Trimellitic anhydride linker (TAL) - highly orthogonal conversions of primary amines employed in the parallel synthesis of labeled carbohydrate derivatives

Trimellitic Anhydride Linker (TAL) was introduced as an anchor in solid-phase synthesis allowing for immobilization of primary amines as phThALimide derivatives. 1,2-Anhydro trimellitic acid chloride (trimellitic acid = 1,2,4-benzene tricarboxylic acid) was coupled to methyl aminomethyl polystyrene at 0degreesC. Polymer-bound phthalimides were formed from primary amines by heating, preferably assisted by microwave irradiation, or via a condensation protocol at rt. In the latter case, the intermediary secondary amide was formed in the presence of 4-N,N-dimethylamino pyridine (DMAP), ring closure to the cyclic imide was effected smoothly in the presence of 1-(mesitylene-2-sulfonyl)-3-nitro-1H- 1,2,4-triazole (MSNT) as condensation agent. The linker was stable under a broad range of reaction conditions including strong acid, base, and oxidants, respectively. Efficient cleavage could be effected by treatment with 1% hydrazine or with ethylenediamine, respectively. Alternatively, products were released by a safety-catch procedure. Phthalimides were reduced with borohydrides, preferably with LiBH4, and products were afforded in high purity and with excellent yields by treatment with dilute acid (5% trifluoroacetic acid (TFA)). Employment of the linker for the synthesis of labeled carbohydrates was demonstrated involving efficient solid-supported glycosylation. (C) 2003 Elsevier Science Ltd. All rights reserved.