Array synthesis

Structure-Based, Structure-Guided Array Synthesis. 190... 

It is particularly effective to pair structure-based design with array synthesis. A relatively larger virtual library of possible analogs can be docked into the structure and the analogs prioritized for synthesis or eliminated if scored low. 

Parallel array synthesis was used to access the 3-aryl-tetrahydro-l,2-diazepines 90 (and other related compounds) by cyclisation of the chloro ketones 88 on reaction with hydrazine to give 89 followed by sulfonamide formation the Si-TrisAmine was added at the end as a scavenger to remove any unreacted arylsulfonyl chloride remaining <06MCL3777>. 

Robert (Bob) Matson, Ph.D., is a senior staff scientist in the Advanced Technology Center at Beckman Coulter, Inc., Fullerton, California. He has been involved in the development of both nucleic acid and protein array-based technology for the past 13 years. His initial introduction to array technology began in collaboration with Sir Edwin Southern in developing an in situ oligonucleotide array synthesis platform for the corporation. Later work by Dr. Matson and his research team produced some of the first plastic microplate-based microarrays. Beckman Coulter recently launched the pi te based upon the microplate "array of arrays" concept. 

Polymer-assisted methodology has been used several times for parallel-array synthesis of libraries involving three to five synthetic steps. Scheme 11 shows a three-step solution-phase synthesis of 2-thioxo-4-dihydro-pyrimid-inones wherein the key purification step involved amine resin 1 to sequester excess aldehydes and isot,hiocyanates from upstream transformations. Thermal cyclization of the purified intermediates gave the desired 2-thioxo-4-dihydropyrimidinones in excellent yields and purities.83... 

Y. Chapleur and M.-N. Euvrard, Hetero Diels-Alder reactions in carbohydrate chemistry A new strategy for multichiral arrays synthesis, J. Chem. Soc. Chem. Commun. p. 884 (1987). 

PNA oligomers have been synthesized by either Boc[31"33] or Fmoc134 methods on polymer beads. The Fmoc method has also been used in array synthesis of PNAsJ8,35 The synthesis of PNA/DNA chimera requires base-labile protection groups on the PNA nucleobases and will not be discussed herein.b-3S 3Sl... 

Another useful scaffold, discovered recently by chance in our laboratories during an array synthesis, is now available for combinatorial chemistry [12]. All wells containing 2-picolinic amine reacted in an unexpected way. Detailed inspection of these reactions provided a novel MCR towards 1,2,4-trisubstituted lH-imidazol-4-yl-pyridines. Typical examples and their yields are given in Scheme 3.7. During... 

Scheme 3.6. The array synthesis of a-amino acids with aldehydes and isocyanides in the case of cinnamic aldehydes did not afford the expected products but rather the methanol adducts.

An extension of and systematic approach towards discovery by chance is the use of combinatorial chemistry. In a seminal paper [14], Weber and Lacke described a systematic approach involving array synthesis in order to discover novel MCRs. In this... 

Molecules containing this substituted piperazine core are important pharmacophores (particularly for GPCR related ligands) and have been reported in several drugs under development [95]. Scientists at Merck recently introduced a novel one-pot isocyanide-based MCR affording the desired substituted piperazine, reportedly compatible with array synthesis. 

One form of combinatorial chemistry involves parallel synthesis or array synthesis. In parallel synthesis, each new compound is formed in its own miniature reactor or well. If a new library is to contain 500 members, synthesis of the library will require 500 wells in the final step. For this reason, parallel synthesis is associated with the phrase one compound-one well. 

One way to use a photoresist film for array synthesis is to employ the image-patterned film as a physical barrier to mask selected regions of the substrate from exposure to reagents used in DNA synthesis. Figure 4A (Left) outlines a... 

The latter approach has been exemplified in a number of published cases. An indication of the development requirements of well-known reactions for successful employment in array synthesis is provided by the work ofWatson and co-workers [15] to prepare thiazole derivatives. Adaptation of the Hantzch synthesis of 2-aminothiazoles (Fig. 2) from a-haloketones and thioureas was used in the one-step preparation of discrete samples. Inclusion in the array of a compound of known biological activity provided a valuable internal control. 

Grimes CA, Mor GK. Ti02 nanotube arrays synthesis, properties, and applications. Heidelberg Springer 2009. 

Figure 7 (a) Pyrazinone scaffold identified incorporating three points of variation, (b) Lead compound arising from PASP array synthesis... 

Combinatorial library design approaches have been discussed (94), with the design of library subsets that simultaneously optimize the diversity or similarity of a library to a target, properties (such as druglikeness) of the library members, properties (such as cost or availability) of the reactants required to make them, and the efficiency for array synthesis. They showed that libraries can be designed to... 

The spot synthesis technique is simple and easily accessible for practical use. There are some limitations to the scope of chemistries that can be used with cellulose as a solid support. To eliminate some of these shortcomings, Gao and EsnoufP° 4 proposed using a different membrane, Immobilon AV-1, for spot synthesis. Before the synthesis of peptide arrays can be carried out, this polyvinylidene fluoride based material is derivatized with ethane-1,2-diamine, followed by coupling of Fmoc-(3Ala as a spacer. In most other aspects, this peptide array synthesis is very similar to the spot synthesis proposed by Frank.t l... 

Department of Molecular Biology Glycan Array Synthesis Core D Consortium for Functional Glycomics The Scripps Research Institute La Jolla, CA 92037 USA... 

Array synthesis The form of parallel synthesis in which the reaction vessels are maimained in a particular spatial arrange-mem, such as a grid in a microtiter plate. Such arrays genentted on a microscopic basis arc termed a sitatially addresstdtk library. 

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