title: A flexible asymmetric approach to methyl 5-alkyltetramates and its application in the synthesis of cytotoxic marine natural product belamide A.
abstract: By using a methyl tetramate derivative (R)- or (S)-9 as a novel chiral building block, a direct, flexible, and highly enantioselective approach to methyl (R)- or (S)-5-alkyltetramates (2) is disclosed. Among the synthesized methyl 5-alkyltetramates 2, methyl 5-methyltetramate (2 a) is found in cytotoxic mirabimide E (4) and dysideapyrrolidone (5), and methyl 5-benzyltetramate (2 g) is a substructure in the potent antineoplastic dolastatin 15 (3). On the basis of this method, the first asymmetric synthesis of the antimitotic tetrapeptide belamide A (7) has been achieved in seven steps from (S)-9, with an overall yield of 23.8 %. Not only have the structure and absolute configuration of (+)-belamide A (7) been confirmed, but also the solvent used for recording the (13) C NMR spectrum, the (13) C NMR spectrum data correlation, and optical rotation data of natural belamide A (7) have been revised.
authors.affiliation: Department of Chemistry, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian 361005, PR China.
authors.forename: Hong-Qiao
authors.initials: HQ
authors.lastname: Lan
authors.forename: Jian-Liang
authors.initials: JL
authors.lastname: Ye
authors.forename: Ai-E
authors.initials: AE
authors.lastname: Wang
authors.forename: Yuan-Ping
authors.initials: YP
authors.lastname: Ruan
authors.forename: Pei-Qiang
authors.initials: PQ
authors.lastname: Huang
mesh_terms: D001688:Biological Products / Q000138:chemical synthesis* / Q000737:chemistry*; D008387:Marine Toxins / Q000737:chemistry*; D008968:Molecular Conformation; D015394:Molecular Structure; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry*; D011760:Pyrrolidinones / Q000138:chemical synthesis* / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D001688:Biological Products; D008387:Marine Toxins; D009842:Oligopeptides; D011760:Pyrrolidinones; C556090:belamide A