Discovery of gargantulides B and C, new 52-membered macrolactones from Amycolatopsis sp. Complete absolute stereochemistry of the gargantulide family

Gargantulides B and C, two new and highly complex 52-membered glycosylated macrolactones, were isolated from Amycolatopsis sp. strain CA-230715 during an antibacterial screening campaign. The structures of these giant macrolides...

Efficient Isolation and Structure Analysis of (+)-Ranuncoside, a Unique Tricyclic Spiroacetal Glycoside, from Christmas Rose (Helleborus niger L.)

The use of medicinal herbs as remedies reaches back to the Stone Age, and their importance as a source of drugs has continuously increased since then. Herbal ingredients can serve as active pharmaceuticals themselves or as lead substances for the development of synthetic pharmaceuticals with less toxicity, higher effectiveness or with new properties. To date, only 6% of the ∼600,000 plants on earth have been tested pharmacologically. Among these, the medicinal plant Helleborus niger L. (Christmas rose) is especially promising because its leaves contain ( + )-ranuncoside 1, characterized by a spiroacetal ring system, a motif which is responsible for the biological activity of a multitude of natural products. Structure-activity relationship studies of ( + )-ranuncoside 1 are lacking and no synthesis of 1 has been described yet. Therefore, we developed a protocol for the rapid and efficient isolation of 1 from the leaves of cultivated Christmas rose. Crystals of high purity were obtained that enabled us to study the stereochemistry of 1 by NMR spectroscopy in solution for the first time. The spiro configuration, the absolute stereochemistry, and the geometry of all three rings was then confirmed by x-ray structure analysis. Our data will enable future structure-activity relationship studies to assess the potential of 1 as a lead substance for the development of novel antibiotics and anticancer agents.

Total Synthesis of Decahydroquinoline Poison Frog Alkaloids ent-cis-195A and cis-211A

The total synthesis of two decahydroquinoline poison frog alkaloids ent-cis-195A and cis-211A were achieved in 16 steps (38% overall yield) and 19 steps (31% overall yield), respectively, starting from known compound 1. Both alkaloids were synthesized from the common key intermediate 11 in a divergent fashion, and the absolute stereochemistry of natural cis-211A was determined to be 2R, 4aR, 5R, 6S, and 8aS. Interestingly, the absolute configuration of the parent decahydroquinoline nuclei of cis-211A was the mirror image of that of cis-195A, although both alkaloids were isolated from the same poison frog species, Oophaga (Dendrobates) pumilio, from Panama.

Oceanalin B, a Hybrid α,ω-Bifunctionalized Sphingoid Tetrahydroisoquinoline β-Glycoside from the Marine Sponge Oceanapia sp.

Oceanalin B (1), an α,ω-bipolar natural product belonging to a rare family of sphingoid tetrahydoisoquinoline β-glycosides, was isolated from the EtOH extract of the lyophilized marine sponge Oceanapia sp. as the second member of the series after oceanalin A (2) from the same animal. The compounds are of particular interest due to their biogenetically unexpected structures as well as their biological activities. The structure and absolute stereochemistry of 1 as a α,ω-bifunctionalized sphingoid tetrahydroisoquinoline β-glycoside was elucidated using NMR, CD and MS spectral analysis and chemical degradation. Oceanalin B exhibited in vitro antifungal activity against Candidaglabrata with a MIC of 25 μg/mL.

Enzymatic transformation products of phloretin as potent anti-adipogenic compounds

Enzymatic structure modification of the representative chalcone phloretin (1) with polyphenol oxidase from Agaricus bisporus origin produced two new biphenyl-type phloreoxin (2) and phloreoxinone (3), and a previously undescribed (2R)-5,7,3“,5”-tetrahydroxyflavanone (4). The structure of these new oxidized products 2‒4 elucidated by interpreting the spectroscopic data (NMR and FABMS) containing the absolute stereochemistry established by analysis of the circular dichroism (CD) spectrum. Compared to the original phloretin, the new products (2) and (3) showed highly improved anti-adipogenic potencies both toward pancreatic lipase and accumulation of 3T3-L1 cells. Aslo, phloreoxin (2) effectively inhibited the expression of C/EBPβ, PPARγ, and aP2 at the mRNA level in the 3T3 adipocytes. Thus, phloreoxin (2), containing a biphenyl moiety catalyzed by A. bisporus polyphenol oxidase, have the potential to influence the anti-adipogenic capacity.

A New Isoflavan From the Heartwood of Dalbergia cochinchinensis

A new isoflavan, named dalbergiacochan A (1), was isolated from the heartwood of Dalbergia cochinchinensis, along with two known isoflavans, namely mucronulatol (2) and 2′-O-methylsepiol (3). Their structures were elucidated based on extensive spectroscopic analyses, including one-dimensional (1D) and two-dimensional nuclear magnetic resonance (2D NMR), and mass spectroscopy (MS) data, and the absolute stereochemistry of compound 1 was determined as R-3′,6-dihydroxy-2′,4′,8-trimethoxyisoflavan from its circular dichroism spectrum. Compound 1 was inactive against Escherichia coli, Bacillus thuringiensis, and Shigella dysenteriae.

Fusaripyridines A and B; Highly Oxygenated Antimicrobial Alkaloid Dimers Featuring an Unprecedented 1,4-Bis(2-hydroxy-1,2-dihydropyridin-2-yl)butane-2,3-dione Core from the Marine Fungus Fusarium sp. LY019

The fungal strain, Fusarium sp. LY019, was obtained from the Red Sea sponge Suberea mollis. Bioassay-directed partition of the antimicrobial fraction of the extract of the culture of the fungus provided two dimeric alkaloids, fusaripyridines A and B (1 and 2). The compounds possess a previously unreported moiety, 1,4-bis(2-hydroxy-1,2-dihydropyridin-2-yl)butane-2,3-dione. Further, the compounds display a highly oxygenated substitution pattern on the dihydropyridine moieties, representing an additional feature of the fusaripyridines. Fusaripyridines A and B are the first examples of natural products possessing 1,4-bis(2-hydroxy-1,2-dihydropyridin-2-yl)butane-2,3-dione backbone. Careful analyses of the one- and two-dimensional NMR and HRESIMS spectra of the compounds secured their structural mapping, while their absolute stereochemistry was established by analyses of their ECD spectra. The production of such dimeric alkaloids with an unprecedented moiety in the culture of Fusarium sp. LY019 supports further understanding of the biosynthetic competences of the cultured marine-derived fungi. Fusaripyridines A and B selectively inhibited the growth of Candida albicans with MIC values down to 8.0 µM, while they are moderately active against S. aureus, E. coli and HeLa cells.

Asymmetric Synthesis of 1,2-Limonene Epoxides by Jacobsen Epoxidation

This study reported an asymmetric synthesis of 1,2-limonene epoxides. The absolute stereochemistry was controlled by a Jacobsen epoxidation of cis-1,2-limonene epoxide (with diastereomeric excess of 98%) and trans-1,2-limonene epoxide (with diastereomeric excess of 94%), which could be used as important raw materials for the preparation of related cannabinoid drugs.

Novel Ansa-Chain Conformation of a Semi-Synthetic Rifamycin Prepared Employing the Alder-Ene Reaction: Crystal Structure and Absolute Stereochemistry

Rifamycins are an extremely important class of antibacterial agents whose action results from the inhibition of DNA-dependent RNA synthesis. A special arrangement of unsubstituted hydroxy groups at C21 and C23, with oxygen atoms at C1 and C8 is essential for activity. Moreover, it is known that the antibacterial action of rifamycin is lost if either of the two former hydroxy groups undergo substitution and are no longer free to act in enzyme inhibition. In the present work, we describe the successful use of an Alder-Ene reaction between Rifamycin O, 1 and diethyl azodicarboxylate, yielding 2, which was a targeted introduction of a relatively bulky group close to C21 to protect its hydroxy group. Many related azo diesters were found to react analogously, giving one predominant product in each case. To determine unambiguously the stereochemistry of the Alder-Ene addition process, a crystalline zwitterionic derivative 3 of the diethyl azodicarboxylate adduct 2 was prepared by reductive amination at its spirocyclic centre C4. The adduct, as a mono chloroform solvate, crystallized in the non-centrosymmetric Sohnke orthorhombic space group, P212121. The unique conformation and absolute stereochemistry of 3 revealed through X-ray crystal structure analysis is described.