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 non-conventional yeast Pichia anomala). The original synthesis, starting from (–)-Corey lactone benzoate (3aR,4R,5R,6aS)-3, was modified by replacing three synthetic steps (C=C reduction, stereoselective C=O reduction and hydrolysis/deprotection of the benzoate ester) with a one-pot, three-enzymes conversion. Starting from substrate (3aR,4R,5R,6aS)-4 the use of Pichia anomala allows for the obtainment of Lactondiol B (3aR,4R,5R,6aS,3’S)-6 or Lactondiol L (3aR,4R,5R,6aS,3’R)-7, depending on the co-substrate employed: Lactondiol B (3aR,4R,5R,6aS,3’S)-6 was obtained with 68-70% yield using glucose, whereas the use of fumaric acid gave 87% yield of Lactondiol L (3aR,4R,5R,6aS,3’R)-8 in a simple one-pot, three-step biotransformation. In both cases the reactions were also highly stereoselective, with enantiomeric eccesses of products >97%. Different strategies of reaction optimization and improvement, including cells/enzyme immobilization and continuous flow reactor process implementation, will be also discussed.

A new chemoenzymatic approach to the synthesis of latanoprost and bimatoprost / D. Romano, M.L. Contente, F. Molinari, L. Tamborini, A. Pinto, P. Conti. ((Intervento presentato al convegno MECP14 - Multistepp Enzyme Catalyzed Processes tenutosi a Madrid nel 2014.

A new chemoenzymatic approach to the synthesis of latanoprost and bimatoprost

D. Romano
Primo
;
M.L. Contente
Secondo
;
F. Molinari;L. Tamborini;A. Pinto;P. Conti
2014-04-09

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 non-conventional yeast Pichia anomala). The original synthesis, starting from (–)-Corey lactone benzoate (3aR,4R,5R,6aS)-3, was modified by replacing three synthetic steps (C=C reduction, stereoselective C=O reduction and hydrolysis/deprotection of the benzoate ester) with a one-pot, three-enzymes conversion. Starting from substrate (3aR,4R,5R,6aS)-4 the use of Pichia anomala allows for the obtainment of Lactondiol B (3aR,4R,5R,6aS,3’S)-6 or Lactondiol L (3aR,4R,5R,6aS,3’R)-7, depending on the co-substrate employed: Lactondiol B (3aR,4R,5R,6aS,3’S)-6 was obtained with 68-70% yield using glucose, whereas the use of fumaric acid gave 87% yield of Lactondiol L (3aR,4R,5R,6aS,3’R)-8 in a simple one-pot, three-step biotransformation. In both cases the reactions were also highly stereoselective, with enantiomeric eccesses of products >97%. Different strategies of reaction optimization and improvement, including cells/enzyme immobilization and continuous flow reactor process implementation, will be also discussed.
Settore CHIM/11 - Chimica e Biotecnologia delle Fermentazioni
Settore CHIM/08 - Chimica Farmaceutica
A new chemoenzymatic approach to the synthesis of latanoprost and bimatoprost / D. Romano, M.L. Contente, F. Molinari, L. Tamborini, A. Pinto, P. Conti. ((Intervento presentato al convegno MECP14 - Multistepp Enzyme Catalyzed Processes tenutosi a Madrid nel 2014.
Conference Object
File in questo prodotto:
Non ci sono file associati a questo prodotto.
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/234555
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus ND
  • ???jsp.display-item.citation.isi??? ND
social impact