Total synthesis of A-315675: a potent inhibitor of influenza neuraminidase.
A concise, stereocontrolled, and practical synthesis of a neuraminidase inhibitor consisting of a highly functionalized D-proline scaffold is described. Key features involve a stereocontrolled addition of a propiolate ester to a chiral nonracemic nitrone derived originally from D-serine and the manipulation of acyclic and cyclic motifs en route to the target in 12.8% overall yield over 22 steps. Several crystalline intermediates were suitable for single-crystal X-ray analysis.
Hanessian
Stephen
S
Department of Chemistry, Université de Montréal, C.P. 6128, Succursale Centre-ville, Montréal, Québec H3C 3J7, Canada. stephen.hanessian@umontreal.ca
Bayrakdarian
Malken
M
Luo
Xuehong
X
D000998:Antiviral Agents / Q000138:chemical synthesis*; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000737:chemistry*; D015394:Molecular Structure; D009439:Neuraminidase / Q000037:antagonists & inhibitors*; D009975:Orthomyxoviridae / Q000201:enzymology; D011759:Pyrrolidines / Q000138:chemical synthesis*; D013237:Stereoisomerism
C456059:A 315675; D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D011759:Pyrrolidines; D009439:Neuraminidase