β-Ketophosphonates with Pentalenofuran Scaffolds Linked to the Ketone Group for the Synthesis of Prostaglandin Analogs
Open Access
- 24 June 2021
- journal article
- research article
- Published by MDPI AG in International Journal of Molecular Sciences
- Vol. 22 (13), 6787
- https://doi.org/10.3390/ijms22136787
Abstract
β-Ketophosphonates with pentalenofurane fragments linked to the keto group were synthesized. The bulky pentalenofurane skeleton is expected to introduce more hindrance in the prostaglandin analogues of type III, greater than that obtained with the bicyclo[3.3.0]oct(a)ene fragments of prostaglandin analogues I and II, to slow down (retard) the inactivation of the prostaglandin analogues by oxidation of 15α-OH to the 15-keto group via the 15-PGDH pathway. Their synthesis was performed by a sequence of three high yield reactions, starting from the pentalenofurane alcohols 2, oxidation of alcohols to acids 3, esterification of acids 3 to methyl esters 4 and reaction of the esters 4 with lithium salt of dimethyl methanephosphonate at low temperature. The secondary compounds 6b and 6c were formed in small amounts in the oxidation reactions of 2b and 2c, and the NMR spectroscopy showed that their structure is that of an ester of the acid with the starting alcohol. Their molecular structures were confirmed by single crystal X-ray determination method for 6c and XRPD powder method for 6b.Funding Information
- University of Bucharest (UniRem project no. 244 and the contract CNFIS-FDI-2020-0355.)
- Ministerul Cercetării şi Inovării (grant Orizont-2000, 45/1999/1)
This publication has 19 references indexed in Scilit:
- OLEX2: a complete structure solution, refinement and analysis programJournal of Applied Crystallography, 2009
- A short history of SHELXActa Crystallographica Section A Foundations of Crystallography, 2007
- Taprostene SodiumCardiovascular Drug Reviews, 1993
- Synthesis of therapeutically useful prostaglandin and prostacyclin analogsChemical Reviews, 1993
- Stereocontrolled synthesis of exocyclic olefins using arene tricarbonyl chromium complex-catalyzed hydrogenation. I. Efficient synthesis of carbacyclin and its analogs.CHEMICAL & PHARMACEUTICAL BULLETIN, 1991
- A highly convergent synthesis of mexiprestil: 16(R) 16-methoxy 16-methyl PGE1 methyl esterTetrahedron Letters, 1988
- Potent prostacyclin analogs based on the bicyclo[4.2.0]octane ring systemThe Journal of Organic Chemistry, 1987
- Total synthesis of a novel antiulcer agent via a modification of the intramolecular Wadsworth-Emmons-Wittig reactionJournal of the American Chemical Society, 1985
- A new stable prostacyclin mimic, 7-oxo-PGI2Journal of Medicinal Chemistry, 1982
- Total synthesis of 15-methylprostaglandinsJournal of the American Chemical Society, 1974