title: Nodulisporic acid side-chain modifications: access to the 2", 3", 4", and 6" registers.
abstract: Efficient routes to access the 2", 3", 4", and 6" registers of the nodulisporic acid (NsA) side chain are disclosed. A mild one-carbon, Ph(2)CdoublebondNCH(2)CtriplebondN mediated homologation of NsA's 3"-aldehyde permitted access to the 4"-register. Curtius reaction of NsA's 3"-acid yielded the corresponding 2"-aldehyde 4 from which the unnatural Delta(2",3")-olefin isomer 2b was obtained. In addition, Arndt-Eistert reactions of the parent NsA permitted a one-carbon homologation to the 6" register. These efforts identified new analogues with significant flea activity and illustrated the biological significance of unsaturation at the 1",2" register.
authors.affiliation: Merck Research Laboratories, PO Box 2000, RY800-B101, Rahway, NJ 07065-0900, USA.
authors.forename: Prasun K
authors.initials: PK
authors.lastname: Chakravarty
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Shih
authors.forename: Steven L
authors.initials: SL
authors.lastname: Colletti
authors.forename: Michelle B
authors.initials: MB
authors.lastname: Ayer
authors.forename: Christine
authors.initials: C
authors.lastname: Snedden
authors.forename: Howard
authors.initials: H
authors.lastname: Kuo
authors.forename: Sriram
authors.initials: S
authors.lastname: Tyagarajan
authors.forename: Lynn
authors.initials: L
authors.lastname: Gregory
authors.forename: Michelle
authors.initials: M
authors.lastname: Zakson-Aiken
authors.forename: Wesley L
authors.initials: WL
authors.lastname: Shoop
authors.forename: Dennis M
authors.initials: DM
authors.lastname: Schmatz
authors.forename: MatthewJ
authors.initials: M
authors.lastname: Wyvratt
authors.forename: Michael H
authors.initials: MH
authors.lastname: Fisher
authors.forename: Peter T
authors.initials: PT
authors.lastname: Meinke
mesh_terms: D000475:Alkenes; D000818:Animals; D004305:Dose-Response Relationship, Drug; D007211:Indoles / Q000737:chemistry* / Q000494:pharmacology; D007306:Insecticides / Q000138:chemical synthesis* / Q000494:pharmacology; D005423:Siphonaptera / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D000475:Alkenes; D007211:Indoles; D007306:Insecticides; C110703:nodulisporic acid A