Stereoselective synthesis of an anti-HIV drug candidate

• Published in: Chirality (New York, N.Y.) Vol. 17; no. S1; pp. S149 - S158
• Main Authors: Conlon, David A., Jensen, Mark S., Palucki, Michael, Yasuda, Nobuyoshi, Um, Joann M., Yang, Chunhua, Hartner, Frederick W., Tsay, Fuh-Rong, Hsiao, Yi, Pye, Philip, Rivera, Nelo R., Hughes, David L.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 2005
• Subjects: allylic alkylation; asymmetric catalysis; enantiomeric purity; enantioselectivity; Human immunodeficiency virus
• ISSN: 0899-0042; 1520-636X
• DOI: 10.1002/chir.20137

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%. Chirality 17:S149–S158, 2005. © 2005 Wiley‐Liss, Inc.