Study On Syntheses Of Natural Peptides Hirsutellide A And Tasiamide

Retrosynthetic analysis and total synthesis of natural cyclopeptide Hirsutellide Awere described in this paper.2R-hydroxy-3-phenylpropanoic acid benzyl ester as fragment one wassynthesized from D-Phe through diazotization hydrolysis and esterification by benzylalcohol in a yield of 56%;(tert-Butoxycarbonyl-methyl-amino)-acetic acid asfragment two was obtained in a yield of 83% from glycine through Bocamino-protection and N-methylation;2-tert-Butoxycarbonylamino-3-methyl-pentanoic acid as fragment three was the product of Boc protection from L-Ile. Theyield is 99%.Esterification of fragment one with fragment two using DCC provided theprotected didepsipeptide. Removal of its Boc protecting group and coupling withfragment three using HATU-promoted reagent yielded the corresponding protectedtridepsipeptide. The two deprotected precursors, which the benzyl ester and the Bocgroup were removed respectively, coupled with BOP-Cl reagent to afford the linearhexadepsipetide in an overall yield of 45% based on fragment two.Finally, the microcyclization mediated by FDPP gave natural depsipeptideHirsutellide A in 22% yield from the linear precursor after deprotecting benzyl esterand the Boc group, respectively.In addition, the synthesis of Tasiamide was investigated preliminarily.N-Boc-Me-D-Phe-OH was obtained from D-Phe through Boc protection andN-methylation. Then it was coupled with L-Pro-OMe using DCC reagent to yielddipeptide. Removal of the Boc protected group and coupling with Fmoc-Gly-Cl gavethe tripeptide in an overall yield of 20% (based on D-Phe).The dipeptide was obtained from L-Ile through diazotization hydrolysis andcoupling with L-Leu-OMe using DCC reagent in an overall yield of 56% (based onL-Ile).The structures of the key intermediates and the target compounds obtained inthis paper were determined by nuclear magnetic resonance spectra (NMR), IR, etc.