Structure and Conformation of Novel BODIPY Ugi Adducts.

Two novel BODIPY-Ugi (boron dipyrromethene) adducts exhibit peculiar room temperature (T=20 °C) H-1 NMR spectra in that several protons located at the aromatic aniline-type ring are lost in the baseline. This observation revealed the existence of a dynamic conformational process where rotation around the C-N bond is hindered. Variable-temperature H-1 and C-13 NMR spectroscopic analysis confirmed this conclusion; that is, low-temperature spectra show distinct signals for all four aromatic protons below coalescence, whereas average signals are recorded above coalescence (T=+120 °C). Particularly interesting was the rather large difference in chemical shifts for the ortho protons below coalescence, Δδ=1.45 ppm, which was explained based on DFT computational analysis. Indeed, the calculated lowest-energy gas-phase conformation of the BODIPY Ugi adducts locates one half of the aniline-type ring in the shielding anisotropic cone of the bridge phenyl ring in the BODIPY segment. This is in contrast to the solid-state conformation established by X-ray diffraction analysis that shows a nearly parallel arrangement of the aromatic rings, probably induced by crystal packing forces.

Mechanoenzymology in the Kinetic Resolution of ß-Blockers: Propranolol as a Case Study.

Recent advances in biotechnology, protein engineering, and enzymatic immobilization have made it possible to carry out biocatalytic transformations through alternative non-conventional activation strategies. In particular, mechanoenzymology (i.e., the use of the mechanical force produced by milling or grinding to activate a biotransformation) has become a new area in so-called "green chemistry", reshaping key fundaments of biocatalysis and leading to the exploration of enzymatic transformations under more sustainable conditions. Significantly, numerous chiral active pharmaceutical ingredients have been synthesized via mechanoenzymatic methods, boosting the use of biocatalysis in the synthesis of chiral drugs. In this regard and aiming to widen the scope of the young field of mechanoenzymology, a dual kinetic resolution of propranolol precursors was explored. The biocatalytic methodology mediated by Candida antarctica Lipase B (CALB) and activated by mechanical force allowed the isolation of both enantiomeric precursors of propranolol with high enantiomeric excess (up to 99% ee), complete conversion (c = 50%), and excellent enantiodifferentiation (E > 300). Moreover, the enantiomerically pure products were used to synthesize both enantiomers of the ß-blocker propranolol with high enantiopurity.