环状亚胺毒素的稳定性：水相中介导杯状冠螺毒素氨基酸酮和杯状冠螺毒素 A 的互变。
Stability of cyclic imine toxins: interconversion of pinnatoxin amino ketone and pinnatoxin A in aqueous media.
机构信息
Department of Chemistry and Biochemistry, University of California, Santa Barbara, California 93106-9510, USA.
出版信息
J Org Chem. 2012 Nov 16;77(22):10435-40. doi: 10.1021/jo301632d. Epub 2012 Nov 6.
Abstract
Pinnatoxins belong to the cyclic imine (CI) group of marine toxins with a unique toxicological profile. The need for structural integrity of the aliphatic 7-membered cyclic imine for the potent bioactivity of pinnatoxins has been experimentally demonstrated. In this study, we probe interconversion of the natural cyclic imine and its open form, pinnatoxin A amino ketone (PnTX AK), under physiologically relevant aqueous conditions. Our studies demonstrate the high stability of PnTX A. The unusual stability of the imine ring in PnTX A has implications for its oral toxicity and detoxification. These studies, as well the access to PnTX amino ketone, were enabled by the total synthesis of (+)-pinnatoxin A completed previously in our laboratory.
摘要
扇贝毒素属于海洋毒素中环胺（CI）组，具有独特的毒理学特征。实验证明，为了保持扇贝毒素的强烈生物活性，需要脂肪族 7 元环胺的结构完整性。在这项研究中，我们在生理相关的水性条件下探测天然环胺及其开环形式，扇贝毒素 A 氨基酮（PnTX AK）之间的互变。我们的研究表明 PnTX A 具有很高的稳定性。PnTX A 中环胺的不寻常稳定性对其口服毒性和解毒有影响。这些研究以及 PnTX 氨基酮的获得，得益于我们实验室之前完成的 (+)-扇贝毒素 A 的全合成。
相似文献
1
Stability of cyclic imine toxins: interconversion of pinnatoxin amino ketone and pinnatoxin A in aqueous media.
J Org Chem. 2012 Nov 16;77(22):10435-40. doi: 10.1021/jo301632d. Epub 2012 Nov 6.
2
Marine Macrocyclic Imines, Pinnatoxins A and G: Structural Determinants and Functional Properties to Distinguish Neuronal α7 from Muscle α1(2)βγδ nAChRs.
Structure. 2015 Jun 2;23(6):1106-15. doi: 10.1016/j.str.2015.04.009. Epub 2015 May 21.
3
Pinnatoxin G is responsible for atypical toxicity in mussels (Mytilus galloprovincialis) and clams (Venerupis decussata) from Ingril, a French Mediterranean lagoon.
Toxicon. 2013 Dec 1;75:16-26. doi: 10.1016/j.toxicon.2013.05.001. Epub 2013 May 30.
4
A formal total synthesis of (+)-pinnatoxin A.
Angew Chem Int Ed Engl. 2004 Dec 3;43(47):6505-10. doi: 10.1002/anie.200461802.
5
Acute Oral Toxicity of Pinnatoxin G in Mice.
Toxins (Basel). 2020 Jan 28;12(2):87. doi: 10.3390/toxins12020087.
6
An approach to the imine ring system of pinnatoxins.
Org Lett. 2005 Apr 14;7(8):1629-31. doi: 10.1021/ol050321l.
7
Synthetic Pinnatoxins A and G Reversibly Block Mouse Skeletal Neuromuscular Transmission In Vivo and In Vitro.
Mar Drugs. 2019 May 24;17(5):306. doi: 10.3390/md17050306.
8
A stereoselective synthesis of the C10-C31 (BCDEF ring) portion of pinnatoxin A.
Org Lett. 2001 Dec 13;3(25):4075-8. doi: 10.1021/ol0168364.
9
Total synthesis of pinnatoxins A and G and revision of the mode of action of pinnatoxin A.
J Am Chem Soc. 2011 Jul 13;133(27):10499-511. doi: 10.1021/ja201254c. Epub 2011 Jun 17.
10
Cytotoxicity, fractionation and dereplication of extracts of the dinoflagellate Vulcanodinium rugosum, a producer of pinnatoxin G.
Mar Drugs. 2013 Sep 2;11(9):3350-71. doi: 10.3390/md11093350.
引用本文的文献
1
Stability and Chemical Conversion of the Purified Reference Material of Gymnodimine-A under Different Temperature and pH Conditions.
Toxins (Basel). 2022 Oct 29;14(11):744. doi: 10.3390/toxins14110744.
2
Detection and Spatio-Temporal Distribution of Pinnatoxins in Shellfish from the Atlantic and Cantabrian Coasts of Spain.
Toxins (Basel). 2019 Jun 14;11(6):340. doi: 10.3390/toxins11060340.
3
Synthetic Pinnatoxins A and G Reversibly Block Mouse Skeletal Neuromuscular Transmission In Vivo and In Vitro.
Mar Drugs. 2019 May 24;17(5):306. doi: 10.3390/md17050306.
4
Cyclic imine toxins from dinoflagellates: a growing family of potent antagonists of the nicotinic acetylcholine receptors.
J Neurochem. 2017 Aug;142 Suppl 2(Suppl 2):41-51. doi: 10.1111/jnc.13995. Epub 2017 Mar 21.
5
Marine harmful algal blooms, human health and wellbeing: challenges and opportunities in the 21st century.
J Mar Biol Assoc U K. 2015;2015. doi: 10.1017/S0025315415001733. Epub 2015 Nov 20.
6
Marine Macrocyclic Imines, Pinnatoxins A and G: Structural Determinants and Functional Properties to Distinguish Neuronal α7 from Muscle α1(2)βγδ nAChRs.
Structure. 2015 Jun 2;23(6):1106-15. doi: 10.1016/j.str.2015.04.009. Epub 2015 May 21.
7
Synthesis and biology of cyclic imine toxins, an emerging class of potent, globally distributed marine toxins.
Nat Prod Rep. 2015 Mar;32(3):411-35. doi: 10.1039/c4np00089g.
8
Cytotoxicity, fractionation and dereplication of extracts of the dinoflagellate Vulcanodinium rugosum, a producer of pinnatoxin G.
Mar Drugs. 2013 Sep 2;11(9):3350-71. doi: 10.3390/md11093350.
9
Pinnatoxin G is responsible for atypical toxicity in mussels (Mytilus galloprovincialis) and clams (Venerupis decussata) from Ingril, a French Mediterranean lagoon.
Toxicon. 2013 Dec 1;75:16-26. doi: 10.1016/j.toxicon.2013.05.001. Epub 2013 May 30.
本文引用的文献
1
Studies toward the synthesis of spirolide C: exploration into the formation of the 23-membered all-carbon macrocyclic framework.
Org Lett. 2012 Feb 3;14(3):804-7. doi: 10.1021/ol203342e. Epub 2012 Jan 19.
2
Total synthesis of the spirocyclic imine marine toxin (-)-gymnodimine and an unnatural C4-epimer.
J Am Chem Soc. 2011 Dec 14;133(49):19844-56. doi: 10.1021/ja207385y. Epub 2011 Nov 16.
3
Effect of counterion structure on rates and diastereoselectivities in α,β-unsaturated iminium-ion Diels-Alder reactions.
Org Lett. 2011 Jul 15;13(14):3758-61. doi: 10.1021/ol201448h. Epub 2011 Jun 16.
4
Total synthesis of pinnatoxins A and G and revision of the mode of action of pinnatoxin A.
J Am Chem Soc. 2011 Jul 13;133(27):10499-511. doi: 10.1021/ja201254c. Epub 2011 Jun 17.
5
Spiroimine shellfish poisoning (SSP) and the spirolide family of shellfish toxins: isolation, structure, biological activity and synthesis.
Nat Prod Rep. 2010 Sep;27(9):1350-66. doi: 10.1039/c005400n. Epub 2010 Jun 29.
6
Isolation, structural determination and acute toxicity of pinnatoxins E, F and G.
J Agric Food Chem. 2010 May 26;58(10):6532-42. doi: 10.1021/jf100267a.
7
Structural determinants in phycotoxins and AChBP conferring high affinity binding and nicotinic AChR antagonism.
Proc Natl Acad Sci U S A. 2010 Mar 30;107(13):6076-81. doi: 10.1073/pnas.0912372107. Epub 2010 Mar 11.
8
Total synthesis of (+)-pinnatoxin A.
J Am Chem Soc. 2008 Mar 26;130(12):3774-6. doi: 10.1021/ja800435j. Epub 2008 Mar 1.
9
Acute toxicity of gymnodimine to mice.
Toxicon. 2004 Aug;44(2):173-8. doi: 10.1016/j.toxicon.2004.05.017.
10
Characterization of spirolides a, c, and 13-desmethyl c, new marine toxins isolated from toxic plankton and contaminated shellfish.
J Nat Prod. 2001 Mar;64(3):308-12. doi: 10.1021/np000416q.
Zotero 插件