在 Camphor-10-Sulfonic Acid,四丁基氟化铵体系中,化学反应生成卡利奇霉素 参考文献:Hitchcock,Stephen A.; Chu-Moyer,Margaret Y.; Boyer,Serge H.,Journal Of The American Chemical Society,1995,Vol. 117,# 21,P. 5750-5756 标题:Hitchcock,Stephen A.; Chu-Moyer,Margaret Y.; Boyer,Serge H.,Journal Of The American Chemical Society,1995,Vol. 117,# 21,P. 5750-5756
专利信息
专利号:US-5442065-A 优先权日:1993-09-09 标 题:Synthesis of tetrahydroquinoline enediyne core analogs of dynemicin 发明人:MAGNUS PHILIP D; ILIADIS THEODORE; EISENBEIS SHANE A; FAIRHURST ROBIN A 权利人:UNIV TEXAS 摘要:A process is described for the preparation of the core azobicyclo[7.3.1]tridecaenediyne moiety of the antitumor antibiotic dynemicin. The synthesis allows efficient production of the enediyne as a stable, compound in good yield from the adamantyl N-protected azabicyclo[7.3.1]tridecadiyne. The adamantyl protecting group is employed in the starting material, N-adamantyl dihydroquinoline or N-adamantyl 6-methoxy quinoline. Also disclosed are process for the synthesis of 3-hydroxy-6-methoxyquinoline and several N-substituted derivatives of azobicyclo[7.3.1]tridecaenediyne. Solid tumor and leukemia assays were performed on the analogs of dynemicin. The results suggest a method that these compounds will useful in treating certain types of leukemias and solid tumors. The disclosed synthesis provides a route to new dynemicin intermediates and analogs which will allow development of second and third generation dynemicins.
专利号:WO-2017100796-A1 优先权日:2015-12-11 标 题 :Modulation of globoseries glycosphingolipid synthesis and cancer biomarkers 发明人:WONG CHI-HUEY; HSU TSUI-LING; WU CHUNG-YI; CHEUNG SARAH K C; CHUANG PO-KAI 权利人:SINACA ACAD; WONG CHI-HUEY; HSU TSUI-LING 摘要:The present disclosure relates to methods and compositions which can modulate the globoseries glycosphingolipid synthesis. Particularly, the present disclosure is directed to glycoenzyme inhibitor compound and compositions and methods of use thereof that can modulate the synthesis of globoseries glycosphingolipid SSEA-3/SSEA-4/GloboH in the biosynthetic pathway; particularly, the glycoenzyme inhibitors target the alpha-4GalT; beta- 4GalNAcT-I; or beta-3GalT-V enzymes in the globoseries synthetic pathway. Additionally, the present disclosure is also directed to vaccines, antibodies, and/or immunogenic conjugate compositions targeting the SSEA-3/SSEA-4/GLOBO H associated epitopes (natural and modified) which elicit antibodies and/or binding fragment production useful for modulating the globoseries glycosphingolipid synthesis. Moreover, the present disclosure is also directed to the method of using the compositions described herein for the treatment or detection of hyperproliferative diseases and/or conditions. Furthermore, the instant disclosure also relates to cancer stem cell biomarkers for disgnostic and therapeutic uses.
专利号:US-10342858-B2 优先权日:2015-01-24 标题 :Glycan conjugates and methods of use thereof 发明人:WONG CHI-HUEY; WU CHUNG-YI 权利人:ACADEMIA SINICA 摘要:The present disclosure is directed to vaccines, antibodies, and/or immunogenic conjugate compositions targeting the SSEA3/SSEA4/GloboH associated epitopes (natural and modified) which elicit antibodies and/or binding fragment production useful for modulating the globo-series glycosphingolipid synthesis. The present disclosure relates to methods and compositions which can modulate the globo-series glycosphingolipid synthesis. Particularly, the present disclosure is directed to glycoenzyme inhibitor compound and compositions and methods of use thereof that can modulate the synthesis of globo-series glycosphingolipid SSEA3/SSEA4/GloboH in the biosynthetic pathway; particularly, the glycoenzyme inhibitors target the alpha-4GalT; beta-4GalNAcT-I; or beta-3GalT-V enzymes in the globo-series synthetic pathway. Moreover, the present disclosure is also directed to the method of using the compositions described herein for the treatment or detection of hyperproliferative diseases and/or conditions.
专利号:US-10590158-B2 优先权日:2015-06-29 标题:Total synthesis of shishijimicin A and analogs thereof 发明人:NICOLAOU KYRIACOS C; LI RUOFAN; LU ZHAOYONG; SOHN TE-IK; WOODS JAMES; PITSINOS EMMANOUIL N 权利人:UNIV RICE WILLIAM M 摘要:In one aspect, the present disclosure provides shishijimicin analogs of the formula: wherein the variables are as defined herein. In another aspect, the present disclosure also provides methods of preparing the compounds disclosed herein. In another aspect, the present disclosure also provides pharmaceutical compositions and methods of use of the compounds disclosed herein. Additionally, antibody drug conjugates of the compounds are also provided.
专利号:US-11465997-B2 优先权日:2017-06-22 标 题 :Synthesis of disorazoles and analogs thereof as potent anticancer agents 发明人:NICOLAOU KYRIACOS C; BELLAVANCE GABRIEL; BUCHMAN MAREK; PULUKURI KIRAN KUMAR; RIGOL STEPHAN 权利人:UNIV RICE WILLIAM M 摘要:In one aspect, the present disclosure provides disorazole analogs of the formula: Formula (I) wherein the variables are as defined herein. In another aspect, the present disclosure also provides methods of preparing the compounds disclosed herein. In another aspect, the present disclosure also provides pharmaceutical compositions and methods of use of the compounds disclosed herein. Additionally, drug conjugates with cell targeting moieties of the compounds are also provided.
专利号:US-7473797-B2 优先权日:2004-04-27 标 题 :Methods of 1,3-enyne preparation using copper (I) catalysts 发明人:VENKATARAMAN DHANDAPANI; BATES CRAIG G; SAEJUENG PRANORM 权利人:UNIV MASSACHUSETTS 摘要:A copper(I) bi-dentate ligand complex-catalyzed procedure for synthesis of 1,3-enynes. The methods and/or systems of this invention afford a variety of enynes, tolerate a variety of sensitive functional groups, and can be employed without resort to expensive palladium reagents.
1: Singh S, Michalska K, Bigelow L, Endres M, Kharel MK, Babnigg G, Yennamalli RM, Bingman CA, Joachimiak A, Thorson JS, Phillips GN Jr. Structural Characterization of CalS8, a TDP-α-D-Glucose Dehydrogenase Involved in Calicheamicin Aminodideoxypentose Biosynthesis. J Biol Chem. 2015 Oct 23;290(43):26249-58. doi: 10.1074/jbc.M115.673459. Epub 2015 Aug 3. 2: Tsodikov OV, Hou C, Walsh CT, Garneau-Tsodikova S. Crystal structure of O-methyltransferase CalO6 from the calicheamicin biosynthetic pathway: a case of challenging structure determination at low resolution. BMC Struct Biol. 2015 Jul 15;15:13. doi: 10.1186/s12900-015-0040-6. 3: Damelin M, Bankovich A, Park A, Aguilar J, Anderson W, Santaguida M, Aujay M, Fong S, Khandke K, Pulito V, Ernstoff E, Escarpe P, Bernstein J, Pysz M, Zhong W, Upeslacis E, Lucas J, Lucas J, Nichols T, Loving K, Foord O, Hampl J, Stull R, Barletta F, Falahatpisheh H, Sapra P, Gerber HP, Dylla SJ. Anti-EFNA4 Calicheamicin Conjugates Effectively Target Triple-Negative Breast and Ovarian Tumor-Initiating Cells to Result in Sustained Tumor Regressions. Clin Cancer Res. 2015 Sep 15;21(18):4165-73. doi: 10.1158/1078-0432.CCR-15-0695. Epub 2015 May 26. doi: 10.1002/bip.22591. doi: 10.1002/cbic.201402489. Epub 2014 Nov 17. doi: 10.1002/cbic.201402119.
合成参考文献
参考文献:10.1006/jmbi.1996.0718 摘要:Kumar RA, Ikemoto N, Patel DJ. Solution structure of the calicheamicin gamma 1I-DNA complex. J Mol Biol. 1997 Jan 17;265(2):187–201. doi: 10.1006/jmbi.1996.0718.