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Usage

Uses

Used in Pharmaceutical Industry:
N-[(1S,2R)-2-Hydroxy-3-[(2-Methylpropyl)[(4-nitrophenyl)sulfonyl]amino]-1-(phenylmethyl)propyl]carbamic Acid (3R,3aS,6aR)-Hexahydrofuro[2,3-b]furan-3-yl Ester is used as an intermediate in the synthesis of 1-epi-Darunavir (D193505), a second-generation HIV-1 protease inhibitor. N-[(1S,2R)-2-Hydroxy-3-[(2-Methylpropyl)[(4-nitrophenyl)sulfonyl]aMino]-1-(phenylMethyl)propyl]carbaMic Acid (3R,3aS,6aR)-Hexahydrofuro[2,3-b]furan-3-yl Ester plays a crucial role in the development of antiretroviral drugs, which are essential for the treatment of HIV/AIDS.
As an intermediate in the synthesis of 1-epi-Darunavir, N-[(1S,2R)-2-Hydroxy-3-[(2-Methylpropyl)[(4-nitrophenyl)sulfonyl]aMino]-1-(phenylMethyl)propyl]carbaMic Acid (3R,3aS,6aR)-Hexahydrofuro[2,3-b]furan-3-yl Ester contributes to the production of a more potent and selective HIV-1 protease inhibitor. The improved properties of 1-epi-Darunavir, compared to earlier generations of inhibitors, make it a valuable asset in the fight against HIV and AIDS, offering better treatment options for patients and potentially leading to improved outcomes in managing the disease.

Upstream product

• 251105-80-3 N-(3S-amino-2R-hydroxy-4-phenylbutyl)-N-isobutyl-4-nitro-benzenesulfonamide hydrochloride 
• 32315-10-9 bis(trichloromethyl) carbonate 
• 156928-09-5 (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-ol 
• 6066-82-6 1-hydroxy-pyrrolidine-2,5-dione 
• 524-38-9 N-hydroxyphthalimide 
• 664344-42-7 [(1S,2R)-2-hydroxy-3-[(2-methylpropyl)amino]-1-(phenylmethyl)propyl]carbamic acid (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yl ester 
• 98-74-8 4-Nitrobenzenesulfonyl chloride 
• 98760-08-8 (1-oxiranyl-2-phenylethyl)carbamic acid tert-butyl ester 
• 253265-97-3 1-[[[(3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yloxy]carbonyl]oxy]pyrrolidine-2,5-dione 
• 191226-98-9 [(1S,2R)-3-[(4-nitrophenylsulfonyl)(2-methylpropyl)amino]-2-hydroxy-1-(phenylmethyl)propyl]carbamic acid tert-butyl ester 
• 160232-08-6 (2R,3S)-3-tert-butoxycarbonylamino-1-isobutylamino-4-phenyl-2-butanol 

Relevant academic research and scientific papers

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

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.

swiss that Wei method for the preparation of intermediates (by machine translation)

The invention relates to the technical field of heterocyclic chemistry, especially relates to a condensed ring system containing oxygen atoms as the only heterocycle atoms, concretely discloses a preparation method of a Darunavir intermediate. The method comprises the following steps: obtaining a compound of formula (3) by using (3R,3aS,6aR)-hexahydro-furo[2,3-b]furan-3-ol as a raw material to react with triphosgene under alkaline conditions, then directly reacting with a compound of formula (7) to obtain a compound of formula (8); or obtaining a compound of formula (3) to react with an N-hydroxyl compound to prepare active ester, and then reacting with the compound of formula (7) to obtain the compound of formula (8).

PROCESS FOR THE PREPARATION OF (3R,3AS,6AR)-HEXAHYDROFURO [2,3-B] FURAN-3-YL (1S,2R)-3-[[(4-AMINOPHENYL) SULFONYL] (ISOBUTYL) AMINO]-1-BENZYL-2-HYDROXYPROPYLCARBAMATE

The present invention relates to a process for the preparation of (3R,3a S,6aR)-hexa-hydrofuro [2,3-b] furan-3-yl (1S,2R)-3-[[(4-aminophenyl) sulfonyl] (isobutyl) amino]-1-benzyl-2-hydroxypropylcarbamate as well as novel intermediates for use in said process. (3R,3a S,6aR)-hexahydrofuro [2,3-b] furan-3-yl (1S,2R)-3-[[(4-aminophenyl) sulfonyl] (isobutyl) amino]-1-benzyl-2-hydroxypropylcarbamate is particularly useful as an HIV protease inhibitor.

Discovery and selection of TMC114, a next generation HIV-1 protease inhibitor

The screening of known HIV-1 protease inhibitors against a panel of multi-drug-resistant viruses revealed the potent activity of TMC126 on drug-resistant mutants. In comparison to amprenavir, the improved affinity of TMC126 is largely the result of one extra hydrogen bond to the backbone of the protein in the P2 pocket. Modification of the substitution pattern on the phenylsulfonamide P2′ substituent of TMC126 created an interesting SAR, with the close analogue TMC114 being found to have a similar antiviral activity against the mutant and the wild-type viruses. X-ray and thermodynamic studies on both wild-type and mutant enzymes showed an extremely high enthalpy driven affinity of TMC114 for HIV-1 protease. In vitro selection of mutants resistant to TMC114 starting from wild-type virus proved to be extremely difficult; this was not the case for other close analogues. Therefore, the extra H-bond to the backbone in the P2 pocket cannot be the only explanation for the interesting antiviral profile of TMC114. Absorption studies in animals indicated that TMC114 has pharmacokinetic properties comparable to currently approved HIV-1 protease inhibitors.