Cervimycin A-D: a polyketide glycoside complex from a cave bacterium can defeat vancomycin resistance

Cervimycins A-D are novel polyketide glycosides with significant activity against multi-drug-resistant staphylococci and vancomycin-resistant enterococci. They are produced by a strain of Streptomyces tendae, isolated from an ancient cave. The structures of the cervimycins were determined by performing extensive NMR and chemical degradation studies. All cervimycins have a common tetracyclic polyketide core that is substituted with unusual di- and tetrasaccharide chains, composed exclusively of trideoxysugars; however, they differ in the acetyl and carbamoyl ring substituent and in the highly unusual terminal methylmalonyl and dimethylmalonyl residues.     

Seragakinone A, a new pentacyclic metabolite from a marine-derived fungus

A new anthracycline-derived pentacyclic metabolite, seragakinone A (1), was isolated from the mycelium of an unidentified fungus, which was separated from the Okinawan marine rhodophyta Ceralodictyon spongiosum, and the structure was elucidated by spectroscopic data.     

Cephalosol: an antimicrobial metabolite with an unprecedented skeleton from endophytic Cephalosporium acremonium IFB-E007

Cephalosol (1), a potent antimicrobial secondary metabolite with a new carbon skeleton, was characterized from the culture of Cephalosporium acremonium IFB-E007 that used to reside as an endophyte in Trachelospermum jasminoides (Apocynaceae). Its structure and absolute configuration were unambiguously determined by spectroscopic and computational approaches.     

Total synthesis of the proposed structure of the anthrapyran metabolite delta-indomycinone

The first total synthesis of the proposed structure of delta-indomycinone has been accomplished. The key steps involve the Diels-Alder reaction of a bromonaphthoquinone (6) and 1-methoxy-3-methyl-1-trimethylsiloxy-1,3-butadiene (7) to access the anthraquinone skeleton, representing a common building block of other naturally occurring anthraquinone antibiotics, regioselective bromination of anthraquinone (14) and a highly diastereoselective alkylation of enantiomerically pure dioxolanone 8. The reported synthetic approach has the advantage of high yields, excellent selectivity and a remarkable general applicability for the total synthesis of other anthrapyran natural products. The spectroscopic data obtained for the synthetic compounds 2 and 36 are not in agreement with those reported for the natural product, and therefore revision of the assigned structure is required.     

On the first polyarsenic organic compound from nature: arsenicin A from the New Caledonian marine sponge Echinochalina bargibanti

Reported here is the first polyarsenic compound ever found in nature. Denominated arsenicin A, it was isolated along a bioassay-guided fractionation of the organic extract of the poecilosclerid sponge Echinochalina bargibanti collected from the north-eastern coast of New Caledonia. In defining an adamantine-type polyarsenic structure for this compound, deceptively simple NMR spectra were complemented by extensive mass spectral analysis. However, it was only the synthesis of a model compound that provided the basis to discriminate structure 4 from other spectrally compatible structures for arsenicin A; to this end, a comparative ab initio simulation of IR spectra for the natural and the synthetic compounds was decisive. Arsenicin A is endowed with potent bactericidal and fungicidal activities on human pathogenic strains. All this may revive pharmacological interest in arsenic compounds while prompting us to rethink the arsenic cycle in nature.     

Total Synthesis,Stereochemical Reassignment,and Biological Evaluation of (−)‐Lyngbyaloside B

(?)‐Lyngbyaloside B is a 14‐membered macrolide glycoside isolated from the marine cyanobacterium Lyngbya sp. as a cytotoxic substance by Moore and co‐workers. The first total synthesis of (?)‐lyngbyaloside B and the reassignment of its stereostructure is described. The synthesis features an Abiko–Masamune aldol reaction, a vinylogous Mukaiyama aldol reaction, and a macrocyclization involving an acyl ketene intermediate for the construction of the macrocyclic backbone, which contains an acylated tertiary alcohol. The antiproliferative activity of selected compounds against a small panel of human cancer cell lines is also reported.     

Spirodionic acid, a novel metabolite from Streptomyces sp., part 1: structure elucidation and Diels-Alder-type biosynthesis

Spirodionic acid (1), a novel microbial metabolite with a spiro[4.5]decene skeleton, the 6-ethyl-2H-pyrone 5, dihydrosarkomycin (6), and other metabolites were isolated from the strain Streptomyces sp. Tü 6077. Structural elucidation was accomplished by NMR spectroscopic and mass-spectrometric studies, and the biosyntheses of compounds 1, 5, and 6 were investigated by feeding experiments with (13)C-labeled precursors. All results indicate a biogenetic sequence with metabolite 5 and sarkomycin (7) as precursors in the formation of spirocyclus 1 through an intermolecular Diels-Alder-type reaction.     

Discovery,Total Synthesis and Key Structural Elements for the Immunosuppressive Activity of Cocosolide,a Symmetrical Glycosylated Macrolide Dimer from Marine Cyanobacteria

A new dimeric macrolide xylopyranoside, cocosolide ( 1 ), was isolated from the marine cyanobacterium preliminarily identified as Symploca sp. from Guam. The structure was determined by a combination of NMR spectroscopy, HRMS, X‐ray diffraction studies and Mosher's analysis of the base hydrolysis product. Its carbon skeleton closely resembles that of clavosolides A–D isolated from the sponge Myriastra clavosa, for which no bioactivity is known. We performed the first total synthesis of cocosolide ( 1 ) along with its [α,α]‐anomer ( 26 ) and macrocyclic core ( 28 ), thus leading to the confirmation of the structure of natural 1 . The convergent synthesis featured Wadsworth–Emmons cyclopropanation, Sakurai annulation, Yamaguchi macrocyclization/dimerization reaction, α‐selective glycosidation and β‐selective glycosidation. Compounds 1 and 26 potently inhibited IL‐2 production in both T‐cell receptor dependent and independent manners. Full activity requires the presence of the sugar moiety as well as the intact dimeric structure. Cocosolide also suppressed the proliferation of anti‐CD3‐stimulated T‐cells in a dose‐dependent manner.     

Wuweizidilactones A-F: novel highly oxygenated nortriterpenoids with unusual skeletons isolated from Schisandra chinensis

A phytochemical study of secondary metabolites produced by Schisandra chinensis has led to the isolation of six novel highly oxygenated nortriterpenoids, wuweizidilactones A-F (1-6). Compounds 3-6 possess an unprecedented 3,4-seco-18(13-->14)-abeo-artane skeleton. Interestingly, structures 3-6 have a beta-oriented methyl group at the C-14 position. This structural feature corroborates the biogenetic pathway proposed for the formation of 18-norschiartane-type compounds 1 and 2. The structures of these novel metabolites were established on the basis of their detailed spectroscopic analysis. The structure of 1 was also confirmed by single-crystal X-ray diffraction analysis. For the first time, the absolute configuration of these nortriterpenoids was determined by using a modified Mosher method.     

Amycolamicin: A Novel Broad‐Spectrum Antibiotic Inhibiting Bacterial Topoisomerase

The abuse of antibacterial drugs imposes a selection pressure on bacteria that has driven the evolution of multidrug resistance in many pathogens. Our efforts to discover novel classes of antibiotics to combat these pathogens resulted in the discovery of amycolamicin (AMM). The absolute structure of AMM was determined by NMR spectroscopy, X‐ray analysis, chemical degradation, and modification of its functional groups. AMM consists of trans‐decalin, tetramic acid, two unusual sugars (amycolose and amykitanose), and dichloropyrrole carboxylic acid. The pyranose ring named as amykitanose undergoes anomerization in methanol. AMM is a potent and broad‐spectrum antibiotic against Gram‐positive pathogenic bacteria by inhibiting DNA gyrase and bacterial topoisomerase IV. The target of AMM has been proved to be the DNA gyrase B subunit and its binding mode to DNA gyrase is different from those of novobiocin and coumermycin, the known DNA gyrase inhibitors.