 |
||
 |
 |
 |
 |
||
 |
||
Coupling Agent T3P: An interesting non-toxic and economical alternative
A lot of interesting chemical entities contain amide moieties. Peptides are the most well-known ones. Peptide chemistry is well developed and these interesting molecules can be even produced in computerized reactor set-ups, where protection, coupling and deprotection is part of the chemical transformations applied. The common approach is to start with a N-protected aminoacid. The COOH end-part of the aminoacid is transformed to an active ester using, for instance, dicyclohexylcarbodiimide (DCC) and 1-hydroxybenzotriazole (HOBt), whereupon this intermediate is reacted with an unprotected aminoacid, yielding a dipeptide. The product is isolated and the sequence is repeated to generate a tripeptide and so-forth. A lot of coupling agents [EDC; HOBt, HATU; TBTU; HBTU; BOP] are commercially available on the market and are used in several applications. However, these reagents are not only rather toxic but also expensive. 1 Propanephosphonic acid anhydride (T3P) as a solution in N,N-dimethylformamide (DMF) and tetrahydrofuran (THF) was brought to the market as a water trapping agent and is available from laboratory reagent suppliers such as Aldrich. It was discovered that it had a lot of interesting chemical properties. One of which is its suitability as a coupling agent to generate amides from acids and amines.
Upon CMLE’s request, Archimica GmbH 2 supplied this material in a special solvent, being 2-methyltetrahydrofuran (2MeTHF), a fantastic solvent hardly miscible with water and a solvent that is not lost to the aqueous phase during work-up, in contrast when working with either THF or DMF. In the reaction tested, a complex benzoic acid derivative was treated with T3P in 2MeTHF followed by the addition of a complex secondary amine. The in-house developed process was performed successfully at 250L scale. 1 http://www.chempep.com 2 50%wt T3P solution in 2MeTHF available from Archimica GmbH. For additional information it is possible to consult the Archimica web-site: http://www.archimica.com. Back to Winter 2010 Newsletter
|
||
|
||
 |
||
