New Tryptophan Metabolites from Cultures of the Lipophilic Yeast Malassezia furfur

Abstract

Eleven new indole alkaloids were isolated from cultures of the human pathogenic yeast Malassezia furfur after addition of L‐tryptophan as the sole N‐source: pityriacitrin B (2), the malassezindoles A (3) and B (4), malassezialactic acid (6), the malasseziazoles A (7), B (8), and C (9), pityriazole (10), malasseziacitrin (11), and malassezione (12), along with the known d‐indole‐3‐lactic acid (=(αR)‐α‐hydroxy‐1H‐indole‐3‐propanoic acid 5), and 2‐hydroxy‐1‐(1H‐indol‐3‐yl)ethanone (13). The structural elucidation of these compounds was performed by spectroscopic methods (MS as well as 1D‐ and 2D‐NMR). The biogenetic relationships (Scheme) and biological activities of the new metabolites are discussed.

Synthesis of Biologically Active Carbazole Alkaloids Using Selective Transition-metal-catalyzed Coupling Reactions

“…Heating the diarylamine 48 in air in the presence of catalytic amounts of palladium(II) acetate and copper(II) acetate led to a triple C-H bond activation. This palladium(II)-catalyzed process resulted in the Wacker oxidation followed by intramolecular C-C bond formation and thus, provided directly euchrestifoline (45) in two steps and 37% overall yield based on bromobenzene (46). Isolation of the Wacker product after a reaction time of 24 h, and its subsequent conversion into euchrestifoline (45) by palladium(II)-catalyzed oxidative cyclization, confirmed that activation of the vinylic C-H bond takes place first.…”

“…52 For the total synthesis of this natural product, we have designed a palladium(II)-catalyzed one-pot triple C-H bond activation as key step leading to the Wacker oxidation with concomitant intramolecular oxidative C-C bond formation (Scheme 14). The diarylamine precursor is obtained by a palladium(0)-catalyzed Buchwald-Hartwig coupling of bromobenzene (46) and aminochromene 47.…”

“…53 The Buchwald-Hartwig coupling of bromobenzene (46) and the aminochromene 47 afforded diarylamine 48 (Scheme 15). Heating the diarylamine 48 in air in the presence of catalytic amounts of palladium(II) acetate and copper(II) acetate led to a triple C-H bond activation.…”

Generation of Indole Alkaloids in the Human‐Pathogenic Fungus Exophiala dermatitidis

“…This method has already been applied successfully to stimulation of the production of indole alkaloids in M. furfur. [6] By this means, exophialin (2) has been isolated from the wild-type strain of E. dermatitidis, while 8-hydroxyexophialin (1) has been isolated from the mutant Mel-1 of E. dermatitidis which is deficient in the biosynthesis of 1,8-dihydroxynaphthalene melanin, thus enriching the aromatic polyketide flavioline (7) (Figure 1). The origin of the new alkaloids and of the known indole alkaloid pityriacitrin (3) [7] has also been investigated.…”

“…A number of indole alkaloids have been isolated from the human-pathogenic lipophilic yeast Malassezia furfur, one of the causative agents of pityriasis versicolor. [6] Several of these indole alkaloids are sus-pected of contributing to the pathogenicity of M. furfur. We decided therfore to extend the screening for indole alkaloids to E. dermatitidis including different mutants [4] deficient in the biosynthesis of 1,8-dihydroxynaphthalene melanin.…”