Conformation‐Enabled Total Syntheses of Ohmyungsamycins A and B and Structural Revision of Ohmyungsamycin B

Abstract

The first total syntheses of the bioactive cyclodepsipeptides ohmyungsamycin A and B are described. Key features of our synthesis include the concise preparation of a linear cyclization precursor that consists of N-methyl amides and non-proteinogenic amino acids, and its macrolactamization from a bent conformation. The proposed structure of ohmyungsamycin B was revised based on its synthesis. The cyclic core of the ohmyungsamycins was shown to be responsible for the excellent antituberculosis activity, and ohmyungsamycin variants with truncated chains were evaluated for their biological activity.

Donghaecyclinones A–C: New Cytotoxic Rearranged Angucyclinones from a Volcanic Island-Derived Marine Streptomyces sp.

“…(Table 1) of 2 showed similar features to those of 1, indicating that donghaecyclinone B is also a polyunsaturated aromatic natural product. Analysis of the 1 H, 13 Based on its molecular formula, we determined that donghaecyclinone B bears 11 unsaturation equivalents. Two carbonyl functional groups and 12 double-bond signals comprising six double bonds correspond to seven degrees of unsaturation, indicating that donghaecyclinone B (2) is a tetracyclic compound.…”

“…ECD spectra were recorded on an Applied Photophysics Chirascan-plus circular dichroism spectrometer. 1 H, 13 C, and 2D NMR spectra were acquired on Bruker Avance 600 MHz and 850 MHz spectrometers (Bruker, Billerica, MA, USA) at the National Center for Inter-University Research Facilities (NCIRF) at Seoul National University. High-resolution fast atom bombardment (HR-FAB) mass spectra were recorded using a Jeol JMS-600W high-resolution mass spectrometer (Jeol, München, Germany) at the NCIRF.…”

“…In this regard, we have been examining the chemical profiles of actinobacterial strains that inhabit the marine environments of volcanic islands, which may provide unique microbial habitats with volcanic minerals and salts from the surrounding seawater [11]. This has led to the successful discovery of various classes of new natural products [12][13][14][15][16][17][18] from volcanic island-derived marine actinomycetes. These include new cyclic peptides with anticancer and antituberculosis activities, ohmyungsamycins A and B [12], new anti-inflammatory linear polyketides, succinilenes A-D [17], and donghaesulfins A and B, which are dimeric benz[a]anthracenes linked through a sulfide bond [18].…”

“…The 1-D and 2-D NMR spectroscopic data(Table 1) of 2 showed similar features to those of 1, indicating that donghaecyclinone B is also a polyunsaturated aromatic natural product. Analysis of the 1 H,13 C, and HSQC NMR data revealed the presence of two carbonyl carbons (δC 201.2 and 169.3), five aromatic methines (δC/δH: 136.2/7.54, 130.5/7.59, 122.0/7.03, 115.1/6.92, and 113.3/7.04), seven nonprotonated aromatic carbons (δC 158.9, 157.5, 153.9, 139.9, 133.9, 122.9, and 116.0), two oxymethines (δC/δH: 76.4/ 7.43 and 74.4/4.55), one methoxy group (δC/δH: 56.1/3.93), one aliphatic methylene (δC/δH: 46.8/2.81 and 2.64), one aliphatic methine (δC/δH: 39.6/2.29), one methyl group (δC/δH: 18.9/1.20), and two hydroxy group protons (δH 8.83 and 4.69). Detailed comparison of the NMR data with those of 1…”

Characterization of the Ohmyungsamycin Biosynthetic Pathway and Generation of Derivatives with Improved Antituberculosis Activity

“…In addition, the antiproliferative and antituberculosis activities of the OMS derivatives dehydroxy-OMS A (4) and demethoxy-OMS A (6) obtained from the mutant strains were evaluated in vitro. Interestingly, dehydroxy-OMS A (4) displayed significantly improved antituberculosis activity and decreased cytotoxicity compared to wild-type OMS A.Biomolecules 2019, 9, 672 2 of 15 respectively [3]. The OMSs are composed of 12 amino acid units, including two non-proteinogenic and four N-methylated amino acids [1,3].…”