{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T18:52:41Z","timestamp":1773427961891,"version":"3.50.1"},"reference-count":38,"publisher":"Wiley","issue":"31","license":[{"start":{"date-parts":[[2009,9,16]],"date-time":"2009-09-16T00:00:00Z","timestamp":1253059200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J Org Chem"],"published-print":{"date-parts":[[2009,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The novel bromotriterpene polyethers aplysqualenol A (<jats:bold>1<\/jats:bold>) and B (<jats:bold>2<\/jats:bold>) have been isolated from the Caribbean sea slug <jats:italic>Aplysia dactylomela<\/jats:italic>, collected in Puerto Rico, and their structures and relative configurational assignments established from spectroscopic data aided by quantum mechanical calculations of NMR chemical shifts. Although both these compounds may be conceived as polyoxacyclic derivatives of the C<jats:sub>30<\/jats:sub> squalene skeleton, it is notable that <jats:bold>1<\/jats:bold> and <jats:bold>2<\/jats:bold> each possess an unprecedented C15\u2010to\u2010C24 flexible chain of (14<jats:italic>S<\/jats:italic>*) spatial disposition that contains a unique ether bridge between C16 and C19. Biological activity screening tests revealed that, although aplysqualenol A (<jats:bold>1<\/jats:bold>) does not have significant antiinfective properties, it possesses potent antitumoral and antiviral activities. (\u00a9 Wiley\u2010VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2009)<\/jats:p>","DOI":"10.1002\/ejoc.200900775","type":"journal-article","created":{"date-parts":[[2009,9,16]],"date-time":"2009-09-16T14:24:50Z","timestamp":1253111090000},"page":"5327-5336","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Aplysqualenols A and B: Squalene\u2010Derived Polyethers with Antitumoral and Antiviral Activity from the Caribbean Sea Slug <i>Aplysia dactylomela<\/i>"],"prefix":"10.1002","volume":"2009","author":[{"given":"Brunilda","family":"Vera","sequence":"first","affiliation":[]},{"given":"Abimael D.","family":"Rodr\u00edguez","sequence":"additional","affiliation":[]},{"given":"Edward","family":"Avil\u00e9s","sequence":"additional","affiliation":[]},{"given":"Yasuyuki","family":"Ishikawa","sequence":"additional","affiliation":[]}],"member":"311","published-online":{"date-parts":[[2009,10,13]]},"reference":[{"key":"e_1_2_6_1_2","doi-asserted-by":"publisher","DOI":"10.1039\/b805113p"},{"key":"e_1_2_6_2_2","unstructured":"\u00a0"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1021\/np9905721"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1021\/np050240y"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tet.2005.05.051"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-971236"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1039\/a909496b"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0040-4039(01)88986-3"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0040-4039(00)94254-0"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tet.2007.07.055"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja00499a036"},{"key":"e_1_2_6_12_2","unstructured":"Squalene\u2010derived polyethers with the usual (R*) configuration at C14 (i.e. compounds5\u20138) also display H\u201014 as a doublet of doublets with two markedly different coupling constant values consistent with a chair\/twist\u2010boat B\u2013C ring system. Notwithstanding the abnormal relative stereochemistry at C14 in1is substantiated by noticeable variations in13C NMR chemical shifts about the 2 7\u2010dioxabicyclo[4.4.0]decane ring. In1 for instance C27 resonates at\u03b4= 14.8 ppm whereas all related congeners with the usual C14 (R*) configuration show this signal at\u03b4> 20 ppm. This modification in stereochemistry also causes the C11 resonance to shift downfield (i.e. from\u03b4= 76.3 ppm in7to\u03b4= 80.8 ppm in1). A reversal in relative stereochemistry at C14 also causes the nearby C28 methyl group in1to resonate at\u03b4= 18.1 ppm rather than at\u03b4= 22.9 or 23.0 ppm as seen in5and7 respectively in spite of the fact that all three compounds have the C15 (R*) configuration."},{"key":"e_1_2_6_13_2","unstructured":"The minimum\u2010energy configuration for1was identified by a Monte Carlo conformational search with the MMFF force field as implemented in the Spartan 04 software package (Wavefunction Inc. Irvine CA)."},{"key":"e_1_2_6_14_2","unstructured":"\u00a0"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1103\/PhysRev.136.B864"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1103\/PhysRev.140.A1133"},{"key":"e_1_2_6_17_2","unstructured":"We attempted to confirm the proposed structure of aplysqualenol A (1) by X\u2010ray crystallography through chemical transformation into a crystalline derivative. Thus after heating of a mixture of1and 4\u2010bromophenyl isocyanate in toluene for 3 h the desired carbamate was obtained in excellent yield but it failed to crystallize in all of the solvents tried."},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1021\/ol034853i"},{"key":"e_1_2_6_19_2","unstructured":"The procedure is based on the binding of MTPA or MPA to a resin in such a way that when attacked by the chiral molecule (i.e. compound1) the reagent part acts as an electrophile and liberates the corresponding ester derivative into the solution while the solid matrix behaves as the leaving group. The NMR spectra of the expected derivatives are then obtained without any separation workup or manipulation."},{"key":"e_1_2_6_20_2","unstructured":"The observation that acetylation at C18 and C30 of aplysqualenol B takes place readily at 25 \u00b0C points to the fact that the hydrogen bonds between the donor hydrogen atoms and the acceptor atoms in2have less than ideal geometry."},{"key":"e_1_2_6_21_2","unstructured":"Spartan 04 for Macintosh Wavefunction Inc. Irvine CA."},{"key":"e_1_2_6_22_2","unstructured":"M. J. Frisch G. W. Trucks H. B. Schlegel G. E. Scuseria M. A. Robb J. R. Cheeseman J. A. Montgomery Jr T. Vreven K. N. Kudin J. C. Burant J. M. Millam S. S. Iyengar J. Tomasi V. Barone B. Mennucci M. Cossi G. Scalmani N. Rega G. A. Petersson H. Nakatsuji M. Hada M. Ehara K. Toyota R. Fukuda J. Hasegawa M. Ishida T. Nakajima Y. Honda O. Kitao H. Nakai M. Klene X. Li J. E. Knox H. P. Hratchian J. B. Cross C. Adamo J. Jaramillo R. Gomperts R. E. Stratmann O. Yazyev A. J. Austin R. Cammi C. Pomelli J. W. Ochterski P. Y. Ayala K. Morokuma G. A. Voth P. Salvador J. J. Dannenberg V. G. Zakrzewski S. Dapprich A. D. Daniels M. C. Strain O. Farkas D. K. Malick A. D. Rabuck K. Raghavachari J. B. Foresman J. V. Ort\u00edz Q. Cui A. G. Baboul S. Clifford J. Cioslowski B. B. Stefanov G. Liu A. Liashenko P. Piskorz I. Komaromi R. L. Martin D. J. Fox T. Keith M. A. Al\u2010Laham C. Y. Peng A. Nanayakkara M. Challacombe P. M. W. Gill B. Johnson W. Chen M. W. Wong C. Gonz\u00e1lez J. A. Pople Gaussian 03 Revision C.02 Gaussian Inc. Wallingford CT 2004."},{"key":"e_1_2_6_23_2","unstructured":"\u00a0"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/mrc.1410"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1021\/cr030733c"},{"key":"e_1_2_6_26_2","unstructured":"\u00a0"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/0040-4039(82)80144-5"},{"key":"e_1_2_6_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/0031-9422(82)83189-0"},{"key":"e_1_2_6_29_2","unstructured":"Alternatively the presence of the 22\u2010OCH3group could be explained by methanolysis at the C22\u2013C23 epoxide implying that the genesis of this functionality in1and2could be artifactual."},{"key":"e_1_2_6_30_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1005484306931"},{"key":"e_1_2_6_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0040-4020(97)00028-8"},{"key":"e_1_2_6_32_2","unstructured":"Parallel configuration determination studies indicate that1 with an equatorial arrangement of the C15\u2010to\u2010C24 side chain is about 8.84 kcal\u2009mol\u20131more stable than its corresponding C14 epimer."},{"key":"e_1_2_6_33_2","unstructured":"Primary Epstein\u2013Barr virus infection in childhood is usually mild but in later life usually manifests as infectious mononucleosis."},{"key":"e_1_2_6_34_2","unstructured":"\u00a0"},{"key":"e_1_2_6_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0040-4039(01)91944-6"},{"key":"e_1_2_6_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/0040-4039(76)80067-6"},{"key":"e_1_2_6_37_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.41.5.1004"},{"key":"e_1_2_6_38_2","doi-asserted-by":"crossref","first-page":"119","DOI":"10.4269\/ajtmh.2004.70.119","volume":"70","author":"Corbett Y.","year":"2004","journal-title":"J. Trop. Med. Hyg."}],"container-title":["European Journal of Organic Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fejoc.200900775","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ejoc.200900775","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T08:16:25Z","timestamp":1760516185000},"score":1,"resource":{"primary":{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/10.1002\/ejoc.200900775"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,10,13]]},"references-count":38,"journal-issue":{"issue":"31","published-print":{"date-parts":[[2009,11]]}},"alternative-id":["10.1002\/ejoc.200900775"],"URL":"https:\/\/doi.org\/10.1002\/ejoc.200900775","archive":["Portico"],"relation":{},"ISSN":["1434-193X","1099-0690"],"issn-type":[{"value":"1434-193X","type":"print"},{"value":"1099-0690","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,10,13]]},"assertion":[{"value":"2009-07-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2009-10-13","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}