Multipin synthesis

Chiron Technologies specializes in multiple parallel synthesis. Its Multipin Synthesis Technology was developed and patented by Chiron Mimotopes and is used by Chiron Corporation and the University of California at Berkeley, among... 

Ede NJ, Bray AM. A simple linker for the attachment of aldehydes to the solid phase. Application to solid phase synthesis by the Multipin method. Tetrahedron Lett 1997 38 7119-7122. 

Maeji, N. J. Valerio, R. M. Bray, A. M. Campbell, R. A. Geysen, H. M. Grafted Supports Used with the Multipin Method of Peptide Synthesis, Reactive Polymers 1994, 22, 203. 

Ede, N. J. Bray, A. M. A Simple Linker for the Attachment of Aldehydes to the Solid Phase. Application to Solid Phase Synthesis by the Multipin Method, Tetrahedron Lett. 1997, 38, 7119. 

Linear polystyrene can be generated on insoluble polymers by /-irradiation of the latter in a solution of styrene [110]. Polystyrene grafted onto polytetrafluoroethylene [111-116], polyethylene [2,110,117], or polypropylene [15] can be functionalized in the same way as cross-linked polystyrene, and loadings of up to 1.0 mmol/g can be attained. These supports, which are also available as crown-shaped pins (Multipin, 2-3 mm diameter, 8-10 pmol per crown), have been used for the synthesis of peptides [2,110,111,118], oligonucleotides [112-115,117,119], and small molecules [120-122]. 

Polyethylene has been grafted with acrylic acid, 2-hydroxyethyl methacrylate//V,/V-dimethylacrylamide, or methacrylic acid//V,/V-dimethylacrylamide to yield supports (e.g. Figure 2.10) suitable for the synthesis of peptides [2,222-224] and other compounds [216,225,226]. A similar support, also suitable for the synthesis of peptides, is polypropylene grafted with hydroxypropyl acrylate [227]. These supports can be used as membranes or as crown-shaped pinheads (Multipin 2-4 mm diameter) with loadings of 1.2-2.2 pmol per crown. 

Scheme 1. Multipin SPOC synthesis of peptoid libraries.

Recent literature contains a multitude of examples of synthetic organic methodologies which have been optimized and applied to the solid-phase synthesis of combinatorial libraries [2]. In fact, the production of a number of these libraries has been realized on such systems as the Multipin SPOC [8], the DIVERSOMER [9] and the OntoBLOCK [10], All three apparatuses allow the automated production of spatially dispersed combinatorial libraries and facilitate the isolation, identification, screening and archiving of single compounds in distinct physical locations which are crucial factors during lead discovery and optimization. 

Using the Multipin SPOC systems, researchers at Chiron have demonstrated the automated solid-phase synthesis of peptoids 1 (Scheme 1) [12], while Ellman and co-workers have completed the synthesis of a combinatorial library of 11 200 spatially dispersed benzodiazepines 2 (Scheme 2) [13],... 

Bray AM, Jhingran AG, Valerio RM, Maeji NJ, Simultaneous multiple synthesis of peptide amides by multipin method. Application of vapor-phase ammonolysis, J. Org. Chem., 59 2197-2203, 1994. 

A useful vapor-phase ammonolysis has been developed for simultaneous multiple synthesis of peptide amides by both the resin and multipin methods. Pins or peptide-resins are deprotected and washed with CHjCb, DMF, and CH2CI2, and are then air-dried. A bottle of NH3/THF (3 7 v/v, 50-100 mL) was cooled to —78 °C and placed in a well-greased desiccator together with the multipin pin holders (1-4) or the open vials containing resins (130mg/vial). The desiccator was clamped shut, partially evacuated (10 s), and then left to stand at 20°C for 24 h. After this time, the multipin pin holders and the resins were removed from the dessicator and allowed to stand for 30 min. Qeaved peptides were eluted from the pins by immersing them in MeCN/H20 (4 6) for 3 h, or from the resins by washing with AcOH/MeCN/HjO (3 4 3, 5 x ImL). 

Takahashi, T Ebata, S. Doi, T. Solid Phase Approach to Muscone Synthesis Rh(I)-Catalysed Hydroformylation of a 1,1-Disubstituted Alkene on the Multipin Sysitm, Tetrahedron Lett. 1998,59, 1369. 

NJMaeji, AM Bray, RM Valerio, W Wang. Larger scale multipin peptide synthesis. Peptide Res 8 33-38, 1995. 

RM Valerio, AM Bray, RA Campbell, A Dipasquale, C Margellis, S. J. Rodda, FtM Geysen, NJ Maeji. Multipin peptide synthesis at the micromole scale using 2-hydroxyethyl methacrylate grafted polyethylene supports. Int J Peptide. Protein Res 42 1-9, 1993. 

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