Absolute Configuration Assignment to Chiral Natural Products by Biphenyl Chiroptical Probes: The Case of the Phytotoxins Colletochlorin A and Agropyrenol

Ernesto Santoro,Patrizia Scafato,Stefano Superchi,Sandra Belviso,Marco Masi,Stefania Vergura,Antonio Evidente

doi:10.1021/acs.jnatprod.9b01068

Ernesto Santoro, Patrizia Scafato + Show 5 more

Open Access

https://doi.org/10.1021/acs.jnatprod.9b01068

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Abstract

The application of flexible biphenyls as chiroptical probes for the absolute configuration assignment to chiral natural products is described. The method is straightforward and reliable and can be applied to conformationally mobile and ECD silent compounds, not treatable by computational analysis of chiroptical data. By this approach, the (6′R) absolute configuration of the phytotoxin colletochlorin A (1) was confirmed, while the absolute configuration of the phytotoxin agropyrenol (2), previously assigned by the NMR Mosher method, was revised and assigned as (3′S,4′S). Moreover, with the biphenyl method the configurational assignment can be obtained simply by the sign of a diagnostic Cotton effect at 250 nm in the ECD spectrum, thus allowing application without the need of advanced knowledge of chiroptical spectroscopy and computational protocols.

Highlights

The application of flexible biphenyls as chiroptical probes for the absolute configuration assignment to chiral natural products is described
Chiral diols and polyols are extremely common among natural products; the most immediate examples are carbohydrates, and many natural products isolated from plants, fungi, terrestrial and marine organisms,[31] possess di- and polyhydroxylated moieties.[32,33]
The former are mainly based on the electronic circular dichroism (ECD) data analysis of diol metal complexes,[34] while the latter are based on the exciton chirality method,[35,36] or quantum mechanical computations of chiroptical data.[37]

Summary

Introduction

The application of flexible biphenyls as chiroptical probes for the absolute configuration assignment to chiral natural products is described. This significantly increased the use of computational methodologies in structural analysis,[14,15] making this approach the method of choice for reliable AC assignments in solution.[16] despite the hundreds of successful applications reported,[17,18] this approach still remains difficult to apply for highly flexible molecules, displaying many populated conformers and/or giving rise to low chiroptical responses, a common situation encountered in complex natural products.

Results

Conclusion