Application of Computational Chemical Shift Prediction Techniques to the Cereoanhydride Structure Problem-Carboxylate Complications.

Carla Saunders,Dean Tantillo

doi:10.3390/md15060171

Abstract

Despite the vast array of techniques available to modern-day chemists, structural misassignments still occur. These misassignments are often only realized upon attempted synthesis, when the spectra of synthesized products do not match previously reported spectra. This was the case with marine natural product cereoanhydride. The originally proposed 7-membered ring anhydride (1) was shown to be incorrect, although a likely precursor to the correct structure (2) in both its laboratory synthesis and biosynthesis. Herein, in addition to showing how NMR computations could have been used to arrive at the correct structure, we show that the conversion of 1 to 2 is indeed energetically viable, and we highlight complications in predicting NMR chemical shifts for molecules with acidic protons.

Highlights

The isolation and structural assignment of natural products remains a very active field, continuing to lead to the discovery of many important compounds
While computational methods for predicting 1 H and 13 C chemical shifts are well established [6,7,8,9,10], these methods do not work without fail
We are interested in cases where readily exchangeable protons affect 13 C chemical shifts, e.g., chemical shifts for carbons near to amines or carboxylic acids [11]

Summary

Introduction

The isolation and structural assignment of natural products remains a very active field, continuing to lead to the discovery of many important compounds. Computational chemistry, in particular NMR prediction using quantum chemical methods, can be used as a tool to facilitate confirmation, assignment, and reassignment of natural product structures [6,7,8,9,10] and can be used to focus laboratory experiments on correct structures. We are interested in cases where readily exchangeable protons affect 13 C chemical shifts, e.g., chemical shifts for carbons near to amines or carboxylic acids [11]. In such systems, NMR spectra are pH-sensitive, and such molecules tend to oligomerize, making spectral prediction difficult [6,12,13,14]

Methods

Results

Conclusion