title: Total synthesis of phorboxazole A via de novo oxazole formation: strategy and component assembly.
abstract: The phorboxazole natural products are among the most potent inhibitors of cancer cell division, but they are essentially unavailable from natural sources at present. Laboratory syntheses based upon tri-component fragment coupling strategies have been developed that provide phorboxazole A and analogues in a reliable manner and with unprecedented efficiency. This has been orchestrated to occur via the sequential or simultaneous formation of both of the natural product's oxazole moieties from two serine-derived amides, involving oxidation-cyclodehydrations. The optimized preparation of three pre-assembled components, representing carbons 3-17, 18-30, and 31-46, has been developed. This article details the design and syntheses of these three essential building blocks. The convergent coupling approach is designed to facilitate the incorporation of structural changes within each component to generate unnatural analogues, targeting those with enhanced therapeutic potential and efficacy.
authors.forename: Bo
authors.initials: B
authors.lastname: Wang
authors.forename: T Matthew
authors.initials: TM
authors.lastname: Hansen
authors.forename: Ting
authors.initials: T
authors.lastname: Wang
authors.forename: Dimao
authors.initials: D
authors.lastname: Wu
authors.forename: Lynn
authors.initials: L
authors.lastname: Weyer
authors.forename: Lu
authors.initials: L
authors.lastname: Ying
authors.forename: Mary M
authors.initials: MM
authors.lastname: Engler
authors.forename: Melissa
authors.initials: M
authors.lastname: Sanville
authors.forename: Christopher
authors.initials: C
authors.lastname: Leitheiser
authors.forename: Mathias
authors.initials: M
authors.lastname: Christmann
authors.forename: Yingtao
authors.initials: Y
authors.lastname: Lu
authors.forename: Jiehao
authors.initials: J
authors.lastname: Chen
authors.forename: Nicholas
authors.initials: N
authors.lastname: Zunker
authors.forename: Russell D
authors.initials: RD
authors.lastname: Cink
authors.forename: Feryan
authors.initials: F
authors.lastname: Ahmed
authors.forename: Chi-Sing
authors.initials: CS
authors.lastname: Lee
authors.forename: Craig J
authors.initials: CJ
authors.lastname: Forsyth
mesh_terms: D001688:Biological Products / Q000138:chemical synthesis / Q000737:chemistry; D004987:Ethers / Q000737:chemistry; D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis* / Q000737:chemistry*; D008958:Models, Molecular; D008968:Molecular Conformation; D010080:Oxazoles / Q000138:chemical synthesis* / Q000737:chemistry*; D013237:Stereoisomerism; D013379:Substrate Specificity
chemical_list: D001688:Biological Products; D004987:Ethers; D006576:Heterocyclic Compounds, 4 or More Rings; D010080:Oxazoles; C408887:phorboxazole A