Unambiguous determination of conformation and relative configuration of a multiple stereo-centre molecule Rifamycin-S by using scaled residual dipolar couplings: A case study

Abstract

Residual dipolar couplings (RDC) as additional orientational constraints offer a powerful means of determining molecular structures compared to the conventional (3JHH+NOE) based analysis. The recent advent of cross-linked polymer gel alignment media that are compatible for organic solvents has added further impetus to the RDC-enhanced NMR spectroscopy of small molecules, for precise structural elucidations. However, optimum strength of alignment for molecules dissolved in suitable anisotropic media is crucial for unambiguous measurement of RDCs. In contrast to the mechanical and chemical methods that are in practice, herein we exploit strain-induced fixation of alignment of PDMS/CDCl3 gels and conceptually known variable-angle assisted scaling strategies for tuning optimum range of alignment, thereby to record unambiguous one-bond C–H RDCs as well as the corresponding JCH scalar couplings in a model multiple-stereo centre molecule, Rifamycin-S. The analysis aided by the refined RDCs thus obtained, could single-out the exact conformation as well as relative configuration of Rifamycin-S, from its 256 configurational possibilities.