Discovery of Terminal Oxazole-Bearing Natural Products by a Targeted Metabologenomic Approach.

A targeted metabologenomic method was developed to selectively discover terminal oxazole-bearing natural products from bacteria. For this, genes encoding oxazole cyclase, a key enzyme in terminal oxazole biosynthesis, were chosen as the genomic signature to screen bacterial strains that may produce oxazole-bearing compounds. Sixteen strains were identified from the screening of a bacterial DNA library (1,000 strains) using oxazole cyclase gene-targeting polymerase chain reaction (PCR) primers. The PCR amplicon sequences were subjected to phylogenetic analysis and classified into nine clades. 1H-13C coupled-HSQC NMR spectra obtained from the culture extracts of the hit strains enabled the unequivocal detection of the target compounds, including five new oxazole compounds, based on the unique 1JCH values and chemical shifts of oxazole: lenzioxazole (1) possessing an unprecedented cyclopentane, permafroxazole (2) bearing a tetraene conjugated with carboxylic acid, tenebriazine (3) incorporating two modified amino acids, and methyl-oxazolomycins A and B (4 and 5). Tenebriazine displayed inhibitory activity against pathogenic fungi, whereas methyl-oxazolomycins A and B (4 and 5) selectively showed anti-proliferative activity against estrogen receptor-positive breast cancer cells. This metabologenomic method enables the logical and efficient discovery of new microbial natural products with a target structural motif without the need for isotopic labeling.

Retinestatin, a Polyol Polyketide from a Termite Nest-Derived Streptomyces sp.

A new polyol polyketide, named retinestatin (1), was obtained and characterized from the culture of a Streptomyces strain, which was isolated from a subterranean nest of the termite Reticulitermes speratus kyushuensis Morimoto. The planar structure of 1 was elucidated on the basis of the cumulative analysis of ultraviolet, infrared, mass spectrometry, and nuclear magnetic resonance spectroscopic data. The absolute configuration of 1 at 12 chiral centers was successfully assigned by employing a J-based configuration analysis in combination with ROESY correlations, a quantum mechanics-based computational approach to calculate NMR chemical shifts, and a 3 min flash esterification by Mosher's reagents followed by NMR analysis. Biological evaluation of retinestatin (1) using an in vitro model of Parkinson's disease revealed that 1 protected SH-SY5Y dopaminergic cells from MPP+-induced cytotoxicity, indicating its neuroprotective effects.

Anithiactin D, a Phenylthiazole Natural Product from Mudflat-Derived Streptomyces sp., Suppresses Motility of Cancer Cells.

Anithiactin D (1), a 2-phenylthiazole class of natural products, was isolated from marine mudflat-derived actinomycetes Streptomyces sp. 10A085. The chemical structure of 1 was elucidated based on the interpretation of NMR and MS data. The absolute configuration of 1 was determined by comparing the experimental and calculated electronic circular dichroism (ECD) spectral data. Anithiactin D (1) significantly decreased cancer cell migration and invasion activities at a concentration of 5 µM via downregulation of the epithelial-to-mesenchymal transition (EMT) markers in A549, AGS, and Caco-2 cell lines. Moreover, 1 inhibited the activity of Rho GTPases, including Rac1 and RhoA in the A549 cell line, suppressed RhoA in AGS and Caco-2 cell lines, and decreased the mRNA expression levels of some matrix metalloproteinases (MMPs) in AGS and Caco-2 cell lines. Thus 1, which is a new entity of the 2-phenylthiazole class of natural products with a unique aniline-indole fused moiety, is a potent inhibitor of the motility of cancer cells.

Antiproliferative Activity of Piceamycin by Regulating Alpha-Actinin-4 in Gemcitabine-Resistant Pancreatic Cancer Cells.

Although gemcitabine-based regimens are widely used as an effective treatment for pancreatic cancer, acquired resistance to gemcitabine has become an increasingly common problem. Therefore, a novel therapeutic strategy to treat gemcitabine-resistant pancreatic cancer is urgently required. Piceamycin has been reported to exhibit antiproliferative activity against various cancer cells; however, its underlying molecular mechanism for anticancer activity in pancreatic cancer cells remains unexplored. Therefore, the present study evaluated the antiproliferation activity of piceamycin in a gemcitabine-resistant pancreatic cancer cell line and patient-derived pancreatic cancer organoids. Piceamycin effectively inhibited the proliferation and suppressed the expression of alpha-actinin-4, a gene that plays a pivotal role in tumorigenesis and metastasis of various cancers, in gemcitabine-resistant cells. Long-term exposure to piceamycin induced cell cycle arrest at the G0/G1 phase and caused apoptosis. Piceamycin also inhibited the invasion and migration of gemcitabine-resistant cells by modulating focal adhesion and epithelial-mesenchymal transition biomarkers. Moreover, the combination of piceamycin and gemcitabine exhibited a synergistic antiproliferative activity in gemcitabine-resistant cells. Piceamycin also effectively inhibited patient-derived pancreatic cancer organoid growth and induced apoptosis in the organoids. Taken together, these findings demonstrate that piceamycin may be an effective agent for overcoming gemcitabine resistance in pancreatic cancer.

Nonthreaded Isomers of Sungsanpin and Ulleungdin Lasso Peptides Inhibit H1299 Cancer Cell Migration.

Lasso peptides are a structurally distinct class of biologically active natural products defined by their short sequences with impressively interlocked tertiary structures. Their characteristic peptide [1]rotaxane motif confers marked proteolytic and thermal resiliency, and reports on their diverse biological functions have been credited to their exceptional sequence variability. Because of these unique properties, taken together with improved technologies for their biosynthetic production, lasso peptides are emerging as a designable scaffold for peptide-based therapeutic discovery and development. Although the defined structure of lasso peptides is recognized for its remarkable properties, the role of the motif in imparting bioactivity is less understood. For example, sungsanpin and ulleungdin are natural lasso peptides that similarly exhibit encouraging cell migration inhibitory activities in A549 lung carcinoma epithelial cells, despite sharing only one-third of the sequence homology. We hypothesized that the shape of the lasso motif is beneficial for the preorganization of the conserved residues, which might be partially retained in variants lacking the threaded structure. Herein, we describe solid-phase peptide synthesis strategies to prepare acyclic, head-to-side chain (branched), and head-to-tail (macrocyclic) cyclic variants based on the sungsanpin (Sun) and ulleungdin (Uln) sequences. Proliferation assays and time-lapse cell motility imaging studies were used to evaluate the cell inhibitory properties of natural Sun compared with the synthetic Sun and Uln isomers. These studies demonstrate that the lasso motif is not a required feature to slow cancer cell migration and more generally show that these nonthreaded isomers can retain similar activity to the natural lasso peptide despite the differences in their overall structures.

Discovery and structure elucidation of glycosyl and 5-hydroxy migrastatins from dung beetle gut Kitasatospora sp.

Two new macrocyclic secondary metabolites, glycosyl-migrastatin (1) and 5-hydroxy-migrastatin (2), were isolated from a gut bacterium Kitasatospora sp. JL24 in dung beetle Onthophagus lenzii. Based on a comprehensive analysis of the nuclear magnetic resonance (NMR), MS, and UV spectroscopic data, the planar structures of 1 and 2 were successfully identified as new derivatives of migrastatin. Compound 1 was the first glycosylated member of the migrastatin family. The absolute configuration of the sugar moiety was determined to be d-glucose through the analysis of coupling constants and ROESY correlations, followed by chemical derivatization and chromatographic comparison with authentic d- and l-glucose. Compound 2, identified as 5-hydroxy-migrastatin possessing an additional hydroxy group with a previously unreported chiral center, was assigned using Mosher's method through 19F NMR chemical shifts and confirmed with the modified Mosher's method. Genomic analysis of Kitasatospora sp. strain JL24 revealed a putative biosynthetic pathway involving an acyltransferase-less type I polyketide synthase biosynthetic gene cluster. ONE-SENTENCE SUMMARY: Two secondary metabolites, glycosyl-migrastatin (1) and 5-hydroxy-migrastatin (2), were discovered from the gut bacterium Kitasatospora sp. JL24 in the dung beetle Onthophagus lenzii.

Exploring the Diverse Landscape of Biaryl-Containing Peptides Generated by Cytochrome P450 Macrocyclases.

Cytochrome P450 enzymes (P450s) catalyze diverse oxidative cross-coupling reactions between aromatic substrates in the natural product biosynthesis. Specifically, P450s install distinct biaryl macrocyclic linkages in three families of ribosomally synthesized and post-translationally modified peptides (RiPPs). However, the chemical diversity of biaryl-containing macrocyclic RiPPs remains largely unexplored. Here, we demonstrate that P450s have the capability to generate diverse biaryl linkages on RiPPs, collectively named "cyptides". Homology-based genome mining for P450 macrocyclases revealed 19 novel groups of homologous biosynthetic gene clusters (BGCs) with distinct aromatic residue patterns in the precursor peptides. Using the P450-modified precursor peptides heterologously coexpressed with corresponding P450s in Escherichia coli, we determined the NMR structures of three novel biaryl-containing peptides─the enzymatic products, roseovertin (1), rubrin (2), and lapparbin (3)─and confirmed the formation of three unprecedented or rare biaryl linkages: Trp C-7'-to-His N-τ in 1, Trp C-7'-to-Tyr C-6 in 2, and Tyr C-6-to-Trp N-1' in 3. Biochemical characterization indicated that certain P450s in these pathways have a relaxed substrate specificity. Overall, our studies suggest that P450 macrocyclases have evolved to create diverse biaryl linkages in RiPPs, promoting the exploration of a broader chemical space for biaryl-containing peptides encoded in bacterial genomes.

Actinoquinazolinone, a New Quinazolinone Derivative from a Marine Bacterium Streptomyces sp. CNQ-617, Suppresses the Motility of Gastric Cancer Cells.

A HPLC-UV guided fractionation of the culture broth of Streptomyces sp. CNQ-617 has led to the isolation of a new quinazolinone derivative, actinoquinazolinone (1), as well as two known compounds, 7-hydroxy-6-methoxy-3,4-dihydroquinazolin-4-one (2) and 7-methoxy-8-hydroxy cycloanthranilylproline (3). The interpretation of 1D, 2D NMR, and MS spectroscopic data revealed the planar structure of 1. Furthermore, compound 1 suppressed invasion ability by inhibiting epithelial-mesenchymal transition markers (EMT) in AGS cells at a concentration of 5 µM. In addition, compound 1 decreased the expression of seventeen genes related to human cell motility and slightly suppressed the signal transducer and activator of the transcription 3 (STAT3) signal pathway in AGS cells. Together, these results demonstrate that 1 is a potent inhibitor of gastric cancer cells.

Tandocyclinones A and B, Ether Bridged C-Glycosyl Benz[a]anthracenes from an Intertidal Zone Streptomyces sp.

Two new proton-deficient metabolites, tandocyclinones A and B (1 and 2), were discovered via the chemical profiling of the Streptomyces sp. strain TDH03, which was isolated from a marine sediment sample collected from the intertidal mudflat in Tando Port, the Republic of Korea. The structures of 1 and 2 were elucidated as new ether-bridged C-glycosyl benz[a]anthracenes by using a combination of spectroscopic analyses of ultraviolet (UV) and mass spectrometry (MS) data, along with nuclear magnetic resonance (NMR) spectra, which were acquired in tetrahydrofuran (THF)-d8 selected after an extensive search for a solvent, resulting in mostly observable exchangeable protons in the 1H NMR spectrum. Their configurations were successfully assigned by applying a J-based configuration analysis, rotating-frame Overhauser enhancement spectroscopy (ROESY) NMR correlations, chemical derivatization methods based on NMR (a modified version of Mosher's method) and circular dichroism (CD) (Snatzke's method using Mo2(OAc)4-induced CD), as well as quantum-mechanics-based computational methods, to calculate the electronic circular dichroism (ECD). Tandocyclinones A and B (1 and 2) were found to have weak antifungal activity against Trichophyton mentagrophytes IFM40996 with an MIC value of 128 µg/mL (244 and 265 µM for 1 and 2, respectively). A further biological evaluation revealed that tandocyclinone A (1) displayed inhibitory activity against Mycobacterium avium (MIC50 = 40.8 µM) and antiproliferative activity against SNU638 and HCT116 cancer cells, with IC50 values of 31.9 µM and 49.4 µM, respectively.

Targeted and Logical Discovery of Piperazic Acid-Bearing Natural Products Based on Genomic and Spectroscopic Signatures.

A targeted and logical discovery method was devised for natural products containing piperazic acid (Piz), which is biosynthesized from ornithine by l-ornithine N-hydroxylase (KtzI) and N-N bond formation enzyme (KtzT). Genomic signature-based screening of a bacterial DNA library (2020 strains) using polymerase chain reaction (PCR) primers targeting ktzT identified 62 strains (3.1%). The PCR amplicons of KtzT-encoding genes were phylogenetically analyzed to classify the 23 clades into two monophyletic groups, I and II. Cultivating hit strains in media supplemented with 15NH4Cl and applying 1H-15N heteronuclear multiple bond correlation (HMBC) along with 1H-15N heteronuclear single quantum coherence (HSQC) and 1H-15N HSQC-total correlation spectroscopy (HSQC-TOCSY) NMR experiments detected the spectroscopic signatures of Piz and modified Piz. Chemical investigation of the hit strains prioritized by genomic and spectroscopic signatures led to the identification of a new azinothricin congener, polyoxyperuin B seco acid (1), previously reported chloptosin (2) in group I, depsidomycin D (3) incorporating two dehydropiperazic acids (Dpz), and lenziamides A and B (4 and 5), structurally novel 31-membered cyclic decapeptides in group II. By consolidating the phylogenetic and chemical analyses, clade-structure relationships were elucidated for 19 of the 23 clades. Lenziamide A (4) inhibited STAT3 activation and induced G2/M cell cycle arrest, apoptotic cell death, and tumor growth suppression in human colorectal cancer cells. Moreover, lenziamide A (4) resensitized 5-fluorouracil (5-FU) activity in both in vitro cell cultures and the in vivo 5-FU-resistant tumor xenograft mouse model. This work demonstrates that the genomic and spectroscopic signature-based searches provide an efficient and general strategy for new bioactive natural products containing specific structural motifs.

Jejucarbosides B-E, Chlorinated Cycloaromatized Enediynes, from a Marine Streptomyces sp.

Four new chlorinated cycloaromatized enediyne compounds, jejucarbosides B-E (1-4), were discovered together with previously-identified jejucarboside A from a marine actinomycete strain. Compounds 1-4 were identified as new chlorinated cyclopenta[a]indene glycosides based on 1D and 2D nuclear magnetic resonance, high-resolution mass spectrometry, and circular dichroism (CD) spectra. Jejucarbosides B and E bear a carbonate functional group whereas jejucarbosides C and D are variants possessing 1,2-diol by losing the carbonate functionality. It is proposed that the production of 1-4 occurs via Bergman cycloaromatization capturing Cl- and H+ in the alternative positions of a p-benzyne intermediate derived from a 9-membered enediyne core. Jejucarboside E (4) displayed significant cytotoxicity against human cancer cell lines including SNU-638, SK-HEP-1, A549, HCT116, and MDA-MB-231, with IC50 values of 0.31, 0.40, 0.25, 0.29, and 0.48 µM, respectively, while jejucarbosides B-D (1-3) showed moderate or no cytotoxic effects.

Iron-Catalyzed Oxidative Cyclization of 2-Amino Styrenes with Alcohols and Methyl Arenes for the Synthesis of Polysubstituted Quinolines.

Herein, we present the iron-catalyzed oxidative cyclization of alcohol/methyl arene with 2-amino styrene to synthesize polysubstituted quinoline. Low-oxidation level substrates such as alcohols and methyl arenes are converted to aldehydes in the presence of an iron catalyst and di-t-butyl peroxide. Then, the quinoline scaffold is synthesized through imine condensation/radical cyclization/oxidative aromatization. Our protocol showed a broad substrate scope, and various functionalization and fluorescence applications of quinoline products demonstrated its synthetic ability.

Discovery and Biosynthesis of Cihunamides, Macrocyclic Antibacterial RiPPs with a Unique C-N Linkage Formed by CYP450 Catalysis.

Cihunamides A-D (1-4), novel antibacterial RiPPs, were isolated from volcanic-island-derived Streptomyces sp. The structures of 1-4 were elucidated by 1 H, 13 C, and 15 N NMR, MS, and chemical derivatization; they contain a tetrapeptide core composed of WNIW, cyclized by a unique C-N linkage between two Trp units. Genome mining of the producer strain revealed two biosynthetic genes encoding a cytochrome P450 enzyme and a precursor peptide. Heterologous co-expression of the core genes demonstrated the biosynthesis of cihunamides through P450-mediated oxidative Trp-Trp cross-linking. Further bioinformatic analysis uncovered 252 homologous gene clusters, including that of tryptorubins, which possess a distinct Trp-Trp linkage. Cihunamides do not display the non-canonical atropisomerism shown in tryptorubins, which are the founding members of the "atropitide" family. Therefore, we propose to use a new RiPP family name, "bitryptides", for cihunamides, tryptorubins, and their congeners, wherein the Trp-Trp linkages define the structural class rather than non-canonical atropisomerism.

Chromatographic Determination of the Absolute Configuration in Sanjoinine A That Increases Nitric Oxide Production.

A chiral derivatization strategy with phenylglycine methyl ester (PGME) was employed to develop a straightforward method to determine the absolute configurations of N,N-dimethyl amino acids. The PGME derivatives were analyzed using liquid chromatography-mass spectrometry to identify the absolute configurations of various N,N-dimethyl amino acids based on their elution time and order. The established method was applied to assign the absolute configuration of the N,N-dimethyl phenylalanine in sanjoinine A (4), a cyclopeptide alkaloid isolated from Zizyphi Spinosi Semen widely used as herbal medicine for insomnia. Sanjoinine A displayed production of nitric oxide (NO) in LPS-activated RAW 264.7 cells.

Antimetastatic Activity of Apoptolidin A by Upregulation of N-Myc Downstream-Regulated Gene 1 Expression in Human Colorectal Cancer Cells.

Colorectal cancer (CRC) is one of the most prevalent tumors with high metastatic potential; consequently, finding new drug candidates that suppress tumor metastasis is essential. Apoptolidin A is a macrocyclic lactone produced by Amycolatopsis sp. DW02G. It exhibits significant cytotoxicity against several cancer cell lines, but its effects on CRC cells remain unknown. Therefore, the present study investigated the antiproliferative and antimetastatic activities of apoptolidin A and its underlying molecular mechanisms in CRC cells. Apoptolidin A effectively inhibited CRC cell growth and colony formation. The induction of G0/G1 phase cell cycle arrest was associated with the downregulation of cyclin D1 and CDK4/6 expression. Long-term exposure to apoptolidin A also induced apoptosis as confirmed by the downregulation and upregulation of Bcl-2 and Bax expression, respectively. Moreover, apoptolidin A effectively upregulated the suppressed expression of N-Myc downstream-regulated gene 1 (NDRG1), a tumor suppressor gene, in a concentration-dependent manner in CRC cells. The antimetastatic potential of apoptolidin A was also correlated with the expression of epithelial-mesenchymal transition (EMT) biomarkers, including the upregulation of E-cadherin and downregulation of N-cadherin, vimentin, snail, and MMP9 in CRC cells. These findings suggest that apoptolidin A exerts antiproliferative and antimetastatic activities by regulating the NDRG1-activated EMT pathway in CRC cells.

Sadopeptins A and B, Sulfoxide- and Piperidone-Containing Cyclic Heptapeptides with Proteasome Inhibitory Activity from a Streptomyces sp.

New sulfur-bearing natural products, sadopeptins A and B (1 and 2), were discovered from Streptomyces sp. YNK18 based on a targeted search using the characteristic isotopic signature of sulfur in mass spectrometry analysis. Compounds 1 and 2 were determined to be new cyclic heptapeptides, bearing methionine sulfoxide [Met(O)] and 3-amino-6-hydroxy-2-piperidone (Ahp), based on 1D and 2D NMR spectroscopy along with IR, UV, and MS. The configurations of sadopeptins A and B (1 and 2) were established via the analysis of the ROESY NMR correlation, oxidation, Marfey's method, and circular dichroism (CD) spectroscopy. The bioinformatics analysis of the full Streptomyces sp. YNK18 genome identified a nonribosomal peptide synthetase (NRPS) biosynthetic gene cluster (BGC), and a putative biosynthetic pathway is proposed. Sadopeptins A and B displayed proteasome-inhibitory activity without affecting cellular autophagic flux.

Marinobazzanan, a Bazzanane-Type Sesquiterpenoid, Suppresses the Cell Motility and Tumorigenesis in Cancer Cells.

Marinobazzanan (1), a new bazzanane-type sesquiterpenoid, was isolated from a marine-derived fungus belonging to the genus Acremonium. The chemical structure of 1 was elucidated using NMR and mass spectroscopic data, while the relative configurations were established through the analysis of NOESY data. The absolute configurations of 1 were determined by the modified Mosher's method as well as vibrational circular dichroism (VCD) spectra calculation and it was determined as 6R, 7R, 9R, and 10R. It was found that compound 1 was not cytotoxic to human cancer cells, including A549 (lung cancer), AGS (gastric cancer), and Caco-2 (colorectal cancer) below the concentration of 25 µM. However, compound 1 was shown to significantly decrease cancer-cell migration and invasion and soft-agar colony-formation ability at concentrations ranging from 1 to 5 µM by downregulating the expression level of KITENIN and upregulating the expression level of KAI1. Compound 1 suppressed ß-catenin-mediated TOPFLASH activity and its downstream targets in AGS, A549, and Caco-2 and slightly suppressed the Notch signal pathway in three cancer cells. Furthermore, 1 also reduced the number of metastatic nodules in an intraperitoneal xenograft mouse model.

Glycosylated and Succinylated Macrocyclic Lactones with Amyloid-ß-Aggregation-Regulating Activity from a Marine Bacillus sp.

Two new glycosylated and succinylated macrocyclic lactones, succinyl glyco-oxydifficidin (1) and succinyl macrolactin O (2), were isolated from a Bacillus strain collected from an intertidal mudflat on Anmyeon Island in Korea. The planar structures of 1 and 2 were proposed using mass spectrometric analysis and NMR spectroscopic data. The absolute configurations of 1 and 2 were determined by optical rotation, J-based configuration analysis, chemical derivatizations, including the modified Mosher's method, and quantum-mechanics-based calculation. Biological evaluation of 1 and 2 revealed that succinyl glyco-oxydifficidin (1) inhibited/dissociated amyloid ß (Aß) aggregation, whereas succinyl macrolactin O (2) inhibited Aß aggregation, indicating their therapeutic potential for disassembling and removing Aß aggregation.

Genomic and Spectroscopic Signature-Based Discovery of Natural Macrolactams.

The logical and effective discovery of macrolactams, structurally unique natural molecules with diverse biological activities, has been limited by a lack of targeted search methods. Herein, a targeted discovery method for natural macrolactams was devised by coupling genomic signature-based PCR screening of a bacterial DNA library with spectroscopic signature-based early identification of macrolactams. DNA library screening facilitated the efficient selection of 43 potential macrolactam-producing strains (3.6% of 1,188 strains screened). The PCR amplicons of the amine-deprotecting enzyme-coding genes were analyzed to predict the macrolactam type (α-methyl, α-alkyl, or ß-methyl) produced by the hit strains. 1H-15N HSQC-TOCSY NMR analysis of 15N-labeled culture extracts enabled macrolactam detection and structural type assignment without any purification steps. This method identified a high-titer Micromonospora strain producing salinilactam (1), a previously reported α-methyl macrolactam, and two Streptomyces strains producing new α-alkyl and ß-methyl macrolactams. Subsequent purification and spectroscopic analysis led to the structural revision of 1 and the discovery of muanlactam (2), an α-alkyl macrolactam with diene amide and tetraene chromophores, and concolactam (3), a ß-methyl macrolactam with a [16,6,6]-tricyclic skeleton. Detailed genomic analysis of the strains producing 1-3 identified putative biosynthetic gene clusters and pathways. Compound 2 displayed significant cytotoxicity against various cancer cell lines (IC50 = 1.58 µM against HCT116), whereas 3 showed inhibitory activity against Staphylococcus aureus sortase A. This genomic and spectroscopic signature-based method provides an efficient search strategy for new natural macrolactams and will be generally applicable for the discovery of nitrogen-bearing natural products.

Lodopyridones D - G from a marine-derived bacterium Saccharomonospora sp.

The intensive investigation of chemical components from the culture broth of the bacterium Saccharomonospora sp. CNQ-490 has yielded four new natural products, lodopyridones D - G (1 - 4) along with the previously reported compounds, lodopyridones A - C (5 - 7) and cotteslosin A (8). The planar structures of the lodopyridones D - G (1 - 4) were elucidated by interpreting the mass spectrometry, ultraviolet (UV) spectroscopy, and 1D and 2D nuclear magnetic spectroscopy (NMR) data, as well as comparing NMR data with those of the lodopyridones A - C (5 - 7).