Solid-phase synthesis reactors

CSPS Multiblock J-Kem Solid-Phase Synthesis Reactor J-Kem Solid-Phase Synthesis Reactor Micro... 

Reactor 36 [R 36] Solid-phase Synthesis-Pneumatic Agitation-8-Reactor System... 

Figure 4.35 Schematic of the solid-phase synthesis-pneumatic agitation-8-reactor system [75].

Various techniques have been developed that enable the rapid preparation and screening of large numbers of different compounds by parallel solid-phase synthesis. Reactions can, for instance, be conducted in an array of reactors such as that sketched in Figure 1.1. Synthesizers with up to approximately 600 discrete reactors are commercially available these enable the automated preparation of compound libraries containing up to 0.1 mmol of each compound. Discrete reactors are also well suited for the development and optimization of solid-phase chemistry. 

Solid-phase chemistry can readily be automated, and is therefore well suited to parallel, high-throughput compound production. Programmable synthesizers with hundreds of reactors for solid-phase synthesis have become commercially available these enable the production of large arrays of compounds (one different compound per reactor). This is usually achieved by performing the same synthesis in each reactor, but using different reagents. 

A recent article describes the construction and use of a parallel polypropylene reactor comprising of cylindrical, expandable reaction vessels with porous frits at the bottom (Fig. 7.4)21. This is the first description of reaction vessels for microwave-assisted synthesis that may be useful for carrying out solid-phase synthesis using bottom filtration techniques in conjunction with microwave heating. However, at the time when tins chapter was being written no application of this system for solid-phase synthesis had been reported. 

Workers at Parke-Davis reported the DIVERSOMER method in 1993 [63,64] which utilized proprietary reactors in combination with a Tecan robot. This technology has been implemented to generate libraries ofhydantoins [63-66,95], benzodiazepines [63-66, 95], and quinolones [67,96,97] by solid-phase synthesis. 

Yan, Y., U.T. Bornscheuer, G. Stadler, M. Reuss, and R.D. Schmid, Lipase-Catalyzed Solid-Phase Synthesis of Sugar Fatty Acid Esters in a Stirred-Tank Membrane Reactor, J. Am. Oil Chem. Soc. in press (2000). 

Simmons-Smith cyclopropanation, 456 Simmons-Smith reaction, 455 six-centered transition state, 264 Smiles-type rearrangement, 7 SOCI2, 19, 159 sodium azide, 365, 375 sodium borohydride, 416 sodium hexamethyldisilazide, 290 sodium hydride, 372, 375. 383 sodium in liquid ammonia, 440 sodium iodide, 379 sodium phenylselenide, 458 sodium trifluoroethoxide, 447 solid phase synthesis, 25 Sonogashira conditions, 409 Sonogashira coupling, 411 spartadienedione, 144 spontaneous csdodimerization, 23 S-shaped and C-shaped diastereomers, 83 stainless steel reactor, 283... 

The characteristics of the supports used in solid-phase synthesis are very important for automated synthesis. Supports that are mechanically unstable and tend to fracture and produce fine particles can either clog frit material in the reactor or pass through the frit material and clog fluidic lines... 

Large-scale solid phase synthesis of peptides can be performed on the lloor-standing ACT Model 400 batch system (Figure 5) that operates in a single reactor mode with 0.1-5 kg of starting solid support (36). All operations and... 

MultiBlock. In the late eighties, Krchnak and Vagner designed the MultiBlock, the first reaction block for parallel solid-phase synthesis (Figm-e 3.19). The MultiBlock consists of five parts (i) a Teflon block that holds 42 reactors, polypropylene syringes equipped with a plastic (ii) a vacuum adapter that connects each reactor to a vacuum line and allows... 

The explosion of combinatorial chemistry in the nineties triggered the constmction of a variety of reaction blocks for multiple parallel synthesis. Some of them are still in production, including the MiniBlock developed by Bohdan, Inc. (now part of Mettler-Toledo, www.mt.com/autochem) and Solid-Phase Synthesis Reaction blocks by J-KEM (www.jkem.com). The Bohdan MiniBlock reactor can hold up to 48 disposable polypropylene-fritted tubes in a 48-well format (6x8 array) and accommodates IRORI s MicroKans. The MiniBlock can be equipped with accessories for synthesis under inert atmosphere or at elevated temperatures. 

Myers Squibb, New York, NY). Since its isolation, the complexity of pachtaxel s structure made it irresistible as a target for total synthesis. For example, syntheses have been published by Nicolaou et al., " Holton et al., and others. ° Solid-phase synthesis has been used in the context of combinatorial derivatization of the resin-bound paclitaxel skeleton to provide analogs for structure activity relationship (SAR) studies. For example, Xiao et al. and Nicolaou et al. attached paclitaxel core 181, previously accessed from baccatin III, to chlorotrityl resin 182 to give 183 (Scheme 3.34). ° Resin 183 was divided among 400 MicroKan reactors, and the Fmoc group was then removed... 

Polypropylene syringe reactors for solid-phase synthesis (pore size 25 tm) (Fig. 3). 

Fig. 3 Glass reactor and syringe reactor employed for solid-phase synthesis on an orbital shaker...

Prepare a cartridge of alumina by filling a syringe reactor for solid-phase synthesis with a 2-3 cm layer of alumina, and filter the solution through this cartridge. 

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