{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:55:57Z","timestamp":1760144157649,"version":"build-2065373602"},"reference-count":19,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2024,3,26]],"date-time":"2024-03-26T00:00:00Z","timestamp":1711411200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2018YFA0902000","81903530","NMRC-2023-3","2021-I2M-1-055"],"award-info":[{"award-number":["2018YFA0902000","81903530","NMRC-2023-3","2021-I2M-1-055"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2018YFA0902000","81903530","NMRC-2023-3","2021-I2M-1-055"],"award-info":[{"award-number":["2018YFA0902000","81903530","NMRC-2023-3","2021-I2M-1-055"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The National Microbial Resource Center","award":["2018YFA0902000","81903530","NMRC-2023-3","2021-I2M-1-055"],"award-info":[{"award-number":["2018YFA0902000","81903530","NMRC-2023-3","2021-I2M-1-055"]}]},{"name":"CAMS Innovation Fund for Medical Sciences","award":["2018YFA0902000","81903530","NMRC-2023-3","2021-I2M-1-055"],"award-info":[{"award-number":["2018YFA0902000","81903530","NMRC-2023-3","2021-I2M-1-055"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Isatropolone C from Streptomyces sp. CPCC 204095 features a fused cyclopentadienone-tropolone-oxacyclohexadiene tricyclic moiety in its structure. Herein, we report an isatropolone C dimer derivative, di-isatropolone C, formed spontaneously from isatropolone C in methanol. Notably, the structure of di-isatropolone C resolved by NMR reveals a newly formed cyclopentane ring to associate the two isatropolone C monomers. The configurations of four chiral carbons, including a ketal one, in the cyclopentane ring are assigned using quantum NMR calculations and DP4+ probability. The plausible molecular mechanism for di-isatropolone C formation is proposed, in which complex dehydrogenative C-C bond coupling may have happened to connect the two isatropolone C monomers. Like isatropolone C, di-isatropolone C shows the biological activity of inducing autophagy in HepG2 cells.<\/jats:p>","DOI":"10.3390\/molecules29071477","type":"journal-article","created":{"date-parts":[[2024,3,26]],"date-time":"2024-03-26T11:05:33Z","timestamp":1711451133000},"page":"1477","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Di-Isatropolone C, a Spontaneous Isatropolone C Dimer Derivative with Autophagy Activity"],"prefix":"10.3390","volume":"29","author":[{"given":"Jie","family":"Fu","sequence":"first","affiliation":[{"name":"CAMS Key Laboratory of Synthetic Biology for Drug Innovation, NHC Key Laboratory of Biotechnology for Microbial Drugs, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoyan","family":"Liu","sequence":"additional","affiliation":[{"name":"CAMS Key Laboratory of Synthetic Biology for Drug Innovation, NHC Key Laboratory of Biotechnology for Microbial Drugs, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miaoqing","family":"Zhang","sequence":"additional","affiliation":[{"name":"CAMS Key Laboratory of Synthetic Biology for Drug Innovation, NHC Key Laboratory of Biotechnology for Microbial Drugs, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiachang","family":"Liu","sequence":"additional","affiliation":[{"name":"CAMS Key Laboratory of Synthetic Biology for Drug Innovation, NHC Key Laboratory of Biotechnology for Microbial Drugs, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shufen","family":"Li","sequence":"additional","affiliation":[{"name":"CAMS Key Laboratory of Synthetic Biology for Drug Innovation, NHC Key Laboratory of Biotechnology for Microbial Drugs, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bingya","family":"Jiang","sequence":"additional","affiliation":[{"name":"CAMS Key Laboratory of Synthetic Biology for Drug Innovation, NHC Key Laboratory of Biotechnology for Microbial Drugs, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linzhuan","family":"Wu","sequence":"additional","affiliation":[{"name":"CAMS Key Laboratory of Synthetic Biology for Drug Innovation, NHC Key Laboratory of Biotechnology for Microbial Drugs, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4945","DOI":"10.1002\/anie.201701223","article-title":"Structure and Biosynthesis of Isatropolones, Bioactive Amine-Scavenging Fluorescent Natural Products from Streptomyces G\u00f666","volume":"56","author":"Cai","year":"2017","journal-title":"Angew. Chem. Int. Ed. Engl."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1021\/acs.jnatprod.8b00857","article-title":"Isarubrolones Containing a Pyridooxazinium Unit from Streptomyces as Autophagy Activators","volume":"82","author":"Li","year":"2019","journal-title":"J. Nat. Prod."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1038\/s41429-022-00575-x","article-title":"Isatropolone\/isarubrolone Cm from Streptomyces with Biological Activity of Inducing Incomplete Autophagy","volume":"75","author":"Li","year":"2022","journal-title":"J. Antibiot."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.1021\/acs.orglett.6b00074","article-title":"Tropolone Ring Construction in the Biosynthesis of Rubrolone B, a Cationic Tropolone Alkaloid from Endophytic Streptomyces","volume":"18","author":"Yan","year":"2016","journal-title":"Org. Lett."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Sarwar, A., Latif, Z., Zhang, S., Zhu, J., Zechel, D.L., and Bechthold, A. (2018). Biological Control of Potato Common Scab with Rare Isatropolone C Compound Produced by Plant Growth Promoting Streptomyces A1RT. Front. Microbiol., 9.","DOI":"10.3389\/fmicb.2018.01126"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"13083","DOI":"10.1038\/ncomms13083","article-title":"Non-enzymatic Pyridine Ring Formation in the Biosynthesis of the Rubrolone Tropolone Alkaloids","volume":"7","author":"Yan","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"11319","DOI":"10.1002\/chem.201802066","article-title":"Expanding the Rubterolone Family: Intrinsic Reactivity and Directed Diversification of PKS-derived Pyrans","volume":"24","author":"Guo","year":"2018","journal-title":"Chemistry"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"9338","DOI":"10.1002\/chem.201701005","article-title":"Isolation, Biosynthesis and Chemical Modifications of Rubterolones A-F: Rare Tropolone Alkaloids from Actinomadura sp. 5-2","volume":"23","author":"Guo","year":"2017","journal-title":"Chemistry"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"5541","DOI":"10.1007\/s00253-021-11404-w","article-title":"Rubrolone Production by Dactylosporangium vinaceum: Biosynthesis, Modulation and Possible Biological Function","volume":"105","author":"Moureu","year":"2021","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e202214400","DOI":"10.1002\/anie.202214400","article-title":"Actinorhodin Biosynthesis Terminates with an Unprecedented Biaryl Coupling Reaction","volume":"62","author":"Hashimoto","year":"2023","journal-title":"Angew. Chem. Int. Ed. Engl."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Zhang, C., Kong, L., Liu, Q., Lei, X., Zhu, T., Yin, J., Lin, B., Deng, Z., and You, D. (2013). In Vitro Characterization of Echinomycin Biosynthesis: Formation and Hydroxylation of L-tryptophanyl-S-enzyme and Oxidation of (2S,3S) \u03b2-Hydroxytryptophan. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0056772"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2825","DOI":"10.1021\/acs.jnatprod.7b00136","article-title":"Cytotoxic Dibohemamines D-F from a Streptomyces Species","volume":"80","author":"Jiang","year":"2017","journal-title":"J. Nat. Prod."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Liu, J., Liu, X., Fu, J., Jiang, B., Li, S., and Wu, L. (2022). Dihydroisatropolone C from Streptomyces and Its Implication in Tropolone-Ring Construction for Isatropolone Biosynthesis. Molecules, 27.","DOI":"10.3390\/molecules27092882"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2559","DOI":"10.1021\/jo00388a038","article-title":"Fast and Selective Oxidation of Primary Alcohols to Aldehydes or to Carboxylic Acids and of Secondary Alcohols to Ketones Mediated by Oxoammonium Salts under Two-phase Conditions","volume":"52","author":"Anelli","year":"1987","journal-title":"J. Org. Chem."},{"key":"ref_15","first-page":"302","article-title":"Solid State Fermentation of Streptomyces sp. CPCC 204095 and Preparation of Isatropolone C","volume":"16","author":"Liu","year":"2021","journal-title":"Chin. Med. Biotechnol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/1758-2946-3-33","article-title":"Open Babel: An Open Chemical Toolbox","volume":"3","author":"Banck","year":"2011","journal-title":"J. Cheminform."},{"key":"ref_17","unstructured":"Frisch, M.J., Trucks, G.W., Schlegel, H.B., Scuseria, G.E., Robb, M.A., Cheeseman, J.R., Scalmani, G., Barone, V., Petersson, G.A., and Nakatsuji, H. (2009). Gaussian 09, Revision E.01, Gaussian, Inc."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1839","DOI":"10.1021\/cr200106v","article-title":"Computational Prediction of 1H and 13C Chemical Shifts: A Useful Tool for Natural Product, Mechanistic, and Synthetic Organic Chemistry","volume":"112","author":"Lodewyk","year":"2012","journal-title":"Chem. Rev."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"12526","DOI":"10.1021\/acs.joc.5b02396","article-title":"Beyond DP4: An Improved Probability for the Stereochemical Assignment of Isomeric Compounds Using Quantum Chemical Calculations of NMR Shifts","volume":"80","author":"Grimblat","year":"2015","journal-title":"J. Org. Chem."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/29\/7\/1477\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:18:59Z","timestamp":1760105939000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/29\/7\/1477"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,26]]},"references-count":19,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2024,4]]}},"alternative-id":["molecules29071477"],"URL":"https:\/\/doi.org\/10.3390\/molecules29071477","relation":{},"ISSN":["1420-3049"],"issn-type":[{"type":"electronic","value":"1420-3049"}],"subject":[],"published":{"date-parts":[[2024,3,26]]}}}