- Asymmetric One-Pot Synthesis of (3R,3aS,6aR)-Hexahydrofuro[2,3-b]furan-3-ol: A Key Component of Current HIV Protease Inhibitors
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A concise and efficient synthesis of (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-ol, a key building block for several clinical and experimental HIV protease inhibitors including the highly important drug darunavir, was achieved via a one-pot procedure using furan and Cbz-protected glycol aldehyde as starting materials. A [2+2]-photocycloaddition between both reactants which can be prepared from wood-based starting materials according to the principles of xylochemistry, followed by hydrogenation and lipase-catalyzed kinetic resolution afforded the target compound in high yield and up to 99% ee.
- Sevenich, Adrian,Liu, Gong-Qing,Arduengo, Anthony J.,Gupton, B. Frank,Opatz, Till
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p. 1218 - 1223
(2018/06/18)
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- Research and development of an efficient synthesis of hexahydrofuro[2,3-b] furan-3-ol moiety - a key component of the HIV protease inhibitor candidates
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A highly efficient method for synthesizing racemic hexahydrofuro[2,3-b] furan-3-ol has been developed utilizing a lanthanide catalyst, such as Yh(fod)3, to promote condensation of 23-dihydrofuran and glycolaldehyde dimer. Access to either optically enriched enantiomer of bisfuran alcohol can be obtained by using this method employing chiral ligands with the lanthanide catalyst In support of Gilead Sciences' protease inhibitor project, this method has been demonstrated to be a robust and scalable process with potential application for the construction of a variety of furo[2,3-b]furan derivatives.
- Yu, Richard H.,Polniaszek, Richard P.,Becker, Mark W.,Cook, Charles M.,Yu, Lok Him L.
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p. 972 - 980
(2012/12/30)
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- PROCESS FOR PREPARATION OF HIV PROTEASE INHIBITORS
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A process for the synthesis of bisfuran intermediates useful for preparing antiviral HIV protease inhibitor compounds is hereby disclosed.
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Page/Page column 28
(2008/06/13)
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- Evaluation of furofuran as a P2 ligand for symmetry-based HIV protease inhibitors
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The hexahydrofurofuranyloxy group was evaluated as a conformationally constrained P2 ligand for symmetry-based HIV protease inhibitors. A number of compounds showed nM level activity against HIV in MT4 cells and lower protein binding than the licensed protease inhibitor ritonavir. However, replacement of 5-thiazole of ritonavir with a furofuran caused a reduction of the bioavailability in vivo.
- Chen, Xiaoqi,Li, Lin,Kempf, Dale J.,Sham, Hing,Wideburg, Norman E.,Saldivar, Ayda,Vasavanonda, Sudthida,Marsh, Kennan C.,McDonald, Edith,Norbeck, Daniel W.
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p. 2847 - 2852
(2007/10/03)
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- SINTHESIS AND OPTICAL RESOLUTION OF HIGH AFFINITY P2-LIGANDS FOR HIV-1 PROTEASE INHIBITORS
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Racemic bis-tetrahydrofuran ligand 6 was efficiently synthesized utilizing catalytic cobaloxime 10 mediated radical cyclization as the key step.Optical resolution of the racemic alcohol with immobilized-Amano lipase, afforded optically pure ligands.
- Ghosh, Arun K.,Chen, Yan
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p. 505 - 508
(2007/10/02)
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