of compounds that represent permutations of a set of chemical variables. These variables include the nature of the substituent in a particular molecule, both in type and size, changes in the components in a mixture of materials, e.g. in ceramics and changes in process parameters, e.g. temperature, pH etc. Chemical libraries are usually created by one of two methods split and mix or parallel synthesis . Split and mix synthesis is used to produce small quantities of a relatively large number of compounds and requires assays to be performed on pools of compounds. Parallel synthesis is used to produce libraries... 

FIGURE 2.2 Scheme of the split-mix synthesis. The triangles represent the solid support. The white, gray and black circles are amino acids or other kinds of monomers. 

The split-mix synthesis has several key features that are crucial in the utility of the method in drug discovery or other kinds of applications. 

The combinatorial principle embodied in the synthesis captured the imagination of many researchers all over the world and had a profound effect on the development of the field. The combinatorial nature of the product of the split-mix synthesis is also reflected in its name, combinatorial library. ... 

In the split-mix synthesis, like in other solid phase procedures, the beads behave very much like tiny reaction vessels, which do not interchange their contents with the other ones. Each of the millions of these reaction vessels preserves its content until the end of the synthesis, when they become containers of a single substance. If peptides are produced, their identity can be determined by automatic sequencing [9], It is sufficient to sacrifice a fraction of the total quantity for this purpose. All this means that the split-mix synthesis is, in fact, a parallel procedure, with unprecedented efficiency, however, leading to individual compounds. This feature of the split and mix synthesis allows screening the products in three different ways ... 

A. Split-Mix Synthesis Using Resin Enclosed in Radiofrequency-Encoded Capsules... 

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