Nodulisporic acid side-chain modifications: access to the 2", 3", 4", and 6" registers.
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.
Chakravarty
Prasun K
PK
Merck Research Laboratories, PO Box 2000, RY800-B101, Rahway, NJ 07065-0900, USA.
Shih
Thomas L
TL
Colletti
Steven L
SL
Ayer
Michelle B
MB
Snedden
Christine
C
Kuo
Howard
H
Tyagarajan
Sriram
S
Gregory
Lynn
L
Zakson-Aiken
Michelle
M
Shoop
Wesley L
WL
Schmatz
Dennis M
DM
Wyvratt
MatthewJ
M
Fisher
Michael H
MH
Meinke
Peter T
PT
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
D000475:Alkenes; D007211:Indoles; D007306:Insecticides; C110703:nodulisporic acid A