Designing the Molybdopterin Core through Regioselective Coupling of Building Blocks

• Published in: Chemistry : a European journal Vol. 21; no. 47; pp. 17057 - 17072
• Main Authors: Pimkov, Igor V., Serli-Mitasev, Barbara, Peterson, Antoinette A., Ratvasky, Stephen C., Hammann, Bernd, Basu, Partha
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 16-11-2015; WILEY‐VCH Verlag; Wiley Subscription Services, Inc
• Subjects: bioinorganic chemistry; Chemistry; Condensing; Derivatives; heterocyclic compounds; Infrared spectroscopy; Joining; Mass Spectrometry; Molecular Structure; Molybdenum - chemistry; natural products; organic ligands; Phenylenediamines - chemistry; Physical properties; Precursors; Pterins - chemical synthesis; Pterins - chemistry; Strategy; synthetic methods; natural products; organic ligands; heterocyclic compounds; synthetic methods; bioinorganic chemistry
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201502845

Molybdopterin is an essential cofactor for all forms of life. The cofactor is composed of a pterin moiety appended to a dithiolene‐functionalized pyran ring, and through the dithiolene moiety it binds metal ions. Different synthetic strategies for dithiolene‐functionalized pyran precursors that have been designed and synthesized are discussed. These precursors also harbor 1,2‐diketone or osone functionality that has been condensed with 1,2‐diaminobenzene or other heterocycles resulting in several quinoxaline or pterin derivatives. Use of additives improves the regioselectivity of the complexes. The molecules have been characterized by 1H and 13C NMR and IR spectroscopies, as well as by mass spectrometry. In addition, several compounds have been crystallographically characterized. The geometries of the synthesized molecules are more planar than the geometry of the cofactor found in proteins.
It’s time for a molybdopterin core! The design and syntheses of several dithiolene‐functionalized pyran derivatives are described. This approach allows the preparation of compounds with the desired functionality. The synthesized compounds have been characterized, and their physical properties provide an avenue for comparison with the native cofactor (R=reactant, P=product).