Omphalotins E–I, Five Oxidatively Modified Nematicidal Cyclopeptides from Omphalotus olearius

Abstract

Omphalotins E–I, oxidatively modified cyclic dodecapeptides, were isolated from mycelial extracts of the basidiomycete Omphalotus olearius, and their structures were determined by NMR spectroscopic and MS methods. Four of the five omphalotins contained an unprecedented N‐hydroxylated tricyclic tryptophan derivative. All compounds exhibited strong and selective nematicidal activity against the plant pathogen Meloidogyne incognita with LD90 values between 2 and 5 μg mL–1. Cytotoxic activities were not detected up to 50 μg mL–1. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

Structure, Bioactivity and Synthesis of Natural Products with Hexahydropyrrolo[2,3‐b]indole

“…[78][79][80][81][82][83][84] An extra degree of complexity is shown in kapakahines C (53) and D (54), which are macrocyclic peptides formed through a bond between the N 8 of an HPIC located at the N-terminal of the linear structure and the C 4a of an a-carboline unit, located close to the C-terminal. [85] Natural products with an HPIC integrated into the peptide chain include omphalotins B-I (D: 55), [86,87] phakellistatin 3 (56) and isophakellistatin 3; [88] himastatin (57), in which the HPIC is part of a depsipeptide-chain; [89,90] its structure and stereochemistry was revised after the total synthesis. [91,92] Other similar natural products are chloptosin (58); [93] NW-G01, an antibiotic isolated from Streptomyces alboflavus; [94] and kutznerides 1-9 (1: 59) [95,96] (Scheme 4).…”

Macrocyclic N-Methylated Cyclic Peptides and Depsipeptides

“…APCI-MS was applied for getting the molecular masses of omphalotin E-I 252-256 [225], while the elemental composition was determined by ESI-HRMS. NMR spectra run in CDCl 3 showed single conformers for omphalotin G-I 254-256 while there were minor additional conformers found for omphalotin E 252 and F 253.…”

“…[225] The NMR spectra of omphalotin G 254 indicated an additional oxygen atom compared to omphalotin F 253 that was assigned to the hydroxylation of Sar at C-53. [225] The NMR spectra of omphalotin G 254 indicated an additional oxygen atom compared to omphalotin F 253 that was assigned to the hydroxylation of Sar at C-53.…”

“…Omphalotin A 248 was reported to have nematicidal activity against Meloidogyne incognita, nematodes mostly found in olive, oak, and chestnut trees. Omphalotin B-I 249-256 were reported to possess similar nematicidal activities as omphalotin A 248 [225,226]. Omphalotin A 248 does not have phytotoxic, antibacterial, antifungal, and antimicrobial properties [223].…”

Synthesis of 3a‐hydroxyhexahydropyrrolo[2,3‐B]Indole‐2‐carboxamide, an oxidation product of tryptophan present in natural products

“…The omphalotin family comprises ten cyclo‐dodecapeptides, nine of which contain N ‐methylated amides and eight of which ( 20a ‐ h ) present an HO‐HPIC motif . The omphalotins were isolated from the basidiomycete Omphalotus olearius , and exhibited nematicidal activity (Figure ) …”