The structure of fumitremorgin A

Present review describes research on more than 280 natural anticancer agents isolated from terrestrial and marine sources and synthetic biologically active peroxides. Intensive searches for new classes of pharmacologically potent agents produced by terrestrial and marine organisms have resulted in the discovery of dozens of compounds possessing high cytotoxic, antibacterial, antimalarial, and other activities as an important source of leads for drug discovery.

This chapter discusses the chemistry and reactions of cyclic tautomers derived from tryptamines in the broad sense. There are many naturally occurring indole alkaloids that have substituents at the benzene moiety of the indole ring. The reactivity of cyclic tautomers differs from that of the open chain isomers, the indolic forms, and the 5 and 6 positions of cyclic tautomers are reactive sites for electrophilic substitution and oxidation. Biological oxidation of tryptophan to 5-hydroxytryptophan by a monooxygenase is well known, which suggests that cyclic tautomers play an important role in the enzymatic reaction, although the detailed mechanism is not established. Rhazidine is isolated from the bark of Aspidosperma quebrancho blanco as a major alkaloid, and is an example of indolenine–pyrroloindole tautomerism. The dye-sensitized photooxygenation of tryptophan gives different products depending on the various media.

Total synthesis of the title compounds is described. The key intermediate, dehydro-pentacyclic 13, is prepared in a sequence involving Pictet-Spengler reaction and DDQ oxidation. The key step in the synthesis was the dihydroxylation of 13 to afford the $\text{cis}$-diol 54, which was performed by direct oxidation with osmium tetroxide, whereas treatment of 13 with N-bromo-succinimide provided the $\text{trans}$-diol 41. Subsequent selective prenylation of 41 and 54 gave 13-epi-fumitremorgin B (45) and fumitremorgin B (1), respectively. 13-Epi-compound 45 is also converted into fumitremorgin B (1) by oxidation followed by reduction.

The fungal alkaloids seem to be characteristic in utilizing amino acid itself as its component in contrast to the higher plant alkaloids, which are biosynthesized mainly from the amine produced by decarboxylation of amino acid. This chapter provides an overview of the fungal alkaloidal metabolites isolated from Aspergillus species, which are classified by biogenetic category. Aspergillic acid, C₁₂H₂₀N₂O₂, is a monobasic acid that also possesses a weakly basic group. A deep red coloration with FeCl₃ and formation of a green cupric salt suggests that aspergillic acid is a hydroxamic acid derivative. Aspergillic acid is produced by Asp. flavus grown on a medium supplemented with radioactive leucine and isoleucine, and hydrolysis of the labeled metabolite shows that it is biosynthesized from one molecule each of leucine and isoleucine. Few fungal metabolites consist of a diketopiperazine ring derived from tryptophan and an amino acid other than alanine and proline. Those known in Aspergillus species include ditryptophenaline and D-valyl-L-tryptophan anhydride.