Three-Component One-Pot Total Syntheses of Glyantrypine, Fumiquinazoline F, and Fiscalin B Promoted by Microwave Irradiation

Abstract

A microwave-promoted three-component one-pot reaction has been developed to provide access to the core pyrazino[2,1-b]quinazoline-3,6-dione (1) scaffold, which is common to several families of alkaloids with significant biological activities. By adapting this synthetic strategy through the use of selected Boc-amino acids and amino acid esters, we have accomplished highly efficient and concise total syntheses of glyantrypine (2), fumiquinazoline F (3), and fiscalin B (5), achieving overall yields of 55, 39, and 20%, respectively.

Cyclopeptides and polyketides from coral-associated fungus, Aspergillus versicolor LCJ-5-4

“…Its molecular formula was determined as C 31 H 37 N 5 7), and three amide protons (d H 7.50, 6.38, and 8.31), indicating its peptide nature. 1 He 1 H COSY experiment ( Fig.…”

“…4 Continuous chemical study on this fungus resulted in the isolation and identification of three new cyclopentapeptides, versicoloritides AeC (1e3), a new orcinol tetramer, tetraorcinol A (4), and two new lactones, versicolactones A and B (5 and 6), together with three known metabolites, diorcinol, 5 cordyol C, 6 and glyantrypine. 7 This paper reports the isolation, structure elucidation, and bioactivity of these new compounds.…”

Review of Microwave-Assisted Synthesis of Benzo-Fused Six-MemberedN,N-Heterocycles

“…J.-F. Liu et al [104] further explored this novel three-component one-pot strategy to generate a variety of alkaloids bearing a pyrazino [2,1-b]quinazoline-3,6-dione skeleton.…”

“…Some notable members of these families are Fumiquinazolines F and G, and Glyantrypine. [105][106][107] J.-F. Liu et al [104] applied their previously developed microwave-assisted one-pot protocol for the synthesis of Glyantrypine, Fumiquinazoline F and Fiscaline B (Scheme 37). The cleavage of the Boc protecting group was found to be strongly temperature dependent.…”

Microwave-assisted Heterocyclic Chemistry

“…The versatility of the methodology is remarkable. Simple variation of the starting materials allows not only for the decoration of the quinazolin-4-one core with diverse substituents, but also for the construction of a variety of highly complex quinazolinone-derived heterocyclic systems such as pyrazino [2,1-b]quinazolines [125], pyrrolo [2,1-b]quinazolines [126] and quinazolinobenzodiazepines [127]. Thus, a variety of pharmacologically relevant complex heterocyclic systems and biologically active natural products could be synthesized rapidly and in an automated manner.…”