Jörg Fleischhauer

MD‐based CD calculations for the assignment of the absolute axial configuration of the naphthylisoquinoline alkaloid dioncophylline A

The circular dichroism (CD) of the biaryl alkaloid dioncophylline A (2) was investigated by CD calculations; the structures were generated by molecular dynamics (MD) simulations using the force field CVFF. From these structures the CD spectra were calculated with the semiempirical method CNDO/2S. Summing up the single CD spectra yielded the final spectrum. In contrast to our earlier method based on the Boltzmann weighting, the MD‐assisted approach permitted to assign the flexible biaryl axis of dioncophylline A (2), which is found to be P.

CALCULATION OF THE CIRCULAR DICHROISM SPECTRUM OF CYCLO-(L-TYR-L-TYR) BASED ON A MOLECULAR DYNAMICS SIMULATION

Theoretical calculations of CD spectra have generally assumed a single conformation, or a small number of conformers with Boltzmann averaging. Solvent effects on both the conformation and the CD have been neglected. In this work, we have calculated the CD spectrum of cyclo(L-Tyr-L-Tyr) in aqueous solution, taking dynamics and solvation into account. Starting geometries with chi 1 approximately 300 degrees or 60 degrees for both Tyr side chains were derived from MNDO/MOPAC, followed by energy minimization using GROMOS. After addition of 368 water molecules, the system was simulated for 1000 ps at 300 K using GROMOS. In addition to the starting conformer, two other conformers were observed during each simulation. However, each trajectory gave a distinct set of conformers. Rotational strengths were calculated for the cyclic dipeptide at each ps along the trajectories, using the matrix method. The CD spectra calculated from these rotational strengths were averaged over the trajectories. Agreement is very good for the strong negative band near 200 nm, while for the lower energy bands (near 230 and 280 nm), the signs are correct, but the magnitudes are too low. The spectrum calculated from a Boltzmann-weighted average over the in vacuo MNDO/MOPAC conformers was in poor agreement with experiment. Although the solvent did not significantly affect the rotational strength calculated for a given conformer, it is essential to include the solvent in the MD simulations because it affects the relative energies of the conformers and promotes transitions among them.

Pigments from the Puffball Calvatia rubro-flava − Isolation, Structural Elucidation and Synthesis

The orange pigment rubroflavin (1) from the dried fruit bodies of Calvatia rubro-flava (Lycoperdaceae) owes its high optical rotation to a methanesulfinyl group directly attached to a 1,4-benzoquinone semicarbazone chromophore. Rubroflavin is present in fresh fungi in its leuco form 4, which is easily oxidized to 1. Thermal fragmentation of 1 yields (−)-3-methanesulfinyl-5-(methylthio)phenol (6), whose configuration was assigned as (S) by quantum mechanical calculations. This result is supported by CD comparison of 6 with (S)-4-(methanesulfinyl)toluene, and the synthesis of (S)-1 from esters of deoxyrubroflavin (8) by stereoselective sulfoxidation. In the same manner, optically active (S,S)-oxyrubroflavin (2) and (S)-craniformin (3) were obtained. NMR measurements in different solvents indicate that 1 and the related 1,4-benzoquinone semicarbazones are in equilibrium with their azophenol tautomers.

Lipase catalyzed resolution of α-hydroxymethyl sulfones. Determination of absolute configuration by semiempirical calculation of CD spectra and verification by X-ray structure analysis

Abstract The Candida antarctica lipase catalyzed esterification of the hydroxymethyl sulfones rac- 1a and rac- 1b led to the isolation of ent- 1a (92% ee) and 1b (≥99% ee), respectively. The acyloxymethyl sulfone ent- 7a (≥99% ee) was obtained by the Candida antarctica lipase catalyzed hydrolysis of rac- 7a . Not only Candida antarctica lipase but also Pseudomonas cepacia lipase showed the opposite enantiomer differentiation in the esterification of the methyl substituted alcohol rac- 1a and the benzyl substituted alcohol rac- 1b . The absolute configuration of ent- 1a and 1b was determined by measurement of their circular dichroism and the calculation of the CD spectra of 1a and 1b by semiempirical methods. The configurational assignment was verified by X-ray structure analysis of 1b and ent- 7a .

Determination of the Absolute Configuration of Rubroflavin by Comparison of Measured and Calculated CD Spectra of its Thermolysis Product 3-Methanesulfinyl-5-Methylmercaptophenol

The absolute configuration of rubroflavin has been determined indirectly by comparison of the measured and the calculated CD spectrum of its thermal decomposition product 3-methanesulfinyl-5-methylmercaptophenol. Performing geometry optimizations at the HF/6-31+G* level we found fifteen local minima for the (R)-isomer of 3-methanesulfinyl-5-methylmercaptophenol. The CD spectrum of the compound was then obtained as a superposition of the Boltzmann-weighted spectra for each structure calculated with the non-empirical CIS method. The corresponding Boltzmann factors have been calculated employing the relative energies of these minima determined at the ZPE + MP2/6-31+G*//HF/6-31+G* level of ab initio theory. Comparing the signs of the observed and calculated longest wave length Cotton effect we assign an absolute configuration to the thermolysis product. Since additional calculations revealed that the tricoordinate sulfur atom in rubroflavin and in its decomposition product is configurationally stable under the conditions of thermolysis we conclude that the absolute configuation at the corresponding sulfur atom of rubroflavin is the same.

AB Initio Calculations on Sulfonylmethyl Anions

Abstract The role of negative hyperconjugation in the title compounds is elucidated by the results of quantum chemical ab initio calculations.

THE ENERGETICALLY PREFERRED ORIENTATION OF THE HYDROXYL GROUP IN CYCLOHEXANOL. AB INITIO AND FORCE FIELD CALCULATIONS

Abstract Quantum chemical calculations on four isomers of cyclohexanol in its chair form were performed in order to determine the energetically preferred orientation of the hydroxyl group. Basis sets of different size were employed to study the influence of diffuse and polarization functions. To elucidate the role of correlation effects the calculations were carried out at both the Hartree-Fock (HF) and correlated (MP2, MP4) level of ab initio theory. The results of all calculations agree that at a maximum value of 2 kcal mol −1 , the energy difference between all four isomers is small. Depending on the quality of the basis set and on the inclusion of correlation energy, the most stable isomer has its hydroxyl group either in an axial or equatorial position. Our combined results converge to the point that three isomers (two equatorial and one axial) are quite similar in energy. These conformers are separated from the least stable species (axial) by an energy difference of 0.9–1.6 kcal mol −1 .