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Chemistry. 2018 Feb 9;24(9):2200-2213. doi: 10.1002/chem.201704928. Epub 2018 Jan 19.

The Rickiols: 20-, 22-, and 24-membered Macrolides from the Ascomycete Hypoxylon rickii.

Author information

1
Microbial Drugs, Helmholtz Centre for Infection Research GmbH (HZI), Inhoffenstraße 7, 38124, Braunschweig, Germany.
2
Partner site Hannover-Braunschweig, German Centre for Infection Research Association (DZIF), Inhoffenstraße 7, 38124, Braunschweig, Germany.
3
Institute for Organic Chemistry, Leibniz Universität Hannover, Schneiderberg 1B, 30167, Hannover, Germany.
4
Drug Research (BMWZ), Leibniz Universität Hannover, Schneiderberg 1B, 30167, Hannover, Germany.
5
Institut für Chemie, Technische Universität Berlin, Müller-Breslau-Straße 10, 10623, Berlin, Germany.
6
Department of Chemistry, Organic Chemistry, Cologne University, Greinstraße 4, 50939, Cologne, Germany.
7
Medicinal Chemistry, Helmholtz Centre for Infection Research GmbH (HZI), Inhoffenstraße 7, 38124, Braunschweig, Germany.

Abstract

In preceding studies the neotropical ascomycete Hypoxylon rickii turned out to be a prolific source of new secondary metabolites, considering that we had obtained terpenoids with five different scaffolds along with a series of terphenyls. From the mycelial extracts of a 70 L scale fermentation of this strain we additionally isolated nine new macrolides (1-9) by RP-HPLC. The planar structures were elucidated by NMR spectroscopy complemented by HR-ESIMS. The relative configurations were assigned by J-based configuration analyses and confirmed by Kishi's Universal Database. Subsequently, the absolute configurations were assigned by Mosher's method using the shift analysis of a tetra-MTPA derivative. For rickiol A (1) and E (5) we observed transesterification of 20-membered ring structures to 22-membered isomers rickiol A2 (6) and E2 (7), and to 24-membered isomers rickiol A3 (8) and rickiol E3 (9), respectively. Cytotoxic effects and moderate antibiotic activity against Gram-positive bacteria were observed for 1-8 and 1-6 and 8, respectively. The total synthesis of rickiol E3 (9) established easier access to these compounds.

KEYWORDS:

Kishis′s Universal Database; Mosher's method; macrolide; polyketides; total synthesis

PMID:
29168908
DOI:
10.1002/chem.201704928
[Indexed for MEDLINE]

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