Trimellitic anhydride linker (TAL)—highly orthogonal conversions of primary amines employed in the parallel synthesis of labeled carbohydrate derivatives
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- 作者：Bauer ; Jö ; rg ; Rademann ; Jö ; rg
- 关键词：solid-phase synthesis ; combinatorial chemistry ; carbohydrates ; amines
- 刊名：Tetrahedron Letters
- 出版年：2003
- 出版时间：June 30, 2003
- 年：2003
- 卷：44
- 期：27
- 页码：5019-5023
- 全文大小：281 K
文摘
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 0°C. 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.