Bimatoprost (1) and Latanoprost (2) are prostaglandin analogues widely used for glaucoma treatment. We have developed a new chemoenzymatic synthesis for 1 and 2, which utilizes a highly stereoselective sequence of biotransformations catalyzed by enzymes belonging to a single microorganism (the yeast Pichia anomala). The original synthesis, starting from (-)-Corey lactone benzoate (3aR,4R,5R,6aS)-3, was modified by replacing three synthetic steps (Cdouble bond, longC reduction, stereoselective Cdouble bond, longO reduction and hydrolysis/deprotection of the benzoate ester) with a one-pot, three-enzymes reaction. The overall biotransformation gave good yields and it was highly stereoselective; noteworthy, by engineering the reaction medium, Cdouble bond, longC reduction could be modulated so that unsaturated (3aR,4R,5R,6aS,3′S)-6 or saturated intermediate (3aR,4R,5R,6aS,3′R)-7 could be preferentially obtained. © 2014 Elsevier B.V. All rights reserved.
A new chemoenzymatic approach to the synthesis of Latanoprost and Bimatoprost / M. Contente, P. Zambelli, S. Galafassi, L. Tamborini, A. Pinto, P. Conti, F. Molinari, D. Romano. - In: JOURNAL OF MOLECULAR CATALYSIS B-ENZYMATIC. - ISSN 1381-1177. - 114(2015 Apr), pp. 7-12. [10.1016/j.molcatb.2014.05.022]
A new chemoenzymatic approach to the synthesis of Latanoprost and Bimatoprost
M. ContentePrimo
;P. ZambelliSecondo
;S. Galafassi
;L. Tamborini;A. Pinto;P. Conti;F. MolinariPenultimo
;D. RomanoUltimo
2015
Abstract
Bimatoprost (1) and Latanoprost (2) are prostaglandin analogues widely used for glaucoma treatment. We have developed a new chemoenzymatic synthesis for 1 and 2, which utilizes a highly stereoselective sequence of biotransformations catalyzed by enzymes belonging to a single microorganism (the yeast Pichia anomala). The original synthesis, starting from (-)-Corey lactone benzoate (3aR,4R,5R,6aS)-3, was modified by replacing three synthetic steps (Cdouble bond, longC reduction, stereoselective Cdouble bond, longO reduction and hydrolysis/deprotection of the benzoate ester) with a one-pot, three-enzymes reaction. The overall biotransformation gave good yields and it was highly stereoselective; noteworthy, by engineering the reaction medium, Cdouble bond, longC reduction could be modulated so that unsaturated (3aR,4R,5R,6aS,3′S)-6 or saturated intermediate (3aR,4R,5R,6aS,3′R)-7 could be preferentially obtained. © 2014 Elsevier B.V. All rights reserved.File | Dimensione | Formato | |
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