Three-component synthesis of pyran-fused biscoumarins: an entry to pyridinone- and pyranone-fused coumarins.

A base-mediated, three-component synthesis of symmetric and unsymmetric pyran-fused biscoumarins via the coupling of 4-hydroxycoumarin with 4-chloro-3-formylcoumarin in ethanol is reported. This methodology is further extended to the construction of various indole/coumarin-substituted symmetric pyran-fused biscoumarins. The unsymmetric pyran-fused biscoumarin can react with amines and 4-hydroxycoumarins under basic and acidic conditions to afford pyridinone-fused coumarins and pyranone-fused coumarins, respectively. The mechanisms of their formation are proposed.

Regiodivergent Synthesis of Bis(4-oxycoumarin)-based Dioxabicycles: Exploration of [4 + 4] (Heterocyclo)reversion/addition and 1,5-Hydrogen Shift Photochromism.

Two isomeric dioxabicyclic molecular skeletons were constructed by employing the concepts of divergent synthesis. A base-mediated and an acid-catalyzed pseudo-three-component reaction of two equivalents of 4-hydroxycoumarin and (Z)-3-chloro-3-phenylacrylaldehyde yielded the corresponding bis(4-oxycoumarin)-based 2,6- and 2,8-dioxabicycles, respectively. The prepared colorless 2,6-dioxabicycles turned red upon UV irradiation and underwent the reverse reaction when exposed to visible light. The photochromism was proposed to proceed via a sequential [4 + 4] (heterocyclo)addition/reversion and 1,5-hydrogen shift on the basis of photogenerated product-trapping experiments.

Application of Dimedone Enamines as Protecting Groups for Amines and Peptides.

A simple protocol for the protection of amines was realized through a base-catalyzed one-pot reaction of dimedone, ß-nitroalkene, and amine. Employing this strategy, a variety of amines/amino acids were protected in excellent yields. These acid/base stable protected amines can be deprotected by either ethylene diamine or hydrazine hydrate under mild conditions. The practical application of this orthogonal protecting group was demonstrated by the synthesis of cyclic peptide melanotan II via SPPS.

Base-Dependent Divergent Annulation of 4-Chloro-3-formylcoumarin and Tetrahydroisoquinoline: Application to the Synthesis of Isolamellarins and Hydroxypyrrolones.

A series of pyrrolo[2,1- a]isoquinoline and coumarin-fused pentacyclic derivatives were synthesized via base-mediated divergent annulation of 4-chloro-3-formylcoumarin and tetrahydroisoquinoline as a key step. This method was then extended to the preparation of isolamellarins A and B (isolamellarin G trimethyl ether). When exposed to UV light, the pyrrolo[2,1- a]isoquinoline- and coumarin-fused pentacycles B were found to undergo aerobic oxidation to give the corresponding hydroxypyrrolones.