Books
in black and white
Main menu
Home About us Share a book
Books
Biology Business Chemistry Computers Culture Economics Fiction Games Guide History Management Mathematical Medicine Mental Fitnes Physics Psychology Scince Sport Technics
Ads

Solid-phase organik syntheses - Burdges K.

Burdges K. Solid-phase organik syntheses - John Wiley & Sons, 2000. - 283 p.
ISBN 0-471-22824-9
Download (direct link): phaseorganicsynthesis2000.pdf
Previous << 1 .. 57 58 59 60 61 62 < 63 > 64 65 66 67 68 69 .. 82 >> Next

81. Deegan, T. L.; Gooding, O. W.; Baudart, S.; Porco, J. A., Jr. Non-Acidic Cleavage of Wang-Derived Ethers from Solid Support: Utilization of a Mixed-Bed Scavenger for DDQ, Tetrahedron Lett. 1997, 38, 4973.
82. Rueter, J. K.; Nortey, S. O.; Baxter, E. W.; Leo, G. C.; Reitz, A. B. Arylsul-fonate Esters in Solid Phase Organic Synthesis. I. Cleavage with Amines, Thiolate, and Imidazole, Tetrahedron Lett. 1998, 39, 975.
83. Gayo, L. Ì.; Suto, M. J. Traceless Linker: Oxidative Activation and Displacement of a Sulfur-Based Linker, Tetrahedron Lett. 1997, 38, 211.
84. Parlow, J. J. Simultaneous Multistep Synthesis Using Polymeric Reagents, Tetrahedron Lett. 1995, 36, 1395.
85. Sim, Ì. Ì.; Lee, C. L.; Ganesan, A. Combinatorial Synthesis of 2-Thioxo-4-dihydropyrimidinones, J. Org. Chem. 1997, 62, 9358.
86. Kulkarni, B. A.; Ganesan, A. Solution-Phase Combinatorial Synthesis of 4-Hydroxyquinolin-2(l#)-ones, Chem. Commun. 1998, 785.
Solid-Phase Organic Synthesis. Edited by Kevin Burgess Copyright © 2000 John Wiley & Sons, Inc. ISBNs: 0-471-31825-6 (Hardback); 0-471-22824-9 (Electronic)
CHAPTER 6
SOLID-PHASE ORGANIC SYNTHESIS ON RADIATION-GRAFTED POLYMER SURFACES: APPLICATION OF SYNPHASE CROWNS TO MULTIPLE PARALLEL SYNTHESES
intermediate --------------> product
pin pin
IAN W. JAMES, GEOFFREY WICKHAM, NICHOLAS J. EDE, and ANDREW M. BRAY Chiron Technologies Pty. Ltd.
6.1. MULTIPLE PARALLEL SYNTHESES OF INDIVIDUAL COMPOUNDS
6.1.1. Introduction
After a few frenzied years of development in combinatorial chemistry, there is now a clearly identifiable trend away from the synthesis of complex
195
196 SOLID-PHASE ORGANIC SYNTHESIS ON RADIATION-GRAFTED POLYMER SURFACES
mixtures/pools of compounds toward multiple parallel syntheses of individual compounds. This trend has been established largely to circumvent the time-consuming process of “deconvolving” compound mixtures to identify biologically active components and, also, to avoid the problem of “false positives.” Using high-throughput chromatographic and structural analyses, for example, HPLC, electrospray mass spectrometry (ESMS), and even NMR spectroscopy, it is now possible to analyze libraries of hundreds to thousands of individual compounds to establish the purity and structural integrity of the libraries’ constituents. This information is essential for determining which reaction products are suitable for biological screening. Solid-phase organic synthesis continues to be a popular method for preparation of libraries,1 although solution-phase methods are also used.2 Syntheses of compounds on discrete units of solid-phase material, such as SynPhase crowns,1,3 simplify handling issues associated with multiple parallel syntheses. These units of solid support can be “tagged” electronically for identification purposes or placed in particular spatial patterns, for example, 8 x 12-array formats, as in the case of the Multipin method (Figure 6.1). An important advantage of both of these parallel synthesis techniques
Figure 6.1. Block of 96 l-series crowns being washed in a polypropylene bath containing organic solvent.
6.1. MULTIPLE PARALLEL SYNTHESES OF INDIVIDUAL COMPOUNDS 197
is the ability to track individual reactions facilitating identification of expected structures on each SynPhase crown.
6.1.2. Radiation-Grafted Polymer Surfaces
Most solid-phase organic syntheses described in the literature have been performed on beaded cross-linked polystyrene resin.4 A small, though growing volume of published work has been performed on radiation-grafted polymer surfaces, such as SynPhase crowns. Radiation-grafted polymers were first used for peptide synthesis in the early 1980s.1,5,6 Following many years of development, the graft polymers now available on SynPhase crowns include polystyrene3 and a hydrophilic copolymer of methacrylic acid and dimethylacrylamide,3 both of which can be used for solid-phase organic synthesis. Although dissimilar in appearance, radiation-grafted polymer surfaces have a number of physical properties that are similar to resins from a synthetic perspective. In both cases, synthesis takes place within a solvated cross-linked polymer gel. Unlike cross-linked resins, the graft polymer is anchored to a rigid base polymer unit (Figure 6.2), which could be presented in a number of formats: for example, as films or injection-molded items. In the case of the SynPhase crowns, the base polymer is injection molded as a small rigid finned device with a moderately large surface-to-volume ratio.7,8 The shape and size of the base polymer can be varied to control loading. For example, at the time of writing, the polystyrene-grafted, I-series SynPhase crown could be produced with loadings up to 35 jimol on a device that is 20 mm long and up to 6 mm in diameter.
The advantages of SynPhase crowns over conventional solid-phase syntheses on resin beads are as follows:
Previous << 1 .. 57 58 59 60 61 62 < 63 > 64 65 66 67 68 69 .. 82 >> Next