The synthesis of azadirachtin: a potent insect antifeedant.
We describe in full the first synthesis of the potent insect antifeedant azadirachtin through a highly convergent approach. An O-alkylation reaction is used to unite decalin ketone and propargylic mesylate fragments, after which a Claisen rearrangement constructs the central C8-C14 bond in a stereoselective fashion. The allene which results from this sequence then enables a second critical carbon-carbon bond forming event whereby the [3.2.1] bicyclic system, present in the natural product, is generated via a 5-exo-radical cyclisation process. Finally, using knowledge gained through our early studies into the reactivity of the natural product, a series of carefully designed steps completes the synthesis of this challenging molecule.
Ley
Steven V
SV
Department of Chemistry, University of Cambridge, UK. svl1000@cam.ac.uk
Abad-Somovilla
Antonio
A
Anderson
James C
JC
Ayats
Carles
C
Bänteli
Rolf
R
Beckmann
Edith
E
Boyer
Alistair
A
Brasca
Maria G
MG
Brice
Abigail
A
Broughton
Howard B
HB
Burke
Brenda J
BJ
Cleator
Ed
E
Craig
Donald
D
Denholm
Alastair A
AA
Denton
Ross M
RM
Durand-Reville
Thomas
T
Gobbi
Luca B
LB
Göbel
Michael
M
Gray
Brian Lawrence
BL
Grossmann
Robert B
RB
Gutteridge
Claire E
CE
Hahn
Norbert
N
Harding
Sarah L
SL
Jennens
David C
DC
Jennens
Lynn
L
Lovell
Peter J
PJ
Lovell
Helen J
HJ
de la Puente
Mary L
ML
Kolb
Hartmuth C
HC
Koot
Win-Jan
WJ
Maslen
Sarah L
SL
McCusker
Catherine F
CF
Mattes
Amos
A
Pape
Andrew R
AR
Pinto
Andrea
A
Santafianos
Dinos
D
Scott
James S
JS
Smith
Stephen C
SC
Somers
Andrew Q
AQ
Spilling
Christopher D
CD
Stelzer
Frank
F
Toogood
Peter L
PL
Turner
Richard M
RM
Veitch
Gemma E
GE
Wood
Anthony
A
Zumbrunn
Cornelia
C
D007306:Insecticides / Q000138:chemical synthesis* / Q000737:chemistry; D036701:Limonins / Q000138:chemical synthesis* / Q000737:chemistry; D008968:Molecular Conformation; D013237:Stereoisomerism
D007306:Insecticides; D036701:Limonins; C010329:azadirachtin