The domino blocks: A simple solution for parallel solid-phase organic synthesis

Bioorganic and Medicinal Chemistry Letters

Volumn 8, Issue 22, 1998, Pages 3261-3264

  Krchňák, Viktor ^a,b   Paděra, Víteček ^b  

^a SIDDCO   (United States)

^b Torviq   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ARTICLE; CHEMICAL REACTION; DEVICE; LABORATORY AUTOMATION; SOLID PHASE EXTRACTION; SYNTHESIS;

EID: 0032542074     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(98)00594-0     Document Type: Article

References (14)

1. 1. Lam, K. S.; Lebl, M.; Krchňák, V. Chem. Rev. 1997, 97, 411. Nefzi, A.; Ostresh, J. M.; Houghten, R. A. Chem. Rev. 1997, 97, 449.
2. 1. Lam, K. S.; Lebl, M.; Krchňák, V. Chem. Rev. 1997, 97, 411. Nefzi, A.; Ostresh, J. M.; Houghten, R. A. Chem. Rev. 1997, 97, 449.
3. 2. Houghten, R. A. Proc. Natl. Acad. Sci. U.S.A. 1985, 82, 5131.
4. 3. Krchňák, V.; Vágner, J. Peptide Res. 1990, 3, 182.
5. 4. The MultiBlock is commercially available from CSPS, San Diego, CA (http://www.5z.com).
6. 5. For recent overview of automation/integration of SPOS see e.g. by Cargill, J. F.; Lebl, M. Curr.Opin.Chem.Biol. 1997, 1, 67.
7. 6. Description of the domino block: The domino block (Torviq, Tucson AZ) is Teflon made liquid distribution manifold (footprint of a microplate) that has two functions: (i) to clamp reaction vessels and (ii) to connect all reaction vessels to one common port. This common port was used to introduce and to remove a liquid. Plastic polypropylene syringes equipped with a porous disk at the bottom were used as reaction vessels. The syringes were attached via a male Luer fitting to the liquid distribution manifold arrayed with a female Luer lock fittings. We constructed blocks for 12 (4 rows of 3 syringes) and 24 (6 rows of 4 syringes) reaction vessels. The first block accommodated syringe size up to 20 mL; the 24-block was useful for 2.5 and 5-mL syringes.
8. 7. Description of operation: the common port of the distribution valve was connected to the port A to connect the domino block with reaction vessels to an evacuated waste container (Figure 2). After the syringes were emptied, which typically took less than 10 sec, the valve was turned to the port C for a fraction of a second. A small amount of air/inert gas was introduced into syringes via this port equipped with a syringe filter. Then the valve was turned to the port B to connect the domino block with the solvent container. The vacuum created inside reaction vessels drawn the liquid into the vessels. We also used an alternative way of introducing an air gap into syringes. After the syringes were evacuated, the valve was directly switched to the port B. The common port of the valve was then connected to the port C, which introduced the air, before the syringes were completely filled with the solvent. This washing operation was repeated as many times as washes were required. One washing liquid was used in the above-described configuration. For a comfortable selection of washing solvents a distribution valve can be inserted between the 4-port valve and solvent reservoirs.
9. 8. Radiofrequency tagged T-bag-like reaction vessels were described by Moran, E. J.; Sarshar, S.; Cargill, J. F.; Shahbaz, M. M.; Lio, A.; Mjalli, A. M. M.; Armstrong, R. W. J. Am. Chem. Soc. 1995, 117, 10787. Nicolaou, K. C.; Xiao, X. Y.; Parandoosh, Z.; Senyei, A.; Nova, M. P. Angew. Chem. Int. Ed. 1995, 34, 2289.
10. 8. Radiofrequency tagged T-bag-like reaction vessels were described by Moran, E. J.; Sarshar, S.; Cargill, J. F.; Shahbaz, M. M.; Lio, A.; Mjalli, A. M. M.; Armstrong, R. W. J. Am. Chem. Soc. 1995, 117, 10787. Nicolaou, K. C.; Xiao, X. Y.; Parandoosh, Z.; Senyei, A.; Nova, M. P. Angew. Chem. Int. Ed. 1995, 34, 2289.
11. 9. Krchňák, V.; Weichsel, A. S.; Cabel, D.; Flegelova, Z.; Lebl, M. Mol. Diversity 1996, 1, 149.
12. 11 Twelve different alcohols were distributed into the wells, one per each column (methanol, ethanol, 2-propanol, allyl alcohol, 1,3-propanediol, 1-(2-hydroxyethyl)pyrrolidine, 1-piperidineethanol, 1-(2-hydroxyethyl)-2-pyrrolidinone, benzyl alcohol, 4-chlorbenzylalcohol, 4-nitrobenzylalcohol, and phenethylalcohol). After an overnight reaction and washing with DMF and MeOH the products were cleaved by 0.5 M NaOH and extracted into 50 % MeOH in water.
13. 11. Krchňák, V.; Weichsel, A. S.; Lebl, M.; Felder, S. Bioorg. Med. Chem. Lett. 1997, 7, 1013.
14. 12. Lebl, M.; Krchňák,V. Solid Phase Synthesis & Combinatorial Chemical Libraries; Epton, R., Ed.; Mayflower Scientific Limited, Birmingham, 1998.