Stereoselective synthesis of an anti-HIV drug candidate.
The asymmetric synthesis of a Merck anti-HIV drug candidate is described. The target molecule contains four stereogenic centers, three of which are located in a highly functionalized cyclopentane unit. The convergent synthesis involves the preparation of two key advanced intermediates: the cyclopentane unit and a substituted pyrazole unit. The cyclopentane unit was prepared via two different procedures; a highly diastereoselective Diels-Alder reaction with a chiral oxazolidinone auxiliary and a sequence that incorporated a molybdenum-catalyzed asymmetric allylic alkylation reaction to set the stereocenters. The other key step was a highly diastereoselective hydroxyl-directed reductive amination. The overall yield for the 16-step synthesis was 10%.
Conlon
David A
DA
Department of Process Research, Merck Research Laboratories, Rahway, New Jersey 07065-0900, USA. dave_conlon@merck.com
Jensen
Mark S
MS
Palucki
Michael
M
Yasuda
Nobuyoshi
N
Um
Joann M
JM
Yang
Chunhua
C
Hartner
Frederick W
FW
Tsay
Fuh-Rong
FR
Hsiao
Yi
Y
Pye
Philip
P
Rivera
Nelo R
NR
Hughes
David L
DL