154456-41-4Relevant academic research and scientific papers
Total Syntheses and Biological Activities of Vinylamycin Analogues
Bai, Fang,Chen, Yue,Ding, Yahui,Guo, Xiaoqian,Jiang, Shende,Kuang, Beijia,Li, Chun-Qi,Li, Jiangnan,Li, Luyuan,Liu, Jianwei,Liu, Ying,Wang, Jinghan,Wang, Liang,Xia, Bo,Yang, Guang,Zhang, Quan,Zhu, Xiao-Yu
, p. 1189 - 1209 (2017)
Natural depsipeptide vinylamycin was reported to be an antibiotic previously. Herein we report vinylamycin to be active against K562 leukemia cells (IC50 = 4.86 μM) and be unstable in plasma (t1/2 = 0.54 h). A total of 24 vinylamycin analogues with modification of the OH group and chiral centers were generated via a combinatorial approach. The lead compound 1a was subsequently characterized as having the following: no antimicrobial activity, significantly higher plasma stability (t1/2 = 14.3 h), improved activity against K562 leukemia cells (IC50 = 0.64 μM), and up to 75% cell inhibition without significant toxicities in K562 cells xenograft zebrafish model. Furthermore, compound 1a maintained its activity against the breast cancer cell line MCF-7 under hypoxic conditions. In comparison, the activity of gemcitabine in the same hypoxic in vitro model of MCF-7 cells was 15-fold lower. Therefore, the present results demonstrate that 1a has great potential as an anticancer agent.
New Spisulosine Derivative promotes robust autophagic response to cancer cells
Chaturvedi, Priyank,Datta, Dipak,Ganesher, Asha,Meena, Sanjeev,Mitra, Kalyan,Panda, Gautam,Sahai, Rohit
, (2020/01/13)
Therapy resistance by evasion of apoptosis is one of the hallmarks of human cancer. Therefore, restoration of cell death by non-apoptotic mechanisms is critical to successfully overcome therapy resistance in cancer. By rational drug design approach, here we try to provide evidence that subtle changes in the chemical structure of spisulosine completely switched its cytotoxic function from apoptosis to autophagy. Our most potent molecule (26b) in a series of 16 synthesized derivatives showed robust autophagic cell death in diverse cancer cells sparing normal counterpart. Compound 26b mediated lethal autophagy induction was confirmed by formation of characteristic autophagic vacuoles, LC3 puncta formation, upregulation of signature autophagy markers like Beclin and Atg family proteins. Altogether, we have detected novel autophagy inducer small molecule which can be tested further for drug discovery research.
Studies toward the synthesis of (-)-zampanolide: Preparation of the macrocyclic core
Troast, Dawn M.,Yuan, Jiayi,Porco Jr., John A.
scheme or table, p. 1701 - 1711 (2009/07/18)
Studies towards the synthesis of the macrocyclic core of (-)-zampanolide are reported. The synthetic approach features a one-pot reduction/vinylogous aldol reaction for construction of the C-15-C-20 fragment, an intramolecular silyl-modified Sakurai (ISMS) reaction for construction of the 2,6-cis-disubstituted exo-methylene pyran subunit, and use of an sp 2-sp3 Stille reaction for macrocyclization.
(+)-Saxitoxin: A first and second generation stereoselective synthesis
Fleming, James J.,McReynolds, Matthew D.,Du Bois
, p. 9964 - 9975 (2008/03/17)
A stereoselective synthesis of the bis-guanidinium toxin (+)-saxitoxin (STX), the agent infamously associated with red tides and paralytic shellfish poisoning, is described. Our approach to this unique natural product advances through an unusual nine-membered ring guanidine intermediate 39 en route to the tricyclic skeleton that defines STX. The effectiveness of this strategy is notable, as only four steps are needed to transform 39 into the target molecule, including a four-electron alkene oxidation catalyzed by OsCl3. Construction of the critical monocyclic guanidine has been achieved through two channels, the first of which makes use of Rh-catalyzed C-H amination and highlights a novel class of heterocyclic N,O-acetals as iminium ion equivalents for crafting functionalized amines. A second route to 39 relies on a stereoselective acetylide dianion addition to a serine-based nitrone, thereby facilitating the preparation of STX in just 14 linear steps from commercial material.
Stereoselective synthesis of 2-substituted 3-azabicyclo[3.2.0]heptan-2-ones by [2+2]-cycloaddition of N-allyl-β-N-keteniminium salts derived from (R)-vinylglycinol
Delle Monache, Giuliano,Misiti, Domenico,Salvatore, Patrizia,Zappia, Giovanni,Pierini, Marco
, p. 2653 - 2659 (2007/10/03)
A stereoselective synthesis of (1R,2R,5S)-2-benzyloxymethyl-3-azabicyclo[3.2.0]heptan-2-one was achieved, by intramolecular [2+2]-cycloaddition of (R)-vinylglycinol-derived N-allyl-β-N-keteniminium salts, with high facial diastereoselection. The regio- an
Stereoselective synthesis of N-boc-galantinic acid ethyl ester
Kumar,Datta
, p. 1381 - 1384 (2007/10/03)
An efficient synthesis of the biologically important title amino acid is described. The key features of the synthesis are, i) a chelation controlled Grignard reaction towards stereoselective formation of the syn-1,2-amino alcohol unit, and ii) construction of the anti-1,3-diol moiety via hydroxy group directed stereoselective reduction of a proximal ketone.
Synthesis of chiral vinylogous sulfonamidopeptides (vs-peptides)
Gennari, Cesare,Longari, Chiara,Ressel, Stefano,Salom, Barbara,Mielgo, Antonia
, p. 945 - 959 (2007/10/03)
Chiral vinylogous amino sulfonic acids (vs-amino acids) were synthesized starting from either L- or D-α-amino acids via N-Boc-α-amino aldehydes. Wittig-Horner reaction with methyl (or ethyl) diethylphosphoryl methanesulfonate and nBuLi gave the corresponding α,β-unsaturated sulfonates in high yield and complete (E) stereoselectivity. Cleavage of the methyl (ethyl) ester was effected by treatment of the sulfonates with nBu4NI in refluxing acetone. Treatment of the nBu4N+ sulfonate salts with SO2Cl2/PPh3/CH2Cl2 gave the corresponding sulfonyl chlorides as stable chromatographable compounds. The synthetic sequence proved successful not only starting from α-amino acids carrying unfunctionalized side-chains (Ala, Val, Phe, Leu, Pro), but also with functionalized α-amino acids (Ser, Tyr, Gln) provided that the side chains were suitably protected. The sulfonyl chlorides were coupled with the amine salts to give vs-dipeptides. Amine hydrochlorides were prepared from N-Boc derivatives by treatment with HCl in methanol or ethyl acetate. The process was further iterated to give vstripeptides and vs-tetrapeptides. The above procedure was also used to synthesize "mixed" peptides, which incorporate both proteinogenic α-amino acids and vs-amino acids. Proteinogenic α-amino acids were incorporated at both the C-terminal and the N-terminal position.
Tunable Stereoselectivity in the Addition of 2-Lithiothiazole to L-Serinal Derived N-Benzyl Nitrone. Synthesis of C-2 Epimer 2,3-Diamino-4-Hydroxybutanals
Dondoni, Alessandro,Merchan, Francisco L.,Merino, Pedro,Tejero, Tomas,Bertolasi, Valerio
, p. 1731 - 1734 (2007/10/02)
A complete reversal of diastereoselectivity (ds 95percent) in the addition of 2-lithiothiazole to L-serinal derived N-benzyl nitrone has been achieved by the change of the hydroxy and amino protective groups in the aldehyde moiety; the resultant epime
