Synthesis of fluorinated analogues of the immunosuppressive drug FTY720

Four fluorinated derivatives of the immunosuppressive drug FTY720 were synthesized by a convergent strategy, using the Sonogashira coupling as the key reaction to assemble the two major fragments. © 2011 Elsevier Ltd. All rights reserved.link_to_subscribed_fulltex

Desymmetrizations of meso oxabicyclic compounds by asymmetric C-H insertion

meso Oxabicyclo[3.2.1]diazoketones underwent intramolecular C-H bond insertion to generate oxatricyclic compounds bearing fused cyclopentanones upon reaction with rhodium catalysts. Using the chiral catalyst Rh 2(S-BPTTL)4, 44% ee was achieved in this desymmetrization reaction. © 2003 Elsevier Ltd. All rights reserved.link_to_subscribed_fulltex

Allenes as dipolarophiles in the intramolecular carbene cyclization-cycloaddition cascade reaction

Intramolecular carbene cyclization-cycloaddition cascade reactions with allenes occur efficiently in the presence of dirhodium catalysts to afford oxatricyclic products as single diastereomers. © Georg Thieme Verlag Stuttgart.link_to_subscribed_fulltex

A tandem metal carbene cyclization-cycloaddition approach to the pseudolaric acids

An approach toward the synthesis of the antifungal and cytotoxic pseudolaric acids based on the tandem metal carbene cyclization-cycloaddition reaction is described. Using this strategy, the advanced intermediate 3a bearing three of the four stereocenters of the target molecules has been synthesized. The substrate-controlled diastereoselectivity of the tandem carbene cyclizationcycloaddition was preferential for the undesired diastereomer, but reagent control through the use of Hashimoto's chiral rhodium catalyst Rh 2(S-BPTV) 4 reversed the selectivity in favor of 3a. Ring opening of the oxabicyclic nucleus to give a hydroxycycloheptene has been demonstrated in a model study.link_to_subscribed_fulltex

Alisol B, a novel inhibitor of the sarcoplasmic/endoplasmic reticulum Ca2+ ATPase pump, induces autophagy, endoplasmic reticulum stress, and apoptosis

Emerging evidence suggests that autophagic modulators have therapeutic potential. This study aims to identify novel autophagic inducers from traditional Chinese medicinal herbs as potential antitumor agents. Using an image-based screen and bioactivity-guided purification, we identified alisol B 23-acetate, alisol A 24-acetate, and alisol B from the rhizome of Alisma orientale as novel inducers of autophagy, with alisol B being the most potent natural product. Across several cancer cell lines, we showed that alisol B-treated cells displayed an increase of autophagic flux and formation of autophagosomes, leading to cell cycle arrest at the G1 phase and cell death. Alisol B induced calcium mobilization from internal stores, leading to autophagy through the activation of the CaMKK-AMPK-mammalian target of rapamycin pathway. Moreover, the disruption of calcium homeostasis induces endoplasmic reticulum stress and unfolded protein responses in alisol B-treated cells, leading to apoptotic cell death. Finally, by computational virtual docking analysis and biochemical assays, we showed that the molecular target of alisol B is the sarcoplasmic/endoplasmic reticulum Ca2+ ATPase. This study provides detailed insights into the cytotoxic mechanism of a novel antitumor compound. ©2010 AACR.link_to_OA_fulltex

Review of Newly Registered Oncology Drugs in Hong Kong

Erratum in v. 23 n. 4, p. 151: It should be 'EWIG, Celeste Lom Ying' instead of 'EWING, Celeste Lom Ying'.link_to_OA_fulltex