Synthetic approaches to a chiral 4-amino-3-hydroxy piperidine with pharmaceutical relevance.
Four synthetic strategies were evaluated towards the preparation of (-)-(3R,4R)-1-benzyl-4-(benzylamino)piperidin-3-ol (1), which was constructed with control over the relative and absolute stereochemistry of the 4,3-amino alcohol moiety. The first strategy employed a novel Rh(I) catalyzed asymmetric hydrogenation, while two other strategies exploited the existing stereochemistry in 2-deoxy-D-ribose, and the fourth explored both biocatalytic and classical resolution techniques as a means to impart enantioenrichment to racemic intermediates en route to targeted structure (-)-1.
Chemical Development, Bristol-Myers Squibb Company, One Squibb Drive, New Brunswick, New Jersey 08903, USA. Adrian.Ortiz@bms.com
Adrian
A
Ortiz
Ian S
IS
Young
James R
JR
Sawyer
Yi
Y
Hsiao
Amarjit
A
Singh
Masano
M
Sugiyama
R Michael
RM
Corbett
Melissa
M
Chau
Zhongping
Z
Shi
David A
DA
Conlon
D006865:Hydrogenation; D008958:Models, Molecular; D015394:Molecular Structure; D010880:Piperidines / Q000138:chemical synthesis*; D013237:Stereoisomerism
D010880:Piperidines