Designing the Molybdopterin Core through Regioselective Coupling of Building Blocks

Abstract

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 (1)H and (13)C 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.

Scorpionate Complexes as Models for Molybdenum Enzymes

“…Pterin‐Mo chemistry has been a topic of interest since 1982, when the structure of MPT was proposed by Rajagopalan and co‐workers . Progress in this difficult area has been slow and hard‐won but the total syntheses of MPT and the Mo‐cofactor (Moco) are advancing . Scorpionate ligands are playing their part in the stabilization of Mo‐pterin complexes, permitting the investigation of their structures, properties and behavior.…”

Synthesis, Redox and Spectroscopic Properties of Pterin of Molybdenum Cofactors

“…A similar nucleophilic attack occurs between the remaining amino and carbonyl groups resulting in pyrazine formation and the dehydration of two equivalents of water. The asymmetric nature of pyrimidine can produce a mixture of isomers which is dependent on the reactivity of participating amino and carbonyl moieties [ 20 ]. The amine at C5 of the pyrimidine is generally more nucleophilic and will attack the more electrophilic carbonyl moiety.…”

“…Adding NaHSO 3 helps to neutralize the sulfate and free the C5 amine on the pyrimidine for nucleophilic attack and produce the 6- substituted isomer. Similar reactions performed with an analogous diketo ester were unable to separate 6- and 7- pterin isomers via sulfite adduct precipitation [ 20 ], which suggests this method of isolation to be system specific. Pyranopterin synthesis with Na 2 SO 3 ·7H 2 O has also been utilized in a synthetic procedure to realize a dithiolene protected molybdopterin analogue of dephospho Form A, an oxidative degradation product of molybdenum cofactor [ 25 ].…”

Synthesis of α,β‐Dicarbonylhydrazones by Aerobic Manganese‐Catalysed Oxidation

“…On the other hand, the oxidation of a methylene group α to a carbonyl group to form vicinal dicarbonyl compounds is an important transformation which has many applications in organic synthesis as building blocks for the synthesis of bioactive molecules, especially those containing heterocycles . Conventional reagents for accomplishing this transformation, including strong oxidants such as selenium oxide, 2‐iodoxybenzoic acid (IBX), Dess‐Martin reagent or cerium(IV) salts, often lead to further oxidation or side reactions because of the strong reaction conditions employed.…”