Automated synthesizer

One widely used method of formation of protected compounds involves polymer-supported reagents, with the advantage of simple workup by filtration and automated syntheses, especially of polypeptides. Polymer-supported reagents are used to protect a terminal — COOH group as a polymer-bound ester (RCOOR —( ) during peptide syntheses, to protect primary alcohols as... 

One widely used method involving protected compounds is solid-phase synthesis (polymer-supponed reagents). This method has the advantage of requiring only a simple workup by filtration such as in automated syntheses, especially of polypeptides, oligonucleotides, and oligosaccharides. 

The ability to manufacture oligos of specified nucleotide sequence is relatively straightforward using automated synthesizers. 

These results demonstrate that O-glycosyl trichloroacetimidate-based oligosaccharide synthesis on solid support may eventually become a valuable alternative to solution-phase synthesis because useful experience is available for the selection of the polymer support and choice of the linker system and the glycosyl donor. Further standardization of the building blocks and the protective group pattern will finally provide the yields and the anomeric control in order to successfully plan automated syntheses of oligosaccharides also in a combinatorial manner. 

A one pot formation and purification of a 5-arylidine 4-thiazolidinone library has also been reported using polymer scavenging as the principle method of purification. An automated synthesizer was employed to make a parallel array of 4080 4-thiazolidinones, prepared simultaneously from a 3-component condensation of mercaptoacetic acid with an amine and a carbonyl compound. Further structural decoration was then introduced using the libraries from libraries principle where the core template was derivatized via an aldol reaction with a second carbonyl unit at the 5-methylene position (Scheme 2.57) [84]. After both synthetic steps. 

Fig. 4 Illustration of (a) Chemspeed automated synthesizer and (b) Symyx batch polymerization system for synthesis of discrete polymer libraries. Reprinted with permission from [90], (Copyright 2007 Taylor Francis Group, http //www.informaworld.com)...

Zhang H, Fijten MWM, Hoogenboom R, Schubert US (2003) Atom-transfer radical polymerization of methyl methacrylate utilizing an automated synthesizer. ACS Symp Ser 854 193-205... 

Hoogenboom R, Fijten MWM, Schubert US (2004) The effect of temperature on the living cationic polymerization of 2-phenyl-2-oxazoline explored utilizing an automated synthesizer. Macromol Rapid Commun 25 339-343... 

The temperature optimization for the RAFT polymerization of EAA revealed an optimum reaction temperature of 70 °C. Block copolymers with a poly(methyl acrylate) (PMA), a poly(n-butyl acrylate) (PnBA), a PMMA, or a poly(A,A-dimethyl aminoethyl methacrylate) (PDMAEMA) first block and a poly(l-ethoxyethyl acrylate) (PEEA) second block were successfully synthesized in an automated synthesizer. The synthesis robot was employed for the preparation of 16 block copolymers consisting of 25 units of the first block composed of PMA (exp. 1 ), PnBA (exp. 5-8), PMMA (exp. 9-13), and PDMAEMA (exp. 13-16) and a second block of PEEA consisting of 25, 50, 75, or 100 units, respectively. The first blocks were polymerized for 3 h and a sample from each reaction was withdrawn for SEC analysis. Subsequently, EAA was added and the reactions were continued for 12 h. The molar masses and PDI values of the obtained block copolymers are shown in Fig. 15. 

The split-and-pool synthesis not only simplifies the complexity of the combinatorial synthetic process, but also offers additional important benefits. To undertake a full range of solid-phase chemical reactions, elaborate reaction conditions are needed for some chemical transformations. These include, but are not limited to, low temperature and inert atmosphere conditions. Parallel synthesis of a thousand compounds requires handling of a thousand reaction vessels. The timely addition of sensitive reagents (e.g., butyl lithium) at low temperature (—78°) under inert atmosphere during parallel synthesis is not a trivial task. It can be done if sophisticated automated synthesizer equipment is designed to handle and tolerate such reaction conditions. Such a synthesis can alternatively be performed easily in a manual fashion using a split-and-pool method that requires only a limited number of reaction vessels. Examples from Nicolaou s17 and Schrei-ber s18,19 laboratories have shown that the split-and-pool method is the methodology of choice for the synthesis of complex and diversity-oriented combinatorial libraries. 

For the fast identification of lead compounds for novel, small molecule enzyme inhibitors or other ligands for proteins, the screening of large and diverse arrays of compounds prepared on insoluble supports is one of the most efficient approaches.1-8 Parallel solid-phase synthesis has been found to be particularly well suited for the preparation of such arrays of diverse compounds since multistep synthetic sequences on insoluble supports can be conducted on fully automated synthesizers. 

C-E bond formation via hydroalumination, 10, 859 C-E bond formation via hydroboration, 10, 842 olefin cross-metathesis, 11, 195 terminal acetylene silylformylation, 11, 478 Chemspeed automated synthesizer, for high-throughput catalyst preparation, 1, 356 Chini complexes, characteristics, 8, 410 Chiral bisphosphanes, in hydrogenations on DIOP modification, 10, 7... 

Nucleic acids are synthesized chemically in laboratories around the world using automated synthesizers. Therefore, if one can prepare a phosphor-amidite of a spin-labeled nucleoside, which is the building block for... 

Abarelix was synthesized by the solid phase method using an automated synthesizer (e.g. Beckman Model 990). The amino acid residues used can be purchased from commercial sources (e.g. Aldrich Chemical Co., Milwaukee, Wis.), or can be produced from commercially available starting materials according to known methods. Amino acids which are not obtained commercially can be synthesized in a protected form for coupling, or, if appropriate, can be coupled to form a peptide and subsequently modified to the desired form. 

At this point it may be mentioned that the use of different protecting group strategies has recently enabled numerous linkers to be synthesized [10], and automated syntheses of longer oligosaccharides performed [11]. 

The presence of an equatorially substituted cyclic sulfonium intermediate 7 that controls the stereoselectivity of glycosylation was confirmed by nuclear magnetic resonance (NMR) spectroscopy. Combined use of this methodology to introduce a-glycosides and traditional /3-glycoside protocols provides a potential route to one-pot multistep glycosylations and automated syntheses for a wide variety of oligosaccharides. 

This material 9 was then placed in the 40 reactors of an automated synthesizer... 

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