Stephacidin

Stephacidin A and B are antitumor alkaloids isolated from the fungus Aspergillus ochraceus that belong to a class of naturally occurring 2,5-diketopiperazines. This unusual family of fungal metabolites are complex bridged 2,5-diketopiperazine alkaloids that possess a unique bicyclodiazaoctane core ring system and are constituted mainly from tryptophan, proline, and substituted proline derivatives where the olefinic unit of the isoprene moiety has been formally oxidatively cyclized across the α-carbon atoms of a 2,5-diketopiperazine ring.The molecular architecture of stephacidin B, formally a dimer of avrainvillamide, reveals a complex dimeric prenylated N-hydroxyindole alkaloid that contains 15 rings and 9 stereogenic centers and is one of the most complex indole alkaloids isolated from fungi. Stephacidin B rapidly converts into the electrophilic monomer avrainvillamide in cell culture, and there is evidence that the monomer avrainvillamide interacts with intracellular thiol-containing proteins, most likely by covalent modification. Stephacidin A and B are antitumor alkaloids isolated from the fungus Aspergillus ochraceus that belong to a class of naturally occurring 2,5-diketopiperazines. This unusual family of fungal metabolites are complex bridged 2,5-diketopiperazine alkaloids that possess a unique bicyclodiazaoctane core ring system and are constituted mainly from tryptophan, proline, and substituted proline derivatives where the olefinic unit of the isoprene moiety has been formally oxidatively cyclized across the α-carbon atoms of a 2,5-diketopiperazine ring.The molecular architecture of stephacidin B, formally a dimer of avrainvillamide, reveals a complex dimeric prenylated N-hydroxyindole alkaloid that contains 15 rings and 9 stereogenic centers and is one of the most complex indole alkaloids isolated from fungi. Stephacidin B rapidly converts into the electrophilic monomer avrainvillamide in cell culture, and there is evidence that the monomer avrainvillamide interacts with intracellular thiol-containing proteins, most likely by covalent modification. Avrainvillamide, which contains a 3-alkylidene-3H-indole 1-oxide function, was identified in culture media from various strains of Aspergillus and is reported to exhibitantimicrobial activity against multidrug-resistant bacteria.The avrainvillamide and stephacidins family of structurally complex anticancer natural products are active against the human colon HCT 116 cell line.The signature bicyclodiazaoctane ring system common to these alkaloids has inspired numerous synthetic approaches.