title: Collective total synthesis of englerin A and B, orientalol E and F, and oxyphyllol: application of the organocatalytic [4+3] cycloaddition reaction.
abstract: The concise collective total synthesis of englerin A and B, orientalol E and F, and oxyphyllol has been accomplished in 10-15 steps, with the total synthesis of orientalol E and oxyphyllol being achieved for the first time. The success obtained was enabled by the realization of the [4+3] cycloaddition reaction of 9 and 10. Other features of the synthesis include 1) the intramolecular Heck reaction to access the azulene core, 2) the epoxidation-S(N)2' reduction sequence to access the allylic alcohol, 3) the efficient regioselective and stereoselective formal hydration of the bridging C=C bond in the synthesis of englerins, and 4) the late-stage chemo- and stereoselective C-H oxidation in the synthesis of orientalol E. The total synthesis of these natural products has enabled the structural revision of oxyphyllol and established the absolute stereochemical features of the organocatalytic [4+3] cycloaddition reaction. The identification of 5 as the natural product oxyphyllol, the success in converting 5 to orientalol E, along with the fact that englerins and oxyphyllol were isolated from plants of the same genus Phyllanthus gives support to our proposed biosynthetic pathways. This work may enable detailed biological evaluations of these natural products and their analogues and derivatives, especially of their potential in the fight against renal cell carcinoma (RCC).
authors.affiliation: CAS Key Laboratory of Synthetic Chemistry of Natural Substances Shanghai, Institute of Organic Chemistry, 345 Lingling Road, 200032, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
authors.forename: Shu-Guang
authors.initials: SG
authors.lastname: Chen
authors.forename: Bing-Feng
authors.initials: BF
authors.lastname: Sun
authors.forename: Guo-Qiang
authors.initials: GQ
authors.lastname: Lin
authors.forename: Yong-Jia
authors.initials: YJ
authors.lastname: Shang
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis* / Q000737:chemistry; D001688:Biological Products / Q000138:chemical synthesis* / Q000737:chemistry; D002292:Carcinoma, Renal Cell / Q000737:chemistry* / Q000188:drug therapy*; D002384:Catalysis; D003500:Cyclization; D061565:Cycloaddition Reaction; D010084:Oxidation-Reduction; D045789:Sesquiterpenes, Guaiane / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D001688:Biological Products; D045789:Sesquiterpenes, Guaiane; C534971:englerin A; C551614:englerin B; C583006:orientalol E; C583005:orientalol F