The OntoBLOCK system

The OntoBLOCK system [10] is a fully automated synthesis-analysis platform. A set 

Extensive washing of the resin with a series of appropriate solvents removes excess reactants and impurities from the solid support after each chemical step (Fig. 5). This task is carried out very efficiently by an automated wash station which utilizes two arrays of 48 luer lock needles to simultaneously add solvent to a set of alpha-beta reaction blocks. Microsoft Windows -based control software provides a custom-designed wash profile for each combinatorial experiment. This profile specifies the identity, volume, order and delivery speed of each wash solvent, as well as the agitation speed and time between solventdeliveries. 

Once the final compound has been cleaved from the solid support, the contents of the blocks are drained into a standard 96-well microtiter plate. The solvent is removed in a vacuum oven and appropriate daughter plates (master chemistry plate, master biology plate and analytical plate) are prepared using a 96-channel pipetting robot. The average production capacity of such a work station is between 1000 and 2000 single spatially dispersed compounds per day. 

---

Fig. 5. The OntoBLOCK system synthesis, analysis and archival strategy.

Scheme 4. Examples of libraries synthesized using the OntoBLOCK system.

Ontogen has also automated the synthesis of a variety of heterocyclic pharmacophores [14] (Scheme 4) using the OntoBLOCK system. 

Workers at Ontogen [82,83] reported the use of the OntoBLOCK system which utilizes a Tecan robot. They have implemented this technology for solid-phase synthesis to generate over 50 000 compounds corresponding to libraries of pyrroles, phosphonates, phosphinates, lactams, imidazoles, hydantoin imides and thioimides, oxazoles, and b-lac-tams. These libraries have resulted in potent and selective inhibitors of iNOS, PTPases and cdc25 phosphatase and compounds that reverse the P-glycoprotein (Pgp)-based multiple drug resistance (MDR) phenomenon in cellular assays and in animal models [98],... 

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. 

---