Parallel spatially addressable

Fodor, S. P. (1991). Light-directed, spatially addressable parallel chemical synthesis. Science 251, 767-773. 

An 8000-member library of trisamino- and aminooxy-l,3,5-triazines has been prepared by use of highly effective, microwave-assisted nucleophilic substitution of polypropylene (PP) or cellulose membrane-bound monochlorotriazines. The key step relied on the microwave-promoted substitution of the chlorine atom in monochlorotriazines (Scheme 12.7) [35]. Whereas the conventional procedure required relatively harsh conditions such as 80 °C for 5 h or very long reaction times (4 days), all substitution reactions were found to proceed within 6 min, with both amines and solutions of cesium salts of phenols, and use of microwave irradiation in a domestic oven under atmospheric reaction conditions. The reactions were conducted by applying a SPOT-synthesis technique [36] on 18 x 26 cm cellulose membranes leading to a spatially addressed parallel assembly of the desired triazines after cleavage with TFA vapor. This concept was later also extended to other halogenated heterocycles, such as 2,4,6-trichloropyrimidine, 4,6-dichloro-5-nitropyrimidine, and 2,6,8-trichloro-7-methylpurine, and applied to the synthesis of macrocyclic peptidomimetics [37]. 

Parallel synthesis is the term loosely applied to the preparation of discrete compounds in the format of a spatially addressable array. It is often used in contrast to "mixture-based" combinatorial synthesis. While it is hue that the term "parallel synthesis" may encompass the preparation of a fully combinatorial multidimensional array of compounds, in practice, it most... 

Direct electrochemical amide oxidation reactions have also been employed in parallel synthesis using a spatially addressable electrochemical platform [107]. In this work, an electrolysis platform was set up so that 16 electrochemical reactions could be run in parallel at the same time. The cells were set up in a 4 by 4 array in which each cell was equipped with a... 

In-situ photofabrication of OND arrays involves light-directed, spatially addressable, parallel (combinatorial) chemical synthesis [35,43,66-68]. A surface, usually a sihcon wafer or a glass slide, is coated with hnker molecules... 

I-odor. S P A. 01 at. "Light-Directed. Spatially Addressable Parallel Chemical Synthesis.". Vcienee, 767 (February IS. 19911 Jam>ld. M.F. "Nanosurfaee Clietnisiry on Size-Selected Silicon C liniers." Seitner. 1085 tMay 14. 1991). 

In Scheme 9.4, a three-component synthesis using an amine, acid chloride, and alkyl halide is shown. If this process were started with two amines (Ai and A2), two acid chlorides (Cj and C2), and two alkyl halides (Hj and H2), eight (23) new amides may be formed (Scheme 9.5). Such a synthesis would require eight wells. The reagents would be dispensed in a pattern to generate all possible combinations. At the end of the synthesis, the exact position and contents of each well would be known. Therefore, parallel synthesis is often referred to as a spatially addressable method. Any particular compound may be accessed directly and immediately. 

Regardless of how the products are isolated and purified, all parallel syntheses hold to the concepts of one compound-one well and spatial-addressability. Differences between various parallel syntheses are discemable based on whether the synthesis is performed in a solution-phase or solid-phase manner. 

A microfluidic system was made consisting of a Y-type channel structure and a packed bed of micro beads in a zone in the center of the outlet channel [162]. At the end of the micro-bead bed a weir is placed. The outlet channel then reopens to a larger flow zone which has several parallel micro channels, splitting the main flow into many sub-streams. These micro channels serve as spatially addressable detection lanes. 

In this chapter we will discuss current approaches for analytical characterization of combinatorial libraries in a pharmaceutical industry environment. Recently, several analytical groups have presented very similar strategies for analysis of libraries [7-9]. As will be shown later, the key to successful analytical characterization of a combinatorial library is to perform analytical and chemical work in parallel with the library development. The accumulation of data and analytical experience during this process results in an assessment of library quality with a high level of confidence, even if as little as 5-10% of the library components are analyzed. Utilization of the strategy will be demonstrated using two examples analysis of a library synthesized on a robotic station in spatially addressed format and analysis of a library synthesized in accordance with split-and-mix technology. 

In essence only two approaches exist to generate combinatorial peptide libraries biologic and synthetic library approaches. According to the different techniques used, the synthetic library approach can be divided additionally into five methods 1) the spatially addressable parallel library method (1, 4, 8),... 

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