AMEBA-linker

Scheme 7.93 Preparation of an N-imidazolium-based soluble AMEBA linker.

The AMEBA linker " was installed upon NaH-mediated alkylation of Merrifield resin with 4-hydroxy-2-methoxy-benzaldehyde in DMF at 120°C for 5 min under microwave irradiation (Scheme 8.20). The authors then chose to attach 4-methyl-3-nitroaniline to the linker through a previously established two-step reductive amination protocol, involving the imine formation mediated by Ti(0 Pr)4 followed by reduction of the imine using NaBH (OAc)3 (Scheme 8.20). The free amino group was then acylated with 4-(chloromethyl) benzoyl chloride using DIPEA in DMF to form the corresponding amide. 

In a recent study, the group of Buijsman presented a microwave-mediated preparation of a different N-imidazolium-based ionic analogue of the well-known AMEBA solid support (Scheme 7.93). With this soluble support, a set of various sulfonamides and amides was prepared, and furthermore the use of this novel linker in the synthesis of a potent analogue of the antiplatelet drug tirofiban was presented [106]. 

AA, amino acid AC, acid-cleavable linker [4-(hydroxymethyl)-3-methoxy-phenoxy]acetic acid ADCC, 4-acetyl-3,5-dioxo-l-methylcyclohexane carboxylic acid AMEBA, acid-sensitive methoxybenzyl resin ANP, 3-amino(2-nitrophenyl)propionyl BAL, backbone amide linker 9-BBN,... 

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