Determination of the Absolute Configuration of Ballonigrin Lactone A Using Density Functional Theory Calculations

We report the determination of the absolute configuration of a diterpenoid, namely, ballonigrin lactone A (BLA), by comparison of the computed optical rotations, [alpha]D, of its two diastereomers using density functional theory (DFT) calculations to the experimental [alpha]D value of +22.4. One of the diastereomers having configurations 4S, 5R, 6S, 10S, 15S was named "alpha-BLA," and the other one with configuration 4S, 5R, 6S, 10S, 15R was called ",g-BLA". Six conformers for each diastereomer (alpha-BLA and ,g-BLA) of BLA were identified through their conformational analysis. [alpha]D values of these six conformations for each diastereomer were calculated using DFT at the mPW1PW91/6-311G(d,p)/SMDChloroform level of theory, leading to the conformationally averaged [alpha]D values of -96.8 for alpha-BLA and +65.1 for ,g-BLA. Thus, it was found that the experimental [alpha]D value of +22.4 was of 4S, 5R, 6S, 10S, 15R, i.e., ,g-BLA. Experimental and computed nuclear magnetic resonance (NMR) data were also compared, and this comparison was in accordance with the conclusion drawn from the comparison of [alpha]D values. Finally, the results were augmented with the calculation of the DP4 analysis, and the probability obtained also endorsed our earlier calculations.