Advanced NMR Strategies for Pharmaceutical Molecule Characterization and Structure Analysis

Dra. María Victoria Silva Elipe, Process Development Scientific Associate Director, will be leading an insightful conversation on Practical Measurements Strategy of Anisotropic RDC Data for Stereochemical Characterization of Molecules. Followed by Dr. Ikenna Ndukwe discussing Mnova CASE-3D Methodology and DFT Combine for Unambiguous Structure Analysis of AMGEN APIs. We will have Professor Armando Navarro-Vázquez, who will speak about StereoFitter. Practical multiparametric NMR stereochemical analysis and will provide some recommendations and novelties.

Practical Measurements Strategy of Anisotropic RDC Data for Stereochemical Characterization of Molecules

• Presented here is the practical measurement of residual dipolar couplings (RDCs) from J-resolved and J-scaled BIRD HSQCs using isotropic (DMSO-d6) and anisotropic media (poly-HEMA gel in DMSO-d6 in a compression device). The study applies the computer-assisted structure elucidation (CASE-3D) protocol implemented in Mestrenova software and tested against MMFF94 conformer structures and DFT chemical shift shielding for the diastereisomers of a natural product, artemisinin. Input files were created as combination of 13C chemical shifts and RDCs values to ensure satisfactory discrimination against the second ranked diastereomer.

Mnova CASE-3D Methodology and DFT Combine for Unambiguous Structure Analysis of AMGEN APIs

• As the molecular complexities of pharmacuetical APIs (active phamacuetical ingredients) continue to expand, it is imperative for analytical chemists to continually evolve or develop analytical methodologies that are robust to provide unambiguous structure identification. Orthogonal analytical methods, in combination with stereospecific synthetic steps, ensures that the chemical integrity of APIs in drug products delivered to patients are maintained. Molecular features that complicate structure analysis, including the presence of multiple distal stereocenteres and/or the presence of a macrocycle that often requires multiple synthetic steps, places enormous burden on traditional analytical approaches for structure elucidation. In this presentation, we will highlight the utilization of NMR and CASE-3D methods for unambiguous structure analysis of complex macrocycle APIs (in this example, six chiral centers).

StereoFitter. Practical multiparametric NMR stereochemical analysis. Recommendations and novelties.

• StereoFitter offers several computational strategies for conformational deconvolution of NMR properties. Practical application of these strategies that will be discussed in this webinar along with the presentation of new features for the analysis of J-couplings, chemical shifts and others.

Presenter: Dr. María Victoria Silva Elipe (Process Development Scientific Associate Director, NMR Leader at Amgen Attribute Science department in Process Development)

María supports drug development from early clinical to commercial for small molecules and hybrid modalities. With almost three decades of experience in the pharmaceutical industry, her work has focused on low/high field NMR for structure elucidation, reaction monitoring, quantitation, and TD-NMR applications. Her Ph.D. was in Natural Products Chemistry at the University of Málaga, Spain.

Presenter: Dr. Ikenna Ndukwe (Process Development Senior Scientist – Technology)

Dr. Ikenna Ndukwe obtained his Ph.D. from the University of Bristol, United Kingdom, where his thesis focused on NMR methodology development. His is currently a Process Development Senior Scientist – Technology at Amgen, Thousand Oaks, California, where he supports small molecule drug development from early stage clinical to comercial.

Presenter: Prof. Armando Navarro-Vázquez (Professor of Chemistry)

Prof. Armando Navarro-Vázquez obtained his PhD in the University of Santiago de Compostela. Currently he is a full professor at the University Federal de Pernambuco where he works in the development of computational methodologies and new materials applied to structure elucidation of organic compounds.