Hui-Chang Lin

exo-Glycal chemistry: general aspects and synthetic applications for biochemical use.

It is well known that carbohydrates play an indispensable role in a variety of essential biological activities, such as cell-cell adhesion, bacteria and virus infections, and tumor metastasis. Among an increasing number of sugars and sugar mimetics that have been designed and synthesized for the purpose of drug discovery, C-glycosides are considered to be one of the best choices on account of their stability and resemblance as they differ from normal glycosides only in glycosidic linkages. exo-Glycals are unsaturated sugars that have a double bond attached to the anomeric center outside the sugar ring. These carbohydrate molecules are useful for the synthesis of C-glycosides and compounds containing quaternary carbons, provided that the olefin can be properly reduced or functionalized. This review places special emphasis on two aspects of exo-glycals including general methods of preparation and synthetic applications for making biologically important molecules. The first half discusses the methods of addition/elimination and Ramburg-Bäcklund rearrangement that offer many beneficial features including a wide range of double bond substitutions, limited reaction steps, easy operation and good overall yields. The rest of the article demonstrates a number of synthetic studies using exo-glycals as the starting materials. The target molecules can be categorized into three groups, namely C-glycosides, enzyme inhibitors and bioactive natural products.

Stereoselective Synthesis of Spiro Bis-C,C-α-arylglycosides by Tandem Heck Type C-Glycosylation and Friedel–Crafts Cyclization

Spiro bis-C,C-α-arylglycosides were synthesized in three steps in 78-85% overall yields starting from exo-glycals. The initial Heck type C-aryl addition of exo-glycals with arylboronic acids afforded α-aryl-β-substituted C-glycosides with exclusive α-stereoselectivity. Among the products, β-ethanal α-aryl C-glycosides further reacted with alkylthiol in the presence of InCl3, followed by in situ Friedel-Crafts cyclization to yield the desirable final products. We proposed a mechanism to explain how the α-aryl group serves as a main determinant of the cyclization.

Pculin02H, a curcumin derivative, inhibits proliferation and clinical drug resistance of HER2-overexpressing cancer cells.

Amplification of the HER2 gene (also known as neu or ErbB2) or overexpression of HER2 protein has become a solicitous therapeutic target in metastatic and clinical drug-resistance cancer. In our present work, a new series of curcumin derivatives were designed and synthesized using curcumin as model. Here, we evaluated whether curcumin derivatives have better efficiency to degrade HER2 than curcumin. Among these test compounds, pculin02H had better efficiency to inhibit the expression of HER2 than curcumin. Moreover, pculin02H preferentially suppressed the growth of HER2-overexpressing cancer cell lines. Pculin02H induced G2/M cell cycle arrest followed by apoptosis. Interestingly, our results suggested that a posttranslational mechanism contributed to pculin02H-induced HER2 depletion in HER2-overexpressing cancer cells. We found that pculin02H significantly enhanced the antitumor efficacy of clinical drugs on HER2-overexpressing cancer cells as well as efficiently reduced HER2-induced drug resistance. These findings may provide an alternative preventive or therapeutic strategy against HER2-overexpressing cancer cells.

Synthesis and Characterization of Soluble Conjugated Poly(p-phenylenevinylene) Derivatives Constituted of Alternating Pyrazole and 1,3,4-Oxadiazole Moieties

New soluble poly(p-phenylenevinylene) derivatives with 1,3,4-oxadiazole and pyrazole rings along the main chain were synthesized by Heck coupling. The new conjugated polymers are soluble in common organic solvents as a result of the fully conjugated backbone with dodecyloxy side groups. The polymers show relatively high glass-transition temperatures (up to 160°C) and good satisfactory thermal stability. Solutions of the polymers emit blue-greenish light with photoluminescence (PL) emission maxima around 490–500 nm. The PL spectrum of the polymer’s thin films, with a maximum at 515 nm, shows a red-shift (~20 nm), with respect to the solution spectrum. Cyclic voltammetry reveals that both conjugated polymers have reversible oxidation and irreversible reduction, making them n-type electroluminescent materials. The electron affinity of the new polymers was estimated as 2.73–2.74 eV. The weight-average molecular weights (M w) of the new soluble polymers were in the range of 4790–4950.