title: Biomimetic Assembly Lines Producing Natural Product Analogs: Strategies from a Versatile Manifold to Skeletally Diverse Scaffolds.
abstract: Biosynthetic assembly lines have evolved in nature, adopting divergent processes to produce a vast number of secondary metabolites. Inspired by these biogenetic processes, this account introduces recent investigations by my research group to formulate a synthetic strategy for establishing a biomimetic assembly line. With the aim not only to construct natural product-relevant scaffolds within 5-7 steps, but also to systematically diversify skeletal and stereochemical properties and functional groups, divergent synthetic processes exploiting a versatile manifold have been developed. This approach allows for cost-effective production of skeletally diverse and biologically active natural product analogs inaccessible by other means. Discovery of several lead candidates for a neglected tropical disease is a proof-of-concept of this synthetic approach.
authors.affiliation: Division of Applied Chemistry Graduate School of Engineering, Tokyo University of Agriculture and Technology, 2-24-16 Nakacho, Koganei, Tokyo, 184-8588, Japan.|JST PRESTO, 4-1-8 Honcho, Kawaguchi, Saitama, 332-0012, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Oguri
mesh_terms: D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D001688:Biological Products / Q000138:chemical synthesis* / Q000737:chemistry; D040761:Biomimetic Materials / Q000138:chemical synthesis / Q000737:chemistry; D060326:Chemistry Techniques, Synthetic; D061565:Cycloaddition Reaction; D003512:Cyclohexanones / Q000737:chemistry; D010545:Peroxides / Q000138:chemical synthesis; D010880:Piperidines / Q000737:chemistry; D012717:Sesquiterpenes / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014344:Trypanocidal Agents / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D000470:Alkaloids; D001688:Biological Products; D003512:Cyclohexanones; D010545:Peroxides; D010880:Piperidines; D012717:Sesquiterpenes; D014344:Trypanocidal Agents
keywords: biomimetic synthesis; combinatorial chemistry; cycloaddition reactions; natural products; synthetic drugs