Polymorphism critically influences the solid-state properties of organic molecules, affecting stability, solubility, and functionality. We investigated the polymorphic behavior of enantiomerically pure (+)-(6aS,11aS)-medicarpin through combined experimental and computational analyses. Single-crystal X-ray diffraction revealed two distinct chiral polymorphs: the previously reported monoclinic P2₁ form and a newly identified orthorhombic P2₁2₁2₁ form with a fully chiral packing arrangement. The discovery of this previously unreported polymorph underscores the subtle yet decisive effects of solvent and conformational flexibility in directing crystallization. Detailed structural analysis reveals that, whereas the P2₁ form is only stabilized by a single dominant electrostatic interaction, the P2₁2₁2₁ form features a more complex network comprising C-H···π contacts, bifurcated C-H···O hydrogen bonds, and aromatic edge-to-face interactions. Further investigation of a functionalized p-nitrobenzoate derivative corroborates the critical influence of molecular substituents and crystallization conditions on packing motifs. Lattice energy DFT calculations confirm that each polymorph is stabilized by distinct electrostatic and dispersive interaction patterns, illustrating the complex energetic landscape of polymorph selection. Altogether, this work provides a framework for understanding and anticipating which polymorph is likely to form under specific solvent and crystallization conditions, offering insights for future strategies in materials design and guiding the pursuit of patentable crystalline forms in pharmaceutical applications.

Medicarpin, a natural pterocarpan phytoalexin, contributes to tree defense against microbial decay, particularly from the aggressive white-rot fungus Trametes versicolor, an ASTM standard for wood durability testing. To improve upon the inhibitory effect of medicarpin against this fungus (150 mg/L), eleven derivatives were synthesized and evaluated. The acetylated analog demonstrated superior activity, achieving complete growth inhibition at 100 mg/L. To establish a structure–activity relationship, molecular docking was performed on the copper cluster on fungal laccase, the primary oxidative enzyme of T. versicolor. The acetylated derivative bound the T1 copper site with a more favorable free energy (−8.5 kcal/mol) than the parent compound, exhibiting enhanced stabilizing interactions and a binding pose anchored closer to the trinuclear copper cluster (TNC). These results were corroborated by 80 ns molecular dynamics simulations, confirming complex stability and the persistence of key interactions. This study demonstrates that targeted chemical modification of natural phytoalexins can significantly improve their antifungal potency. The superior performance of the acetylated medicarpin derivative, linked to optimized binding at the laccase active site, establishes a clear structure–activity relationship and highlights the potential of such engineered compounds as leads for next-generation, bio-inspired wood preservatives.

The induction of chirality to obtain enantiopure products of high synthetic value is of great importance across various scientific fields, particularly in the medical area, as it has been demonstrated that the different enantiomers of drugs interact differently with biological receptors. In this context, asymmetric catalysis focuses on the design of catalysts that are easy to synthesize, capable of efficiently and enantioselectively forming C–C bonds, and suitable for reuse in multiple catalytic processes. This work describes the application of a Pd(II) complex coordinated with the R and S forms of proline in direct Aldol, Morita–Baylis–Hillman, and Heck coupling reactions. The catalytic system efficiently promoted the aldol reaction, achieving yields of 80–95%, excellent diastereoselectivities (1:69 syn/anti), and enantiomeric excesses greater than 99%. From a mechanistic perspective, the formation of a transition state is proposed in which a proline molecule generates an enamine that, upon coordination with the metal center, is stabilized through interaction with the intermediate’s double bond. Moreover, the study of the Morita–Baylis–Hillman and Heck coupling reactions highlights the versatility of this type of catalyst.