Aplisulfamines, New Sulfoxide-Containing Metabolites from an Aplidium Tunicate: Absolute Stereochemistry at Chiral Sulfur and Carbon Atoms Assigned Through an Original Combination of Spectroscopic and Computational Methods

Anna Aiello,Marialuisa Menna,Ernesto Fattorusso,Rocco Vitalone,Concetta Imperatore,Paolo Luciano

doi:10.3390/md10010051

Abstract

Two new sulfoxide-containing metabolites, aplisulfamines A (1) and B (2), have been isolated from an Aplidium sp. collected in the Bay of Naples. Their planar structure and geometry of a double bond were readily determined by using standard methods, mainly NMR spectroscopy. An original approach was used to assign the absolute configuration at the three contiguous chiral centers present in the structures of both aplisulfamines, two at carbon and one at sulfur. This involved Electronic Circular Dichroism (ECD) studies, J-based configuration analysis and Density Functional Theory (DFT) calculations and represents an interesting integration of modern techniques in stereoanalysis, which could contribute to the enhancement of theoretical protocols recently applied to solve stereochemical aspects in structure elucidation.

Highlights

The occurrence of sulfoxides in nature is limited, being confined mostly to peptide derivatives containing methionine- or β,β-dimethylmethionine S-oxides [1,2], podolactones [3], compounds from onions and other Allium species [4], as well as few marine secondary metabolites [5,6,7,8]
Through a DFT (Density Functional Theory) approach we have identified a series of conformers resulting from rotation around the S(O)-C2 bond in models A and B
The interesting combination of spectroscopic and computational methods used to assign the absolute stereochemistry of aplisulfamines and, the original approach we used to assign the relative configuration of an acyclic system composed by an asymmetric carbon linked to a chiral sulfoxide, contribute to the enhancement of theoretical protocols recently applied to solve stereochemical aspects in structure elucidation

Summary

Introduction

The occurrence of sulfoxides in nature is limited, being confined mostly to peptide derivatives containing methionine- or β,β-dimethylmethionine S-oxides [1,2], podolactones [3], compounds from onions and other Allium species [4], as well as few marine secondary metabolites [5,6,7,8]. As a part of our ongoing search for new and/or bioactive metabolites from Mediterranean ascidians, two novel natural sulfoxides, aplisulfamines A (1) and B (2), have been isolated from the tunicate Aplidium sp. An original approach was used to solve the absolute configuration at the three contiguous chiral centers of the molecules, two at carbon and one at sulfur. This represented an interesting integration of modern techniques in stereoanalysis and involved ECD studies, J-based configuration analysis and Density Functional Theory (DFT) calculations. Aplisulfamines A and B were tested for their cytotoxic and/or antiproliferative effects on cancer cells as well as for their antimicrobic properties; in both cases, the new metabolites did not show significant activity

Results and Discussion

General Experimental Procedures

Computational Details

Conclusions