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Tianjin, China

Long J.,Nankai University | Ding Y.-H.,Accendatech Company | Wang P.-P.,Nankai University | Zhang Q.,Nankai University | Chen Y.,Nankai University
Journal of Organic Chemistry | Year: 2013

Parthenolide showed extensive bioactivities including selective eradication of AML stem cells. Herein we report protection-free semisyntheses of parthenolide and its cyclopropyl analogue (compound 10) from the abundant natural product costunolide with an overall yield of 55 and 60%, respectively. Compound 10 was more stable than parthenolide, and it maintained comparable activities against AML cell lines and AML stem cells. Therefore, compound 10 might be a superior small molecule than parthenolide as a tool for investigation of cancer stem cell biology. © 2013 American Chemical Society.

Yang Z.-J.,Nankai University | Ge W.-Z.,Nankai University | Li Q.-Y.,Nankai University | Lu Y.,Nankai University | And 8 more authors.
Journal of Medicinal Chemistry | Year: 2015

Inspired by the biosynthesis of sesquiterpene lactones (SLs), herein we report the asymmetric total synthesis of the germacrane ring (24). The synthetic strategy features a selective aldol reaction between β,-unsaturated chiral sulfonylamide 15a and aldehyde 13, as well as the intramolecular α-alkylation of sulfone 21 to construct a 10-membered carbocylic ring. The key intermediate 24 can be used to prepare the natural products costunolide and parthenolide (PTL), which are the key precursors for transformation into other SLs. Furthermore, the described synthetic sequences are amenable to the total synthesis of SL analogues, such as trifluoromethylated analogues 32 and 45. Analogues 32 and 45 maintained high activities against a series of cancer cell lines compared to their parent PTL and costunolide, respectively. In addition, 32 showed enhanced tolerance to acidic media compared with PTL. To our surprise, PTL and 32 showed comparable half-lives in rat plasma and in the presence of human liver microsomes. © 2015 American Chemical Society.

Zhai J.-D.,Nankai University | Li D.,Nankai University | Long J.,Nankai University | Zhang H.-L.,Nankai University | And 4 more authors.
Journal of Organic Chemistry | Year: 2012

The semisynthesis of arglabin, an anticancer drug in clinical application, is developed from abundant natural product parthenolide via three steps. Each step in this sequence is highly stereoselective, and the substrate-dependent stereoselectivity in the epoxidation step can be explained by computational calculations. The success of chemical semisynthesis of arglabin suggests that the biosynthesis of arglabin might proceed in a similar pathway. © 2012 American Chemical Society.

Ma W.-W.,Nankai University | Shi Q.-Q.,Tianjin University of Science and Technology | Ding Y.-H.,Accendatech Company | Long J.,Nankai University | And 2 more authors.
Molecules | Year: 2013

Micheliolide (MCL) derivatives with etherification or esterification of the hydroxyl group at the C4 position were synthesized and evaluated for their activities against different acute myelogenous leukemia (AML) cell lines. These derivatives demonstrated comparable activities against AML cell lines HL-60 and doxorubicin resistant cell line HL-60/A. As to multi-drug resistant AML progenitor cells KG-1a, MCL and some of its derivatives maintained significant activities, and only 1.1-2.7 fold activity reductions were observed when compared with the activities against HL-60, while doxorubicin showed 20-fold activity reduction. Our study demonstrated that the C4 hydroxyl group of MCL might not only be a suitable position for structural modifications, but also be a starting point for the design of appropriate molecular probes to explore the specific targets in the progenitor cell line KG-1a. © 1996-2013 MDPI AG (Basel, Switzerland).

Yang X.-D.,Nankai University | Dong C.-M.,Nankai University | Chen J.,Nankai University | Ding Y.-H.,Accendatech Company | And 4 more authors.
Chemistry - An Asian Journal | Year: 2013

The Tup fragments of tubulysins were synthesized with a tandem reaction as the key step, and unexpected diastereoselectivity was observed in the first Grignard addition stage. The coupling of the enolate of a thiazolyl ketone with chiral sulfinimines furnished the backbone of the Tuv fragment with over 100:1 d.r. and high yield. Thus, tubulysin U and C-4 ep-tubulysin U were prepared in a highly selective and efficient manner. The results of the MTT assay furthermore indicated that C-4 ep-tubulysin U maintained significant growth inhibition activities against several cancer cell lines. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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