Structure Validation of Complex Natural Products: Time to Change the Paradigm. What did Synthesis of Alstofolinine A Prove?

Abstract

Total synthesis has been an effective and broadly practiced approach for structure validation (or revision) of complex natural products. It appears that computational methods for structure elucidation are gradually becoming a better alternative, being faster and more reliable, as found in the case of alstofolinine A.

Quantum Mechanical–NMR-Aided Configuration and Conformation of Two Unreported Macrocycles Isolated from the Soft Coral Lobophytum sp.: Energy Calculations versus Coupling Constants

“…[4][5][6] Despite NMR and X-ray crystallography are the gold-standard techniques used for structure elucidation, computational methods are gradually becoming a faster and sometimes even more reliable alternative. 7,8 In our continuous effort to discover bioactive marine natural products from Chinese soft corals, [9][10][11] Lobophytum sp. was collected off the coast of Xisha Island, Hainan Province.…”

The DP5 probability, quantification and visualisation of structural uncertainty in single molecules

“…1 Many of those incorrectly assigned are only discovered after costly and time consuming total syntheses are completed revealing a discrepancy between the experimental and literature NMR data. 2–4…”

“…1 Many of those incorrectly assigned are only discovered aer costly and time consuming total syntheses are completed revealing a discrepancy between the experimental and literature NMR data. [2][3][4] Over the last two decades, many computational tools have been developed to aid the assignment of NMR spectra and elucidation of molecular structures. [5][6][7] Comparing experimental NMR shis with those calculated for a candidate structure using density functional theory (DFT) is now a well-established methodology and has been used to solve the structures of many molecules.…”

Stereochemical revision of xylogranatin F by GIAO and DU8+ NMR calculations

“…NMR calculations have become an increasingly useful and widely employed tool in both structural determination and revision of complicated molecules, especially in the context of natural products isolation and multistep synthesis (for reviews, see previous studies [1][2][3][4] ; for several notable examples using NMR calculations for structural revision, see previous works [5][6][7][8][9][10][11] ). Utilization of modern quantum chemical computations has the advantage of magnifying and quantifying subtle differences among similar structures (eg, diastereomers).…”