Solid-Phase Synthesis of Fmoc-α-Amino Phosphonic Acid Hexamer

Significance

The authors reported a solid-phase synthesis of Fmoc-α-amino phosphonic acid benzyl ester hexamer 7. Thus, resin-supported allylic alcohol linker 3 was prepared by peptide condensation of 9-[(4-methoxyphenyl)diphenylmethoxy]-10-undecenoic acid (1) and TentaGel-NH₂ 2 with DIC and HOBt followed by deprotection. The resulting resin 3 was subjected to the dehydrative condensation with α-amino phosphonic acid 4 ­using DIPEA, HOAt and DIC to give the resin-­supported Fmoc-α-amino phosphonic acid 5. Five-time repetition of Fmoc-removal with piperidine and dehydrative condensation of 4 gave a resin-supported Fmoc-α-amino phosphonic acid hexamer 6. Detachment of an α-amino phosphonic acid hexamer with [RuCp(PPh₃)(MeCN)₂]PF₆ gave the desired product 7.