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, [α], of its two diastereomers using density functional theory (DFT) calculations to the experimental [α] value of +22.4. One of the diastereomers having configurations 4S, 5R, 6S, 10S, 15S was named "α-BLA," and the other one with configuration 4S, 5R, 6S, 10S, 15R was called "β-BLA". Six conformers for each diastereomer (α-BLA and β-BLA) of BLA were identified through their conformational analysis. [α] values of these six conformations for each diastereomer were calculated using DFT at the mPW1PW91/6-311G(d,p)/SMD level of theory, leading to the conformationally averaged [α] values of -96.8 for α-BLA and +65.1 for β-BLA. Thus, it was found that the experimental [α] value of +22.4 was of 4S, 5R, 6S, 10S, 15R, i.e., β-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 [α] values. Finally, the results were augmented with the calculation of the DP4 analysis, and the probability obtained also endorsed our earlier calculations.