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02 May 12:20

Total Synthesis of (+)-Madangamine D

by Roberto Ballette, Maria Pérez, Stefano Proto, Mercedes Amat, Joan Bosch

Abstract

Madangamines are a group of bioactive marine sponge alkaloids, embodying an unprecedented diazapentacyclic skeletal type. The enantioselective total synthesis of madangamine D has been accomplished, and represents the first total synthesis of an alkaloid of the madangamine group. It involves the stereoselective construction of the diazatricyclic ABC core using a phenylglycinol-derived lactam as the starting enantiomeric scaffold and the subsequent assembly of the peripheral macrocyclic rings. The synthesis provides, for the first time, a pure sample of madangamine D and confirms the absolute configuration of this alkaloid family.

Thumbnail image of graphical abstract

Mad about madangamines: The first total synthesis of an alkaloid of the madangamine group has been accomplished. Using a phenylglycinol-derived lactam as the starting enantiomeric scaffold, the synthesis of (+)-madangamine D involves the successive construction of the six-membered carbocyclic C and heterocyclic A rings to generate the functionalized diazatricyclic ABC intermediates and the subsequent assembly of the peripheral macrocyclic D and E rings. Ts=4-toluenesulfonyl.

26 Jul 15:41

Homopyrrole and homofuran as masked 1,5-dipoles in metal-free (5+2) cycloadditions with dienophiles: a DFT study

Publication date: 9 September 2013
Source:Tetrahedron, Volume 69, Issue 36
Author(s): Pei-Jun Cai , Fu-Qiang Shi , Yi Wang , Xin Li , Zhi-Xiang Yu
Metal-free (5+2) cycloadditions of homopyrrole and homofuran with dienophiles of N-phenylmaleimide, dimethyl acetylenedicarboxylate (DMAD), and maleic anhydride have been investigated by DFT calculations at the (U)B3LYP/6-31+G(d) level. Homopyrrole and homofuran act as 4-electron 1,5-dipoles in these (5+2) reactions. These 1,5-dipoles can exist only in the transition states and undergo competitive concerted or stepwise (5+2) cycloadditions. The (5+2) cycloadditions of homopyrrole with dienophiles are stepwise involving generation of diradical intermediates, and its concerted pathways are disfavored marginally. In contrast, the (5+2) cycloaddition of homofuran with maleic anhydride occurs in a concerted fashion, which is preferred over the stepwise diradical pathway slightly. The distortion energies from homopyrrole and homofuran to their respective 1,5-dipoles in the transition states are not high and this is the main reason why homopyrrole and homofuran can undergo metal-free (5+2) cycloadditions with dienophiles.

Graphical abstract

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