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synthesis

Synthesis- Solid phase and solution phase synthesis have become an important part of the drug development process that is used in the pharmaceutical industry. These processes are used to generate the compound libraries that are used for high-throughput screening.

Applications

  • Solid phase synthesis
  • Solution phase synthesis
  • Catalyst synthesis

The SOPHAS® platform represents a new generation of synthesizer for automated solid-phase and solution-phase synthesis, capable of hundreds of parallel syntheses in a single run. The SOPHAS has been extensively used for parallel solid phase synthesis, and is the platform that was used to develop the first fully-automated parallel solution phase synthesis ( Fully automated multi-step solution phase synthesis using polymer supported reagents: preparation of histone deacetylase inhibitors, E. Vickerstaffe, B. Warrington, M. Ladlow, and S. Ley, Org. Biomol. Chem., 2003, 1, 2419-2422).

Synthesis is performed using the unique DESYRE reaction blocks from Zinsser. These blocks are configured in the microplate footprint and have 96, 48, 24, or 8 reactors from 1 ml to 20 ml volume. The reactor blocks are machined from high-quality aluminum that provides the most efficient heat transfer.

desyre blocks

The Desyre block assembly consists of a carrier for the glass or plastic labware and a cover assembly that includes cross-slit septa for sealing of the block. This allows for an enclosed environment for temperature control while still allowing the probes to enter the vials.

desyre block

The user can decide on a lid assembly that best suits their needs. The lid assembly can include a gas inlet plate which traps a gas layer on the top area of the reaction vials to maintain inertness. The gas is delivered through a channel that is built into the Desyre block components.

desyre block

The Desyre block can also be configured for reflux with a second air flow path of cool air or nitrogen for the upper portion of the block. When combined with the special reflux vials (available in 7ml or 20ml) this will provide the temperature gradient necessary for a reflux operation.

desyre reflux

The Sophas can be configured for the addition of liquids or solids into the reaction vials. The real power lies in the ability to perform "filtration from the top". This is what makes unattended parallel synthesis possible, either solid phase or solution phase. This is accomplished using the unique tri-axial stainless steel probes. The 3-channel probe allows various combinations of liquid, gas and vacuum to be applied within the reaction vessel, and the mesh on the end of the center channel allows the filtration and washing that is required for synthesis "from the top".

filter probe

Click the next button on the animation below to see how this process works.

Another critical component for efficient reactions is the Zinsser Desyre vortexer. Many synthesis reactions fail or have low efficiency due to the action of inefficient mixers, which often produce a rotating motion that moves the liquid around but does not produce any mixing. The Desyre vortexers have been especially designed by Zinsser to overcome these limitations. These low noise, high speed mixers operate at 1,800 rpm and provide a unique directional movement that ensures efficient mixing. Multiple vortexers can be installed on the platform deck as either heaters (+150°C) or chillers (-40°C), and the robot gripper can move a complete assembled DeSyre reaction block to and from the vortexer positions.

vortexers

Zinsser also offers an "offline" vortexer station that allows long-term reactions to take place and freeing the automation platform for other tasks.

In addition to these custom tools for synthesis, the Sophas platform can be configured with any of the available automation tools from Zinsser, including automated weighing, capping/decapping, sonication, and more. FOr more information, please visit the Sophas web page and the Tools web page.

Photo gallery. Click these pictures to open a larger version in a new window.

sophas sophas sophas sophas
Large-deck Sophas connected to Lissy-TLC system
Sophas with special pipettor for viscous liquids
Compact Sophas for limited bench space
Sophas for catalyst synthesis
reactor pickup vortexers sophas software
The Desyre reactor lid can be automatically placed on the reactor, AND the entire reactor assembly can be moved by the robot
External vortexing station can be configured with heating or cooling vortexers as desired Moving a reactor block; deck has 2 heating and 1 cooling vortexer The Sophas can import methods from Excel or other formats; OR can be interfaced with Symyx Library Studio®
pasp
     
Steps for fully automated polymer-assisted solution phase synthesis      

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