Efficient synthesis of (3R,3aS,6aR)- hexahydrofuro[2,3-b]furan-3-ol from glycolaldehyde.
A one-step diastereoselective (up to 98:2) synthesis of the bis-furan alcohol of Darunavir and other HIV drug candidates has been achieved utilizing the novel cyclization of glycolaldehyde and 2,3-dihydrofuran. The cycloaddition was catalyzed by a variety of catalysts including those formed from tin(II) triflate and common chiral ligands such as BINAP and Evans's box ligands. An efficient and unique enzymatic process enhanced the enantiomeric purity to provide the target in optically pure form.
Canoy
Will L
WL
Chemical Development, GlaxoSmithKline, Research Triangle Park, NC 27709, USA.
Cooley
Bob E
BE
Corona
John A
JA
Lovelace
Thomas C
TC
Millar
Alan
A
Weber
Aimee M
AM
Xie
Shiping
S
Zhang
Yong
Y
D000447:Aldehydes / Q000737:chemistry*; D019380:Anti-HIV Agents / Q000138:chemical synthesis*; D002384:Catalysis; D003500:Cyclization; D005663:Furans / Q000737:chemistry*; D008024:Ligands; D013237:Stereoisomerism
D000447:Aldehydes; D019380:Anti-HIV Agents; D005663:Furans; D008024:Ligands; C513052:hexahydrofuro(2,3-b)furan-3-ol