Robot synthesis

The protocol offers a direct and efficient method for the synthesis of the boronic ester in the solid phase, which hitherto met with little success using classical methodology (Scheme 1-42). A solid-phase boronate (113 [155], 114 [156]) is quantitatively obtained by treating a polymer-bound iodoarene with the diboron (82). The subsequent coupling with haloarenes furnishes various biaryls. The robot synthesis or the parallel synthesis on the surface of resin is the topic of further accounts of the research. 

While NMR spectra possess a high information content, this confers a level of complexity that can be obstructive if a quick and simple answer is required. The use of NMR flow probes has reduced the time taken to acquire a spectrum to 2-3 min and flow NMR has consequently found considerable application in robot synthesis, multiple parallel synthesis (MPS) or combinatorial chemistry. Since H possesses 5600 times the receptivity of it is inevitable that it will continue to be the nucleus of choice in this area, complicating the analysis. Unless automatic analysis is able to transcend the aid to interpretation role and into the confirm or refute the structure role, the higher information content of the NMR spectrum constitutes a threat rather than an opportunity. 

An important feature is that, with the exception of the catalyst synthesis, this is a fully automated process. Indeed, we envisage that in industry the entire process, including the synthesis and testing, can be automated using commercially available synthesis robots. If robotic synthesis and screening is available, the size of the test sets can be increased. Moreover, it is precisely the automated modelling and analysis aspect that is lacking in the robotic laboratory workflow. 

Brooking, P., Crawshaw, M., Hird, N. W., et al. (1999) The development of a solid-phase tsuge reaction and its application in high throughput robotic synthesis. Synthesis 11, 1986-1992. 

Boutin JA, Hennig P, Lambert PH, Bertin S, Petit L, Mahiev JP, Serkiz B, Volland JP, Fauchere JL, Combinatorial peptide libraries Robotic synthesis and analysis by nuclear magnetic resonance, mass spectrometry, tandem mass spectrometry, and high-performance capillary electophoresis techniques, Anal. Biochem., 234 126-141, 1996. 

J Boutin, P Henning, P Lambert, S Berlin, L Petit, J-P Mahieu, B Serkiz, J-P Volland, JL Fauchere. Combinatorial peptide libraries robotic synthesis and analysis by NMR, mass spectometry, tandem mass spectrometry and high-performance capillary electophoresis techniques. Anal Biochem 234 126-141,... 

RN Zuckermann, JM Kerr, MA Siani, SC Banville, DV Santi. Identification of highest-affinity ligands by affinity selections from equimolar peptide mixtures generated by robotic synthesis. Proc Natl Acad Sci USA 89 4505-4509, 1992. 

Profile This privately held company was founded in 1993 to integrate advanced technologies in structure-based design, combinatorial chemistry, and chemi-informatics for the cost-effective discovery of orally active pharmaceuticals. The company has developed a system capable of generating new drugs through computer-controlled robotic synthesis and analysis of chemical libraries. Current drug discovery efforts are focused on cardiovascular disease and cancer. 

B. Volland, J.P f auchbre, J.L. Combinatorial Peptide Libraries Robotic Synthesis and Analysis by Nuclear Magnetic Resonance, Mass Spectrometry, Tandem Mass Spectrometry, and High-performance Capillary Electrophoresis Techniques, AnflZ. Biochem. 234, 126-141 (1996). 

JA Boutin, P Hennig, P-H Lambert, et al. Combinatorial peptide libraries robotic synthesis and analysis by nuclear magnetic resonance, mass spectrometry, tandem... 

Subsequent coupling with iodo- or bromoarenes, followed by hydrolysis with trifluoroacetic acid, furnishes various biaryls. The robot synthesis or parallel synthesis on the surface of resin will be the topic of further accounts of this research. 

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