Molecular modeling, NMR spectroscopy, and conformational analysis of 3′,4′‐anhydrovinblastine

Abstract

The assignment of the proton spectrum of 3′,4′‐anhydrovinblastine is reported. Assignments are made for several protons for which only approximate assignments were available previously. Homonuclear TOCSY and ROESY spectra were utilized in conjunction with HMQC and HMBC spectra in making the assignment. Correlations in the ROESY spectrum suggested a preferred conformation of the cleavamine (upper) portion of 3′,4′‐anhydrovinblastine in which the 21‐methyl of the 20/21 ethyl group of the vindo‐line (lower) portion is in proximity to the H14′ and 16′‐NH resonances of the cleavamine. In a Monte Carlo search, the global minimal energy structure was oriented with the 16‐methoxyl group oriented toward the H14′ and 16′‐NII resonances. Two other structures, the second and tenth lowest in energy, 0,2 kJ and 8 kJ higher in energy, respectively, brought the 21‐methyl group in proximity to the H14′ and 16′‐NH resonances in a fashion consistent with the ROESY data. The preferred solution conformation of 3′,4′‐anhy‐drovinblastine is consistent with the reported solution conformation of vinblastine.

Structure elucidation of indole–indoline type alkaloids: A retrospective account from the point of view of current NMR and MS technology

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“…Continuing with these investigations, an analysis of the solution behaviour of AVLB and its borane complex was conducted by Szántay et al [84] and by Andrews and co-workers [85]. In the former paper, an NMR investigation including the use of 1 H 1 H NOE measurements in the presence of 11 B decoupling were performed together with COSY and 13 C 1 H heterocorrelation methods for AVLB and its borane complex using a 400 MHz spectrometer.…”

Chemical structural and thermodynamic study of anthocyanins family in viewpoint of electron transfer

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Behavior of the Chemicals in the Brain in Viewpoint of Learning Cognition by a Theoretical Simulation

“…It doesn't always need random numbers to use deterministic, pseudo-random sequences, making it easy to test and re-run simulations [49]. In Monte Carlo (MC) methods, a sequence of points in phase space is generated from an initial geometry by adding a random "kick" to the coordinates of a randomly chosen particle (atom or molecule).…”

“…The new configuration is accepted if the energy decreases and with a probability of e−∆E/kT if the energy increases. This Metropolis procedure ensures that the configurations in the ensemble obey a Boltzmann distribution, and the possibility of accepting higher energy configurations allows MC methods to climb uphill and escape from a local minimum [49].…”