Über Pterinchemie. 77. Mitteilung)Das (6R,S)‐5‐Formyl‐6‐methyl‐5,6,7,8‐tetrahydropterin: Synthese, chemische und physikalisch‐chemische Eigenschaften

Abstract

(6R,S)‐5‐Formyl‐6‐methyl‐5,6,7,8‐tetrahydropterine: Synthesis, Chemical and Physico‐chemical Properties (6R, S)‐5‐Formyl‐6‐methyl‐5,6,7,8‐tetrahydropterine (III), a model substance for the biologically important 6‐substituted 5‐formyl‐5,6,7,8‐tetrahydropterines, was obtained for the first time by formylation of the corresponding tetrahydropterine with formic acid. Compound III, analogously to the other known 5‐acyltetrahydropterines, exists in solution (except in DMSO) as a mixture of two rotamers IIIa and IIIb. The two H‐C(7) in III have the same chemical shift and the same coupling constant to H‐C(6), giving rise to a A,A',X,C‐system. Conformational analysis of III, based on its 1H‐NMR,‐spectrum, shows that the methyl group is pseudo‐axial and the formyl group pseudo‐equatorial. Moreover, the H(X)‐C(6) bond lies nearly in the plane bisecting the C(6)‐C(7)‐H(A), C(6)‐C(7)‐H(A') dihedral angle; the C(6) and C(7) lie outside the N(5)‐C(4a)‐C(8a) plane and the tetrahydropyrazine cycle must be extremely strained, according to Dreiding models.

Hybrid Quantum and Classical Simulations of the Dihydrofolate Reductase Catalyzed Hydride Transfer Reaction on an Accurate Semi-Empirical Potential Energy Surface

“…As for the reduced equilibrium structures (6-Me-H 4 pterin and 6-Me-H 3 pterin – ), the pyrazine ring adopts a half-chair conformation, where C6 and C7 lie below and above the plane, respectively, in a staggered conformation with respect to each other, and the methyl group attached to C6 takes a pseudoequatorial position. These findings are in good agreement with 1 H NMR studies on tetrahydropterin derivatives (spin–spin coupling constants measurements). − A comparison of the crystal structure of 6-Me-H 3 pterin + and the computed geometry at the B3LYP/6-31G(2df,p) level is available in the Supporting Information.…”