156928-09-5Relevant articles and documents
A stereoselective anti-aldol route to (3R,3aS,6aR)-hexahydrofuro[2,3-b] furan-3-ol: A key ligand for a new generation of HIV protease inhibitors
Ghosh, Arun K.,Li, Jianfeng,Perali, Ramu Sridhar
, p. 3015 - 3018 (2006)
A stereoselective synthesis of (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-ol, an important high affinity P2-ligand, in high enantiomeric excess (>99%) is reported. The synthesis features an ester-derived titanium enolate based highly stereoselective anti-aldol reaction as the key step. Georg Thieme Verlag Stuttgart.
Comparing the greenness and sustainability of three routes to an HIV protease inhibitor intermediate
Akakios, Stephanie Gina,Bode, Moira Leanne,Sheldon, Roger Arthur
, p. 3334 - 3347 (2021)
The greenness and sustainability of three different routes for the synthesis of (3R,3aS,6aR)-hexahydrofuro [2,3-b] furan-3-ol (bis-furan alcohol), an advanced intermediate for a group of HIV protease inhibitors, including the FDA approved darunavir, used in antiretroviral (ARV) therapy, were compared. The method involved a comparison of (i) waste generated using theE-factor and relative to industrial benchmarks using the innovative Green Aspiration Level (iGAL) method, (ii) solvent usage on the basis of solvent intensity (SI) and properties according to the GSK solvent guide, and (iii) Green Motion scores according to the MANE methodology.
Efficient synthesis of 3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-ol from glycolaldehyde
Canoy, Will L.,Cooley, Bob E.,Corona, John A.,Lovelace, Thomas C.,Millar, Alan,Weber, Aimee M.,Xie, Shiping,Zhang, Yong
, p. 1103 - 1106 (2008)
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 cyclizatlon 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.
A Concise One-Pot Organo- and Biocatalyzed Preparation of Enantiopure Hexahydrofuro[2,3-b]furan-3-ol: An Approach to the Synthesis of HIV Protease Inhibitors
Kanemitsu, Takuya,Inoue, Mizuho,Yoshimura, Nono,Yoneyama, Kazutoshi,Watarai, Rie,Miyazaki, Michiko,Odanaka, Yuki,Nagata, Kazuhiro,Itoh, Takashi
, p. 1874 - 1880 (2016)
A simple and efficient one-pot synthesis of enantiopure hexahydrofuro[2,3-b]furan-3-ol, a crucial component of HIV-1 protease inhibitors, was developed. The one-pot process involves an organocatalytic condensation followed by an enzymatic optical resolution. The condensation of 1,2-dihydrofuran and glycolaldehyde was achieved using Schreiner's thiourea catalyst (1 mol-%). A subsequent lipase-catalyzed kinetic resolution gave the target alcohol with >99 % ee. To demonstrate the practicality of this method, Darunavir, an HIV-1 protease inhibitor used to treat multi-drug-resistant HIV, was synthesized.
An Efficient Synthesis of the Bicyclic Darunavir Side Chain Using Chemoenzymatic Catalysis
Charnock, Simon J.,Finnigan, James D.,Hyster, Todd K.,Lim, Jesmine,Riehl, Paul S.
, (2022/03/03)
Herein, we describe a chemoenzymatic synthesis of the bicyclic fragment of Darunavir. A ketoreductase was identified using metagenomic mining to catalyze a highly enantio- and diastereoselective dynamic kinetic resolution of a β-ketolactone. Subsequent lactone reduction with diisobutylaluminum hydride and phase transfer cyclization affords the bicyclic acetal fragment in 39% yield over four steps.
Ru-catalyzed asymmetric transfer hydrogenation of α-acyl butyrolactone via dynamic kinetic resolution: Asymmetric synthesis of bis-THF alcohol intermediate of darunavir
More, Ganesh V.,Malekar, Pushpa V.,Kalshetti, Rupali G.,Shinde, Mahesh H.,Ramana, Chepuri V.
supporting information, (2021/02/16)
The Ru-catalyzed enantio- and diastereoselective dynamic kinetic resolution of α-(benzyloxy/benzoyloxy)acyl-γ-butyrolactones has been examined via transfer hydrogenation. Employing the in situ prepared (R,R)-Ru-FsDPEN catalyst, the transfer hydrogenation of using formic acid/triethylamine at rt gave the corresponding (S)-3-((S)-2-(benzyloxy/benzoyloxy)-1-hydroxyethyl)dihydrofuran-2(3H)-one with good to excellent diastereo- and enantioselectivity. One of the resulting hydrogenation product prepared on gram scales was utilized for the synthesis of (3R,3aS,6aR)-hexahydrofuro[2,3–b]furan-3-ol (1), a key synthetic intermediate of various HIV protease inhibitors such as darunavir with excellent enantio- (95% ee) and diastereoselectivities (dr 95:5).
