title: Diversity-oriented synthesis of Lycopodium alkaloids inspired by the hidden functional group pairing pattern.
abstract: Natural products continue to provide a rich source of inspiration for both chemists and biologists. The efficient synthesis of bioactive natural products or natural product-like molecules has offered tremendous opportunities for complex biological processes exploration and drug discovery. However, because natural products usually contain numerous stereogenic centres and polycyclic ring systems, significant synthetic challenges remain. Here we employ the build/couple/pair strategy that is frequently used in diversity-oriented synthesis to obtain skeletally diverse compounds with complexities comparable to natural products. Inspired by the functional group pairing patterns hidden in Lycopodium alkaloids, we efficiently and in parallel construct four natural products, (+)-Serratezomine A, (-)-Serratinine, (+)-8α-Hydroxyfawcettimine and (-)-Lycoposerramine-U, as well as six different unnatural scaffolds, following the advanced build/couple/pair algorithm. This newly developed strategy is expected to be applied to the efficient synthesis of other complex natural products possessing functional group pairing patterns as well as skeletally diverse natural product-like molecules.
authors.affiliation: 1] School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, China [2] National Institute of Biological Sciences (NIBS), Beijing 102206, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: 1] School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, China [2] National Institute of Biological Sciences (NIBS), Beijing 102206, China.
authors.forename: Jinbao
authors.initials: J
authors.lastname: Wu
authors.affiliation: 1] School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, China [2] National Institute of Biological Sciences (NIBS), Beijing 102206, China.
authors.forename: Benke
authors.initials: B
authors.lastname: Hong
authors.affiliation: 1] School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, China [2] National Institute of Biological Sciences (NIBS), Beijing 102206, China.
authors.forename: Wenying
authors.initials: W
authors.lastname: Ai
authors.affiliation: 1] School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, China [2] National Institute of Biological Sciences (NIBS), Beijing 102206, China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Wang
authors.affiliation: National Institute of Biological Sciences (NIBS), Beijing 102206, China.
authors.forename: Houhua
authors.initials: H
authors.lastname: Li
authors.affiliation: 1] National Institute of Biological Sciences (NIBS), Beijing 102206, China [2] Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Department of Chemical Biology, College of Chemistry and Molecular Engineering, Synthetic and Functional Biomolecules Center, and Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China.
authors.forename: Xiaoguang
authors.initials: X
authors.lastname: Lei
mesh_terms: D000470:Alkaloids / Q000737:chemistry* / Q000302:isolation & purification; D001688:Biological Products / Q000737:chemistry* / Q000302:isolation & purification; D040761:Biomimetic Materials / Q000138:chemical synthesis*; D002623:Chemistry Techniques, Analytical; D003500:Cyclization; D006575:Heterocyclic Compounds, 3-Ring / Q000138:chemical synthesis* / Q000737:chemistry / Q000302:isolation & purification; D007212:Indolizines / Q000737:chemistry / Q000302:isolation & purification; D032502:Lycopodium / Q000737:chemistry*; D015394:Molecular Structure
chemical_list: D000470:Alkaloids; D001688:Biological Products; D006575:Heterocyclic Compounds, 3-Ring; D007212:Indolizines; C415194:serratezomine A; C009245:serratinine