MULTIBLOCK - User's Manual

Manual Multiple/Library Synthesizer

Quick overview:

The instrument was designed by Krchnak and Vagner for laboratories with high demand for synthetic output and low budget. MULTIBLOCK is constructed from Teflon, polypropylene, glass, and stainless steel. Reactors equipped with plastic frits are either stoppered on both ends by flexibly mounted multistoppers (for coupling) or the whole block of reactors is placed on a suction table and all reactors are washed simultaneously. After placement of MULTIBLOCK onto the multistopper, coupling reagents are added, the upper multistopper is attached and the assembly is placed onto a shaker, or it is shaken only occasionally by hand. Each reactor can hold up to 2ml of swollen resin, i.e. 0.4g. However, we recommend to use maximally 1ml (0.2g). This means that 0.04 to 0.2 mmol of 42 different compounds can be synthesized in all reactors (depending on the resin substitution). The use of various coupling reagents, resins, protecting groups in the same run of multistep synthesis is possible. Reactions can be performed in an ultrasonic bath (Vagner, J., Kocna, P., Krchnak, V.: Peptide Res. 4, 284 (1991)). MULTIBLOCK design is optimal for noninvasive continuous monitoring of amide bond formation (Krchnak, V., et al. IJPPR 32, 415 (1988)). The synthesizer consists of five parts:
  1. A teflon block that holds 42 reactors, polypropylene syringes equipped with a plastic frit (Krchnak, V., Vagner J.; Peptide Res. 3, 182 (1990))
  2. A vacuum adaptor that connects each reactor to vacuum line and allows rapid washing of resin under continuous-flow
  3. Two teflon plates with 42 stoppers to which the teflon block is attached during deprotection or condensation reactions
  4. A glass cover to allow mixing of resin for randomization.
Extra components of the system are:
  1. Washing attachment
  2. Replacement reaction vessels (reactors)
  3. Test tube holders


Library synthesis:

The only change in this procedure for library preparation is the randomization step. This step can also be used for uniform distribution of the resin at the beginning of synthesis. The resin can be colorized by bromophenol blue for better visualization (or for monitoring of amide bond formation).

All other steps are identical to the multiple synthesis described earlier.

Deprotection by trifluoroacetic acid and its mixtures:

We recommend performing cleavage in the MULTIBLOCK with the following method:

  1. Wash the reactors with dichloromethane.
  2. Place the block on the lower multistopper and make sure that it will not leak.
  3. Add mixture K (or other cleavage reagent).
  4. Wait for several minutes until the development of gases is finished (if any).
  5. Attach upper multistopper and place the block on the shaker. Trifluoroacetic acid mixtures are very difficult to seal tightly and therefore we recommend shaking in vertical position with occasional manual shaking.
  6. Open and lift the upper multistopper for several seconds to release any pressure that may have built up.
  7. Replace the upper multistopper and while pressing it hard against the upper lip of the block (hold it on the sides with both hands) lift the block from the lower multistopper and transfer it on top of a grid built from a set of containers which will receive the released compounds (e.g., test tubes) that have been carefully arranged in a geometry matching the arrangement of the tips of each reaction vessel. Test tube rack made of foam polypropylene is available from CSPS.
  8. Lift the upper multistopper and let the liquid flow out of the columns.
  9. Washing of the resin can be done by simple elution with an extraction solvent or by transferring the block onto the lower multistopper, adding a solvent, closing it with the upper multistopper and shaking.

Important points for successful use of the MULTIBLOCK:

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Last Modified: Thursday, January 07, 2010
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