New technique for high-throughput synthsis Bioorgan

Abstract. A new technique for high throughput solid phase synthesis using the centrifuge based liquid removal from readily available standard microtiterplates is described. This technique eliminates the filtration step and is therefore applicable to simultaneous processing of an unlimited number of reaction compartments. Its application is illustrated on the synthesis of an array of 380 tetrahydroisoquinolinones. © 1999 Elsevier Science Ltd. All rights reserved. The arrival of combinatorial techniques (for reviews see ref. 1) stimulated the interest in new methods for the automation of synthetic processes. The scientific community is waiting for an instrument that would be rather simple, therefore inexpensive, and would allow each chemist to synthesize 100 -1000 compounds in a batch. This instrument would be used for the deconvolution of active compound from biologically active mixtures, or for compound optimization, so called "lead explosion". One of the basic problems of solid-phase synthesis automation is the separation of liquid and solid phases. All known automatic solid-phase synthesizers utilize filtration as the principle for separation of solid and liquid phase (for reviews see ref. 2). However, filtration always brings the danger of the filter clogging, which is especially harmful in the case of multiple synthesizers. We have tested the principle of "surface suction" for removal of supernatant from the sedimented suspension of solid-phase particles. 3'4 We have successfully designed and built the separation station for 96-well plates and applied this principle to our robotic synthesizer in which up to 72 plates can be processed simultaneously. 3 Even though powerful, the surface suction does not allow processing an unlimited number of reaction vessels simultaneously -the number of processed vessels depends on the number of needles performing the suction. The simpler way for the simultaneous processing of hundreds of reaction vessels is based on a different technique, which we call "tilted centrifugation". 5 The principle of tilted centrifugation is illustrated i

Observation of a conformational effect in peptide molecule by reversed-phase high-performance liquid chromatography

ABSTRACT RP-HPLC of analogues of oxytocib containing a reduced peptide bond was studied using various columns and buffers. Anomalous behavior of one analogue served as a basis for the discussion of possible conformational consequences of this substitution

New approach for preparation of 2,3,7-trisubstituted 3,4-dihydroisoquinolinone libraries on solid phase

Summary In an attempt to prepare 7-substituted 3,4-dihydroisoquinolinone family of compounds, we observed an unexpected decarboxylation. The reaction of 4-nitrohomophthalic anhydride with a Schiff base formed on solid support leads to the formation of core structure. LC-MS and 1 H NMR analysis confirmed the structure of unexpected intermediate. A library of 38,400 compounds was produced using this new synthetic approach

From Merrifield to MetaPhore: A Random Walk with Serendipity Garland R. Marshall

Introduction It is the highpoint of my career to receive this award, named in honor of my Ph.D. mentor, Bruce Merrifield. There is little that I can add to what we all know regarding the impact that Bruce has had on peptide research. Certainly, he has had a more significant impact on my scientific development than any other individual. I do need, however, to acknowledge from the start that I have made a habit of associating myself with outstanding individuals, such as Bruce, who have made me look good. My mother always advised, "You are known by your friends" and I took those words to heart. I also need to acknowledge the support of my wife Suzanne, our four children and their spouses for their sacrifices and encouragement over the many years. Suzanne and I are in the middle of our 42nd year of marriage. She received a Ph.T. (put husband through) degree from Caltech when I graduated in 1962, and has never wavered in her support. So my thanks to my family, students, postdocs and colla