Hydrolase\u2013like catalysis and structural resolution of natural products by a metal\u2013organic framework

Marta Mon,Emilio Pardo,Donatella Armentano,Antonio Leyva-Pérez,Rosaria Bruno,Sergio Sanz-Navarro,Mario Prejanò,Jesús Ferrando-Soria,Tiziana Marino,Cristina Negro,Leonardo Di Donna,Lucia Bartella

doi:10.1038/s41467-020-16699-3

Abstract

The exact chemical structure of non–crystallising natural products is still one of the main challenges in Natural Sciences. Despite tremendous advances in total synthesis, the absolute structural determination of a myriad of natural products with very sensitive chemical functionalities remains undone. Here, we show that a metal–organic framework (MOF) with alcohol–containing arms and adsorbed water, enables selective hydrolysis of glycosyl bonds, supramolecular order with the so–formed chiral fragments and absolute determination of the organic structure by single–crystal X–ray crystallography in a single operation. This combined strategy based on a biomimetic, cheap, robust and multigram available solid catalyst opens the door to determine the absolute configuration of ketal compounds regardless degradation sensitiveness, and also to design extremely–mild metal–free solid–catalysed processes without formal acid protons.

Highlights

The exact chemical structure of non–crystallising natural products is still one of the main challenges in Natural Sciences
We report that a previously reported[30,31,34] highly robust crystalline metal–organic framework (MOF)-derived from the natural amino acid Lserine and whose micropores are densely decorated with methyl alcohol groups is capable to accommodate relatively big natural products, and performs, in a single operation, ketal deprotection and structural determination of sugars[1] and flavonoids of known and unknown absolute configuration
Isostructural MOF alamox (3) of formula {CaIICuII6[(S,S)-alamox]3(OH)2(H2O)}. 32H2O (where alamox = bis[(S)-alanine]oxalyl diamide) without alcohol but only methyl pending groups was used for comparison

Summary

Introduction

We show that a metal–organic framework (MOF) with alcohol–containing arms and adsorbed water, enables selective hydrolysis of glycosyl bonds, supramolecular order with the so–formed chiral fragments and absolute determination of the organic structure by single–crystal X–ray crystallography in a single operation This combined strategy based on a biomimetic, cheap, robust and multigram available solid catalyst opens the door to determine the absolute configuration of ketal compounds regardless degradation sensitiveness, and to design extremely–mild metal–free solid–catalysed processes without formal acid protons. After selectively incorporating, untouched, the fragment of unknown chirality into the MOF, the solid structure is resolved by SCXRD to give the absolute configuration of the adsorbed organic fragment (Fig. 1a) and, of the natural product

Methods

Results

Conclusion