Flavichalasines A–M, cytochalasan alkaloids from Aspergillus flavipes

Abstract

Two new tetracyclic cytochalasans, flavichalasines A and B (1 and 2), three new pentacyclic cytochalasans, flavichalasines C–E (3–5), and eight new tricyclic cytochalasans, flavichalasines F–M (6–13), together with eight known analogues (14–21), were isolated from the solid culture of Aspergillus flavipes. Structures of these new compounds were elucidated on the basis of extensive spectroscopic analyses including 1D, 2D NMR and HRESIMS data. Their absolute configurations were determined by comparison of their experimental ECD with either computed ECD or experimental ECD spectrum of known compound. The structure and absolute configuration of 2 were further determined by X-ray crystallographic diffraction. Flavichalasine A (1) represents the first example of cytochalasan with a terminal double bond at the macrocyclic ring and flavichalasine E (5) is the only cytochalasan with an α-oriented oxygen-bridge in D ring. These new compounds were evaluated for their cytotoxic activities against seven human cancer cell lines, of which, 6 and 14 displayed moderate inhibitory activities against tested cell lines. In addition, compounds 6 and 14 induced apoptosis of HL60 cells by activation of caspase-3 and degradation of PARP.

Bioinspired Network Analysis Enabled Divergent Syntheses and Structure Revision of Pentacyclic Cytochalasans

“…HCl were used as promoter, this cyclization turned much slower and both flavichalasine A ( 8 ) and flavichalasine D ( 14 ) were obtained in 75 % yield with the ratio of 1:3. The spectra and physical properties of flavichalasines A ( 8 ) and D ( 14 ) were identical to those reported for their naturally occurring counterparts [15] …”

Pycnidiophorones A–D, four new cytochalasans from the wetland derived fungus Pycnidiophora dispersa

“…Until now, only nine cytochalasan alkaloids with 5/6/6/5/6 pentacyclic system (aspergilin PZ, trichoderones A and B, trichalasin H, avichalasines C-E, spicochalasin A and xylastriasan A) have been reported previously. 16,[23][24][25][26][27] Compounds 1-10 showed moderate cytotoxicity against a panel of ve human tumor cell lines. To our knowledge, this is the rst report that cytochalasans and depsidones were isolated and identied from the genus Pycnidiophora.…”

Biomimetic Synthesis of (+)‐Aspergillin PZ

“…Aspergillin PZ ( 5 ) was first isolated in 2002 from Aspergillus awamori following a screen for antitumor and antifungal leads, and has since been re‐isolated from several species of Aspergillus as well as from Trichoderma gamsii –. Its intricate pentacyclic skeleton features one quaternary carbon and ten contiguous stereocenters, five of which reside on an oxabicyclo[3.2.1]octane subunit.…”

“…Together with the conformational restriction enforced by the 11‐membered ring, this methyl substitution plays an important role in broadening the skeletal diversity available to this cytochalasan subclass. For example, the polycyclic structures of spicochalasin A ( 4 ), aspergillin PZ ( 5 ), and flavichalasine C ( 6 ) suggest their origin from 1 , 2 , and 3 , respectively, via the intermediacy of a carbenium ion at C14. This complexity has recently been further heightened by the discovery of the heterodimeric, trimeric, and tetrameric structures of the merocytochalasans (e.g., 7 – 9 ) –.…”