Synthesis 2015; 47(16): 2367-2376
DOI: 10.1055/s-0034-1381032
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© Georg Thieme Verlag Stuttgart · New York

Harnessing the Intrinsic Reactivity within the Aplysinopsin Series for the Synthesis of Intricate Dimers: Natural from Start to Finish

Adam Skiredj
a  Laboratoire de Pharmacognosie associé au CNRS, UMR 8076 BioCIS, LabEx LERMIT, Faculté de Pharmacie, Université Paris-Sud, 92296 Châtenay-Malabry, France   eMail: laurent.evanno@u-psud.fr   eMail: erwan.poupon@u-psud.fr
,
Mehdi A. Beniddir
a  Laboratoire de Pharmacognosie associé au CNRS, UMR 8076 BioCIS, LabEx LERMIT, Faculté de Pharmacie, Université Paris-Sud, 92296 Châtenay-Malabry, France   eMail: laurent.evanno@u-psud.fr   eMail: erwan.poupon@u-psud.fr
,
Delphine Joseph
a  Laboratoire de Pharmacognosie associé au CNRS, UMR 8076 BioCIS, LabEx LERMIT, Faculté de Pharmacie, Université Paris-Sud, 92296 Châtenay-Malabry, France   eMail: laurent.evanno@u-psud.fr   eMail: erwan.poupon@u-psud.fr
,
Guillaume Bernadat
b  Équipe ‘Molécules fluorées et chimie médicinale’, UMR 8076 BioCIS, LabEx LERMIT, Faculté de Pharmacie, Université Paris-Sud, 92296 Châtenay-Malabry, France
,
Laurent Evanno*
a  Laboratoire de Pharmacognosie associé au CNRS, UMR 8076 BioCIS, LabEx LERMIT, Faculté de Pharmacie, Université Paris-Sud, 92296 Châtenay-Malabry, France   eMail: laurent.evanno@u-psud.fr   eMail: erwan.poupon@u-psud.fr
,
Erwan Poupon*
a  Laboratoire de Pharmacognosie associé au CNRS, UMR 8076 BioCIS, LabEx LERMIT, Faculté de Pharmacie, Université Paris-Sud, 92296 Châtenay-Malabry, France   eMail: laurent.evanno@u-psud.fr   eMail: erwan.poupon@u-psud.fr
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Publikationsverlauf

Received: 13. April 2015

Accepted after revision: 11. Juni 2015

Publikationsdatum:
24. Juli 2015 (online)


Abstract

Aplysinopsin monomers are considered as plausible biosynthetic precursors of the wider aplysinopsin family of marine alkaloids. The idea of harnessing their intrinsic reactivity to undertake the synthesis of dictazoles or cycloaplysinopsins logically emerged from this status. These biosynthetic considerations led us to the first total syntheses of dictazole B and other valuable cyclobutanes. When further exploiting pre-encoded reactivity, our first total synthesis of tubastrindole B originated from the ring-expansion cascade of its dictazole-type precursor. Moreover, the isolation of a transient biosynthetic intermediate combined with dimerization outcomes of a hydantoin-containing monomer allowed us to explain the formation of cycloaplysinopsins A and B.

1 Introduction

2 Easy Access to Dictazole Cyclobutanes

3 Synthesis of Cycloaplysinopsins by Ring Expansion

4 Conclusion and Future Prospects

Supporting Information

 
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  • 15 Saturation of a solution of 11 in water is visible from less than 0.1 mg/mL (i.e., 0.2 mM).
  • 16 Experiments carried out with various proportions of water and DMSO or DMF as cosolvent from 10% to 100% of cosolvent.
  • 17 See the Supporting Information for an LC/MS chromatogram showing the formation of an isomeric compound [M + H]+ = 511.2092 from 10 in highly diluted medium.