title: Synthesis and Insecticidal Activity of Spinosyns with C9-O-Benzyl Bioisosteres in Place of the 2',3',4'-Tri-O-methyl Rhamnose.
abstract: The spinosyns are fermentation-derived natural products active against a wide range of insect pests. They are structurally complex, consisting of two sugars (forosamine and rhamnose) coupled to a macrocyclic tetracycle. Removal of the rhamnose sugar results in a >100-fold reduction in insecticidal activity. C9-O-benzyl analogues of spinosyn D were synthesized to determine if the 2',3',4'-tri-O-methyl rhamnose moiety could be replaced with a simpler, synthetic bioisostere. Insecticidal activity was evaluated against larvae of Spodoptera exigua (beet armyworm) and Helicoverpa zea (corn earworm). Whereas most analogues were far less active than spinosyn D, a few of the C9-O-benzyl analogues, such as 4-CN, 4-Cl, 2-isopropyl, and 3,5-diOMe, were within 3-15 times the activity of spinosyn D for larvae of S. exigua and H. zea. Thus, although not yet quite as effective, synthetic bioisosteres can substitute for the naturally occurring 2',3',4'-tri-O-methyl rhamnose moiety.
authors.affiliation: Dow AgroSciences, Discovery Research, 9330 Zionsville Road, Indianapolis, Indiana 46268, United States.
authors.forename: M Paige
authors.initials: MP
authors.lastname: Oliver
authors.affiliation: Dow AgroSciences, Discovery Research, 9330 Zionsville Road, Indianapolis, Indiana 46268, United States.
authors.forename: Gary D
authors.initials: GD
authors.lastname: Crouse
authors.affiliation: Dow AgroSciences, Discovery Research, 9330 Zionsville Road, Indianapolis, Indiana 46268, United States.
authors.forename: David A
authors.initials: DA
authors.lastname: Demeter
authors.affiliation: Dow AgroSciences, Discovery Research, 9330 Zionsville Road, Indianapolis, Indiana 46268, United States.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Sparks
mesh_terms: D000818:Animals; D007306:Insecticides / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity*; D007814:Larva / Q000187:drug effects / Q000254:growth & development; D018942:Macrolides / Q000737:chemistry* / Q000633:toxicity*; D015394:Molecular Structure; D009036:Moths / Q000187:drug effects / Q000254:growth & development; D012210:Rhamnose / Q000737:chemistry*
chemical_list: D007306:Insecticides; D018942:Macrolides; C114884:spinosyn D; D012210:Rhamnose
keywords: macrocyclic lactone insecticides; natural products; rhamnose sugar bioisostere; semisynthetic analogues; spinosyns