Latanoprost synthesis

Latanoprost, also known as PHXA41 and XA34, is a prostaglandin analogue (more specifically an analogue of prostaglandin F2α) that lowers the pressure by increasing the outflow of aqueous fluid from the eyes through the uvealsclearal tract. Latanoprost is an isopropyl ester prodrug, meaning it is inactive until it is hydrolyzed by esterases in the cornea to the biologically active acid. Latanoprost, in pure form, is an oily liquid. For the convenience of use, it is supplied as 200mg / mL in ethanol. Synthetic Description Reference: Prévost S, Thai K, Schützenmeister N, Coulthard G, Erb W, Aggarwal VK. Synthesis of prostaglandin analogues, latanoprost and bimatoprost, using organocatalysis via a key bicyclic enal intermediate. Org Lett. 2015 Feb 6;17(3):504-7. doi: 10.1021/ol503520f. Epub 2015 Jan 12. PubMed PMID: 25582321. Synthetic Description Reference: Giuseppe Zanoni, Alessandro D’Alfonso, Alessio Porta, Lazzaro Feliciani, Steven P. Nolan, Giovanni Vidari. The Meyer–Schuster rearrangement: a new synthetic strategy leading to prostaglandins and their drug analogs, Bimatoprost and Latanoprost, Tetrahedron, Volume 66, Issue 38, 2010, Pages 7472-7478, ISSN 0040-4020, https://doi.org/10.1016/j.tet.2010.07.069. Synthetic Description Reference: Martynow, J. G., Jóźwik, J. , Szelejewski, W. , Achmatowicz, O. , Kutner, A. , Wiśniewski, K. , Winiarski, J. , Zegrocka‐Stendel, O. and Gołębiewski, P. (2007), A New Synthetic Approach to High‐Purity (15R)‐Latanoprost. Eur. J. Org. Chem., 2007: 689-703. doi:10.1002/ejoc.200600749 Synthetic Description Reference: Kawauchi G, Umemiya S, Taniguchi T, Monde K, Hayashi Y. Enantio- and Diastereoselective Synthesis of Latanoprost using an Organocatalyst. Chemistry. 2018 Jun 12;24(33):8409-8414. doi: 10.1002/chem.201800829. Epub 2018 May 22. PubMed PMID: 29603816. Synthetic Description Reference: VIJENDHAR, K & SRINIVAS, B & Boodida, Sathyanarayana. (2015). A Facile and Efficient Synthesis of (15R)-Latanoprost from Chiral Precursor Corey Lactone Diol. Journal of Chemical Sciences. 127. 10.1007/s12039-015-0963-2. Synthetic Description Reference: Achmatowicz, Osman. (2006). A novel method of synthesis of latanoprost. Przemysl Chemiczny. 85. 302-305. Synthetic Description Reference: Clissold, Derek Wyndham; Craig, Stuart Wilbert; Gadikota, Rajendrakumar Reddy; He, Min; Jurayj, Jurjus Fayez; Kazerani, Shahrokh; Rannala, Erwin; Sharma, Pradeep Kumar. Process for the synthesis of prostaglandin derivatives and intermediates. WO 2005058812. (Assignee Johnson Matthey Public Limited Company, UK) Synthetic Description Reference: Chambournier, Gilles; Kornilov, Andriy; Mahmoud, Hussein M.; Vesely, Ivan; Barrett, Stephen Douglas. Process for the preparation of F-series prostaglandins. WO 2011046569. (Assignee Cayman Chemical Company, USA) Synthetic Description Reference: Aggarwal, Varinder Kumar; Coulthard, Mark Graeme; Erb, William. Process for making a prostaglandin or a prostaglandin analog using a compound. WO 2013186550. (Assignee University of Bristol, UK) Synthetic Description Reference: Mariani, Edoardo; Orru', Gianmauro; Montorsi, Mauro; Andriolo, Erika; Bandini, Marco; Contento, Michele; Tolomelli, Alessandra. Process for the synthesis of prostaglandins and intermediates thereof. EP 2495235. (Assignee Newchem S.p.A., Italy)

• ROUTE 1



Reference: Prévost S, Thai K, Schützenmeister N, Coulthard G, Erb W, Aggarwal VK. Synthesis of prostaglandin analogues, latanoprost and bimatoprost, using organocatalysis via a key bicyclic enal intermediate. Org Lett. 2015 Feb 6;17(3):504-7. doi: 10.1021/ol503520f. Epub 2015 Jan 12. PubMed PMID: 25582321.

• ROUTE 2



Reference: Giuseppe Zanoni, Alessandro D’Alfonso, Alessio Porta, Lazzaro Feliciani, Steven P. Nolan, Giovanni Vidari. The Meyer–Schuster rearrangement: a new synthetic strategy leading to prostaglandins and their drug analogs, Bimatoprost and Latanoprost, Tetrahedron, Volume 66, Issue 38, 2010, Pages 7472-7478, ISSN 0040-4020, https://doi.org/10.1016/j.tet.2010.07.069.

• ROUTE 3



Reference: Martynow, J. G., Jóźwik, J. , Szelejewski, W. , Achmatowicz, O. , Kutner, A. , Wiśniewski, K. , Winiarski, J. , Zegrocka‐Stendel, O. and Gołębiewski, P. (2007), A New Synthetic Approach to High‐Purity (15R)‐Latanoprost. Eur. J. Org. Chem., 2007: 689-703. doi:10.1002/ejoc.200600749

• ROUTE 4



Reference: Kawauchi G, Umemiya S, Taniguchi T, Monde K, Hayashi Y. Enantio- and Diastereoselective Synthesis of Latanoprost using an Organocatalyst. Chemistry. 2018 Jun 12;24(33):8409-8414. doi: 10.1002/chem.201800829. Epub 2018 May 22. PubMed PMID: 29603816.

• ROUTE 5



Reference: VIJENDHAR, K & SRINIVAS, B & Boodida, Sathyanarayana. (2015). A Facile and Efficient Synthesis of (15R)-Latanoprost from Chiral Precursor Corey Lactone Diol. Journal of Chemical Sciences. 127. 10.1007/s12039-015-0963-2.

• ROUTE 6



Reference: Achmatowicz, Osman. (2006). A novel method of synthesis of latanoprost. Przemysl Chemiczny. 85. 302-305.

• ROUTE 7



Reference: Clissold, Derek Wyndham; Craig, Stuart Wilbert; Gadikota, Rajendrakumar Reddy; He, Min; Jurayj, Jurjus Fayez; Kazerani, Shahrokh; Rannala, Erwin; Sharma, Pradeep Kumar. Process for the synthesis of prostaglandin derivatives and intermediates. WO 2005058812. (Assignee Johnson Matthey Public Limited Company, UK)

• ROUTE 8



Reference: Chambournier, Gilles; Kornilov, Andriy; Mahmoud, Hussein M.; Vesely, Ivan; Barrett, Stephen Douglas. Process for the preparation of F-series prostaglandins. WO 2011046569. (Assignee Cayman Chemical Company, USA)

• ROUTE 9



Reference: Aggarwal, Varinder Kumar; Coulthard, Mark Graeme; Erb, William. Process for making a prostaglandin or a prostaglandin analog using a compound. WO 2013186550. (Assignee University of Bristol, UK)

• ROUTE 10



Reference: Mariani, Edoardo; Orru', Gianmauro; Montorsi, Mauro; Andriolo, Erika; Bandini, Marco; Contento, Michele; Tolomelli, Alessandra. Process for the synthesis of prostaglandins and intermediates thereof. EP 2495235. (Assignee Newchem S.p.A., Italy)