title: Synthesis and biological evaluation of analogues of the marine cyclic depsipeptide obyanamide.
abstract: On the basis of the total synthesis of obyanamide, 20 analogues of this marine cyclic depsipeptide have been synthesized by (i) preparation of the tripeptide fragments in the western hemisphere using Z/OtBu protocol; (ii) preparation of the dipeptide fragments in the eastern hemisphere using Boc/OMe protocol; and (iii) fragments coupling, removal of protecting groups (Boc and OtBu, in one pot), and macrocyclizaion in the last step. The cytotoxic test showed that three synthetic compounds exhibited moderate activities against HL-60, KB, LOVO, and A549 cell lines. According to the results, the β-amino acid residue was found to play a critical role in the biological activities. Additionally, the ester bond along with the Ala(Thz) moiety was also essential for biological activities. However, it seems too early to draw a conclusion that the N-methylation of Val/Phe can lead to higher or lower cytotoxic activities.
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Fudan University, Shanghai 201203, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Ning
authors.initials: N
authors.lastname: Ding
authors.forename: Yingxia
authors.initials: Y
authors.lastname: Li
mesh_terms: D001688:Biological Products / Q000138:chemical synthesis / Q000737:chemistry; D047630:Depsipeptides / Q000138:chemical synthesis* / Q000737:chemistry*; D004151:Dipeptides / Q000737:chemistry; D005563:Formic Acid Esters / Q000737:chemistry; D015394:Molecular Structure; D012623:Seawater
chemical_list: D001688:Biological Products; D047630:Depsipeptides; D004151:Dipeptides; D005563:Formic Acid Esters; C449753:obyanamide; C000345:t-butyloxycarbonyl group