天然乙酰胆碱酯酶抑制剂环磷菌素的膦酸酯类似物的合成及生物学评价
Synthesis and biological evaluation of a phosphonate analog of the natural acetyl cholinesterase inhibitor cyclophostin.
作者信息
Bandyopadhyay Saibal, Dutta Supratik, Spilling Christopher D, Dupureur Cynthia M, Rath Nigam P
机构信息
Department of Chemistry and Biochemistry, University of Missouri-St. Louis, 1 University Boulevard, St. Louis, Missouri 63121, USA.
出版信息
J Org Chem. 2008 Nov 7;73(21):8386-91. doi: 10.1021/jo801453v. Epub 2008 Sep 27.
Abstract
Two diastereomers of a phosphonate analog 6 of the AChE inhibitor cyclophostin were synthesized. The substitution reaction of phosphono allylic carbonate 10a with methyl acetoacetate gave the vinyl phosphonate 9a. Attempted hydrogenation/debenzylation gave an unexpected enolether lactone. Alternatively, selective hydrogenation, demethylation, cyclization and debenzylation gave the phosphonate analog of cyclophostin as a separable mixture of diastereomers 6. The trans phosphonate isomer was more active than the cis isomer against AChE from two sources.
摘要
合成了乙酰胆碱酯酶抑制剂环磷菌素的膦酸酯类似物6的两种非对映异构体。膦酰基烯丙基碳酸酯10a与乙酰乙酸甲酯的取代反应生成乙烯基膦酸酯9a。尝试进行氢化/脱苄反应得到了意想不到的烯醚内酯。另外，通过选择性氢化、脱甲基、环化和脱苄反应，得到了环磷菌素的膦酸酯类似物，为非对映异构体6的可分离混合物。反式膦酸酯异构体对来自两个来源的乙酰胆碱酯酶的活性比顺式异构体更高。
相似文献
1
Synthesis and biological evaluation of a phosphonate analog of the natural acetyl cholinesterase inhibitor cyclophostin.
J Org Chem. 2008 Nov 7;73(21):8386-91. doi: 10.1021/jo801453v. Epub 2008 Sep 27.
2
Synthesis and comparison of the biological activity of monocyclic phosphonate, difluorophosphonate and phosphate analogs of the natural AChE inhibitor cyclophostin.
Bioorg Med Chem. 2015 Dec 15;23(24):7529-34. doi: 10.1016/j.bmc.2015.10.044. Epub 2015 Oct 30.
3
Synthesis and kinetic analysis of some phosphonate analogs of cyclophostin as inhibitors of human acetylcholinesterase.
Bioorg Med Chem. 2010 Mar 15;18(6):2265-2274. doi: 10.1016/j.bmc.2010.01.063. Epub 2010 Feb 4.
4
Synthesis and kinetic evaluation of cyclophostin and cyclipostins phosphonate analogs as selective and potent inhibitors of microbial lipases.
J Med Chem. 2012 Nov 26;55(22):10204-19. doi: 10.1021/jm301216x. Epub 2012 Nov 7.
5
The first total synthesis of (±)-cyclophostin and (±)-cyclipostin P: inhibitors of the serine hydrolases acetyl cholinesterase and hormone sensitive lipase.
Org Lett. 2011 Jun 17;13(12):3094-7. doi: 10.1021/ol200991x. Epub 2011 May 17.
6
Rat hormone sensitive lipase inhibition by cyclipostins and their analogs.
Bioorg Med Chem. 2015 Mar 1;23(5):944-52. doi: 10.1016/j.bmc.2015.01.028. Epub 2015 Jan 22.
7
Structure-activity relationships of the phosphonate antibiotic dehydrophos.
Chem Commun (Camb). 2010 Nov 7;46(41):7694-6. doi: 10.1039/c0cc02958k. Epub 2010 Sep 27.
8
Cyclic (1R,3R)-1,3-dimethyltrimethylene [(5R)-2-hydroxy-5-methyl-5-(2- methyl-1,3-dioxolan-2-yl)-1-cyclohexen-1-yl]-phosphonate, a stable enol.
Acta Crystallogr C. 1995 Mar 15;51 ( Pt 3):479-82. doi: 10.1107/s0108270194010164.
9
Kinetic assessment of N-methyl-2-methoxypyridinium species as phosphonate anion methylating agents.
Org Lett. 2013 Mar 1;15(5):1084-7. doi: 10.1021/ol400054m. Epub 2013 Feb 14.
10
Stereoselective synthesis of cyclic ethers via the palladium-catalyzed intramolecular addition of alcohols to phosphono allylic carbonates.
Org Lett. 2009 Jul 16;11(14):3124-7. doi: 10.1021/ol900980s.
引用本文的文献
1
The Chemistry and Biology of Cyclophostin, the Cyclipostins and Related Compounds.
Molecules. 2019 Jul 16;24(14):2579. doi: 10.3390/molecules24142579.
2
Cyclipostins and Cyclophostin analogs as promising compounds in the fight against tuberculosis.
Sci Rep. 2017 Sep 18;7(1):11751. doi: 10.1038/s41598-017-11843-4.
3
Acetylcholinesterase enzyme inhibitor activity of some novel pyrazinamide condensed 1,2,3,4-tetrahydropyrimidines.
Biotechnol Rep (Amst). 2014 Oct 29;5:1-6. doi: 10.1016/j.btre.2014.10.007. eCollection 2015 Mar.
4
Rat hormone sensitive lipase inhibition by cyclipostins and their analogs.
Bioorg Med Chem. 2015 Mar 1;23(5):944-52. doi: 10.1016/j.bmc.2015.01.028. Epub 2015 Jan 22.
5
Relay cross metathesis reactions of vinylphosphonates.
Beilstein J Org Chem. 2014 Aug 19;10:1933-41. doi: 10.3762/bjoc.10.201. eCollection 2014.
6
Synthesis and kinetic evaluation of cyclophostin and cyclipostins phosphonate analogs as selective and potent inhibitors of microbial lipases.
J Med Chem. 2012 Nov 26;55(22):10204-19. doi: 10.1021/jm301216x. Epub 2012 Nov 7.
7
The first total synthesis of (±)-cyclophostin and (±)-cyclipostin P: inhibitors of the serine hydrolases acetyl cholinesterase and hormone sensitive lipase.
Org Lett. 2011 Jun 17;13(12):3094-7. doi: 10.1021/ol200991x. Epub 2011 May 17.
8
Synthesis and kinetic analysis of some phosphonate analogs of cyclophostin as inhibitors of human acetylcholinesterase.
Bioorg Med Chem. 2010 Mar 15;18(6):2265-2274. doi: 10.1016/j.bmc.2010.01.063. Epub 2010 Feb 4.
本文引用的文献
1
East meets West in the search for Alzheimer's therapeutics - novel dimeric inhibitors from tacrine and huperzine A.
Curr Alzheimer Res. 2007 Sep;4(4):386-96. doi: 10.2174/156720507781788918.
2
An in vitro comparative study on the reactivation of nerve agent-inhibited guinea pig and human acetylcholinesterases by oximes.
Biochemistry. 2007 Oct 23;46(42):11771-9. doi: 10.1021/bi701002f. Epub 2007 Sep 27.
3
Therapeutic options in autoimmune myasthenia gravis.
Autoimmun Rev. 2007 Jun;6(6):373-8. doi: 10.1016/j.autrev.2007.01.001. Epub 2007 Jan 30.
4
Current pharmacotherapy for Alzheimer's disease.
Annu Rev Med. 2006;57:513-33. doi: 10.1146/annurev.med.57.121304.131442.
5
Synthesis of nonracemic allylic hydroxy phosphonates via alkene cross metathesis.
J Org Chem. 2004 Dec 10;69(25):8643-51. doi: 10.1021/jo0490090.
6
Stereospecific Pd(O)-catalyzed malonate additions to allylic hydroxy phosphonate derivatives: a formal synthesis of (-)-enterolactone.
J Org Chem. 2004 Apr 16;69(8):2859-62. doi: 10.1021/jo035795h.
7
Stereospecific Pd(0)-catalyzed arylation of an allylic hydroxy phosphonate derivative: formal synthesis of (S)-(+)-ar-turmerone.
J Org Chem. 2003 Nov 28;68(24):9502-5. doi: 10.1021/jo0351318.
8
A new and rapid colorimetric determination of acetylcholinesterase activity.
Biochem Pharmacol. 1961 Jul;7:88-95. doi: 10.1016/0006-2952(61)90145-9.
9
Cyclipostins, novel hormone-sensitive lipase inhibitors from Streptomyces sp. DSM 13381. II. Isolation, structure elucidation and biological properties.
J Antibiot (Tokyo). 2002 May;55(5):480-94. doi: 10.7164/antibiotics.55.480.
10
Cyclipostins: novel hormone-sensitive lipase inhibitors from Streptomyces sp. DSM 13381. I. Taxonomic studies of the producer microorganism and fermentation results.
J Antibiot (Tokyo). 2002 May;55(5):472-9. doi: 10.7164/antibiotics.55.472.
Zotero 插件