- A facile approach to chiral 1,4-benzodioxane toward the syntheses of doxazosin, prosympal, piperoxan, and dibozane
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The process describes the concise synthesis of (R/S)-enantiomers of doxazosin, an antidepressant drug and α-adrenergic receptor antagonists like prosympal, piperoxan, and dibozane in practical yields from easily available (R)-2,3-O-cyclohexylidene-d-glyce
- Rouf, Abdul,Aga, Mushtaq A.,Kumar, Brijesh,Taneja, Subhash Chandra
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p. 6420 - 6422
(2013/11/19)
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- Chemoenzymatic synthesis of piperoxan, prosympal, dibozane, and doxazosin
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The synthesis of both enantiomers of 1,4-benzodioxan-2-carboxylic acid 1, a key synthetic intermediate for the therapeutic agents piperoxan, prosympal, dibozane, and doxazosin was achieved with good yields and high enantioselectivities via the Arthrobacter sp. lipase catalyzed kinetic resolution of ester (±)-17a. The influence of the co-solvents and the immobilization of the lipase upon kinetic resolution demonstrated that immobilized whole cells, in the presence of n-butanol as a co-solvent, resulted in the optimal resolution of the substrate (ee ~99%, E = 535) at 258 mmol (50 g/L) substrate concentration.
- Rouf, Abdul,Gupta, Pankaj,Aga, Mushtaq A.,Kumar, Brijesh,Chaubey, Asha,Parshad, Rajinder,Taneja, Subhash C.
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p. 1615 - 1623
(2013/02/22)
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- Practical chemical and enzymatic technologies for (S)-1,4-benzodioxan-2-carboxypiperizine intermediate in the synthesis of (S)-doxazosin mesylate
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(S)-1,4-Benzodioxan-2-carboxypiperazine (S)-2, the key chiral intermediate for the synthesis of (S)-doxazosin, was prepared utilizing two approaches: (i) enzymatic resolution of ethyl 1,4-benzodioxan-2-carboxylate with an esterase (Serratia) followed by amide formation; (ii) direct resolution of 1,4-benzodioxan-2-carboxypiperazine 2 with D-tartaric acid. An efficient process for the conversion of (S)-2 to (S)-doxazosin mesylate was developed (80% yield, 99.9% e.e.).
- Fang,Grover, Paul,Han, Zhengxu,McConville, Fran X.,Rossi, Richard F.,Olsson, Damase J.,Kessler, Donald W.,Wald, Stephen A.,Senanayake, Chris H.
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p. 2169 - 2174
(2007/10/03)
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