MBX-36, SHU-9119

Chemical Name: N-Acetyl-L-norleucyl-L-aspartyl-L-histidyl-3-(2-naphthyl)-D-alanyl-L-arginyl-L-tryptophyl-L-lysinamide cyclic C-4.2-N-6.7-amide
CAS No. 168482-23-3
项目整合开发状态: Preclinical
项目研究机构: Oregon Health and Science University (Originator), University of Arizona (Originator)
合成路线:The peptide was synthesized by a solid-phase method using a p-methylbenzhydrylamine resin to which N1-Boc-N6-Fmoc-L-lysine (I) was coupled giving (II).To this solid phase the following protected amino acids Nalpha-Boc-N1-formyl-L-tryptophan (III),Nalpha-Boc-Nomega-Tos-L-arginine (V),Nalpha-Boc-D-(2-naphthyl)alanine (VII),Nalpha-Boc-Npi-L-histidine (IX) and Nalpha-Boc-Ogamma-Fm-L-aspartic acid (XI) were sequentially coupled yielding resins (IV),(VI),(VIII),(X) and (XII).

合成路线:The coupling sequences were continued with Nalpha-Boc-L-norleucine (XIII) to afford resin (XIV).Elimination of the Fmoc and OFm protecting groups of (XIV) was performed with piperidine in NMP allowing the formation of the lactam ring by cyclization with BOP and DIEA in NMP providing the macrocyclic lactam (XV).

合成路线:Elimination of the Boc protecting group of (XV) with trifluoroacetic acid followed by acetylation of the free amino group with acetic anhydride yielded resin (XVI) with a terminal acetyl group.Finally,this resin was treated with FH,anisole and dithioethane to complete the deprotection process and elimnate the solid phase resin affornig the target macrocyclic peptide.