- Catalytic asymmetric synthesis of hexahydro-furofuran-3-ol and its pyran derivatives
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The catalytic asymmetric synthesis of hexahydro-furofuran-3-ol, a key fragment of HIV protease inhibitors, is reported. A signature event is represented by the sequential metal catalysis that combines the Pd-catalyzed asymmetric hydroalkoxylation of ene-alkoxyallene and ring-closing metathesis (RCM). Notably, this unprecedented and highly chemoselective approach allows for a unified access to pyranofuranol and furopyranol derivatives.
- Kim, Mijin,Rhee, Young Ho
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Read Online
- Ru-catalyzed asymmetric transfer hydrogenation of α-acyl butyrolactone via dynamic kinetic resolution: Asymmetric synthesis of bis-THF alcohol intermediate of darunavir
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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).
- More, Ganesh V.,Malekar, Pushpa V.,Kalshetti, Rupali G.,Shinde, Mahesh H.,Ramana, Chepuri V.
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supporting information
(2021/02/16)
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- The efficient synthesis of (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-ol and its isomers
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The stereoselective synthesis of all the possible stereoisomers of bis-tetrahydrofyran alcohol, a ligand used for obtaining HIV protease inhibitors including Darunavir 1 and Brecanavir 2 has been achieved. A key intermediate 4-pentenal 5 was obtained by employing a Wittig olefination-Claisen rearrangement protocol from d-glyceraldehyde derivative 3 as a source of chirality. The 4-pentenal was readily converted in the bis-THF alcohol moiety in three steps.
- Kulkarni, Mukund G.,Shaikh, Yunnus B.,Borhade, Ajit S.,Dhondge, Attrimuni P.,Chavhan, Sanjay W.,Desai, Mayur P.,Birhade, Deekshaputra R.,Dhatrak, Nagorao R.,Gannimani, Ramesh
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experimental part
p. 2394 - 2398
(2010/12/25)
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- METHOD FOR PRODUCING HEXAHYDROFUROFURANOL DERIVATIVE
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Disclosed is a method for producing a compound (IV) which comprises a step for obtaining a compound (III) by reacting a compound (I) with a compound (II) in the presence of an optionally substituted cyclic secondary amine, and a step for obtaining the compound (IV) by removing R1 and R2 from the compound (III) sequentially or at a time and then cyclizing the compound from which the R1 and R2 are removed. Also disclosed is a method for producing a high-purity compound (IV), an intermediate thereof, and a method for producing the intermediate.
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Page/Page column 32-33
(2008/06/13)
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- Production method of hexahydrofurofuranol derivative, intermediate therefor and production method thereof
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The present invention provides a method for producing compound (XIV) useful as an intermediate for pharmaceutical agents efficiently and economically on an industrial scale without using ozone oxidation and highly toxic reagent, and an intermediate used for this method. Particularly, the present invention provides a method for producing a compound having an absolute configuration represented by the formula (XV) and an enantiomer thereof without using a technique such as optical resolution and the like, and an intermediate used for this method. (1) Compound (XIII) as a starting material is led to compound (I), and after introducing a protecting group, subjected to reduction and cyclization to give compound (XIV). Particularly, compound (XIII) as a material is led to compound (I) via compound (XX) to produce compound (XIV). Using an optically active compound (XIII) as a starting material, a compound having an absolute configuration represented by the formula (XV) and the like are produced highly stereoselectively. (2) Compound (XXI) as a starting material is stereoselectively reduced to give compound (XXII), and by introduction of a protecting group, reduction and cyclization, compound (XXVI) is obtained, and by inverting hydroxyl group, compound (XV) is produced. wherein each symbol is as defined in the specification.
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- Production method of hexahydrofurofuranol derivative, intermediate therefor and production method thereof
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The present invention provides a method for producing compound (XIV) useful as an intermediate for pharmaceutical agents efficiently and economically on an industrial scale without using ozone oxidation and highly toxic reagent, and an intermediate used for this method. Particularly, the present invention provides a method for producing a compound having an absolute configuration represented by the formula (XV) and an enantiomer thereof without using a technique such as optical resolution and the like, and an intermediate used for this method. (1) Compound (XIII) as a starting material is led to compound (I), and after introducing a protecting group, subjected to reduction and cyclization to give compound (XIV). Particularly, compound (XIII) as a material is led to compound (I) via compound (XX) to produce compound (XIV). Using an optically active compound (XIII) as a starting material, a compound having an absolute configuration represented by the formula (XV) and the like are produced highly stereoselectively. (2) Compound (XXI) as a starting material is stereoselectively reduced to give compound (XXII), and by introduction of a protecting group, reduction and cyclization, compound (XXVI) is obtained, and by inverting hydroxyl group, compound (XV) is produced. wherein each symbol is as defined in the specification.
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Page/Page column 31
(2008/06/13)
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