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Solid Phase Synthesis

The solid phase synthesis plays an important role for the development of new compounds nowadays. During the search for such structures substance libraries are generated frequently and the single compounds are tested for their biological activity. The synthesis on solid support enables fast access to such libraries by the facile purification and easy handling. The constant demand for new compounds requires also a further development of the solid phase synthesis.

 

In our group the triazene-linkers T1 and T2 were developed.

The triazene group is stable against light, (atmospheric) oxygen, humidity, reducing and oxidizing agents and transition metal complexes. Alkyllithium reagents can be used for the metallation of monoalkyl-substituted triazenes. However, triazenes are unstable against brønsted acids and some lewis acids. Together with triazene they form diazonium salts and amines.

The T1-linker consists of 3,3-dialkyl-1-aryltriazenes, that are linked to the solid support through the alkyl chain, either with a dibenzyl- or with a piperazinyl-type. This enables the syntheses of functionalized aryls. The synthesis starts with the diazotization of an aniline with a nitrite reagent. The immobilization on solid support is carried out using benzylaminopolystyrene or piperazinylmethylpolystyrene resins. The obtained triazenes can be functionalized in different ways. For cleavage the triazene is treated with acid and the reusable amino resin and the aryldiazonium salt, which can be transformed in situ, are obtained in high yield and purity.

 

In contrast to the T1-linker the T2-linker is based on immobilized aryldiazonium ions. The coupling of these diazonium salts can be performed with aliphatic as well as aromatic primary or secondary amines. The T2-triazenes can be functionalized in the same way as the T1-triazenes. Primary amines can be modified at the free N-H position after immobilization to gain a broader range of products.

Our group performs solid phase synthesis not only for the development of new linkers, but also for the synthesis of transporter molecules and natural products.

 

Solid phase Ynamide chemistry (Marie Curie ECHONET project)

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Inamid-Synthese
Inamid-Synthese

Ynamide chemistry has been investigated for over forty years and has been shown to provide a convenient access to a wide range of heterocycles including pyridines, isoxazoles and others. However, to date the ynamide chemistry has not been advanced to a solid phase platform. The development of a solid-supported sulphonynamide system allows for the quick synthesis of libraries of drug-like heterocyclic compounds that are being screened for their biological activity.