Institute of Chemistry, Academia Sinica – Research
Directions
The research thrusts of the Institute are currently grouped along three major directions: materials chemistry, chemical synthesis and catalysis, and chemical biology. The current topics of materials sector include organic electroluminescent materials and devices, organic field-effect transistor materials and devices, photovoltaic materials and devices. The chemical catalysis and synthesis sector is focusing on the development of new synthetic methodology, drug discovery, carbohydrate chemistry, and the development of new catalytic systems for the generation of renewal energies and green fuels. The chemical biology program has made important advances in the delineation of bio-macromolecular structures and the development of new analytical platforms for disease detection and diagnosis.
Materials Chemistry: Organic Electronic and Optoelectronic Materialsy
Applications of organic optoelectronic materials and molecular engineering of nanomaterials are two major research directions under the materials division. Noticeable results include developments of blue fluorescent molecular materials for high performance organic light-emitting diodes, rational design of field-effective organic memory devices based on pentacene and gold nanoparticles, the very first stable organic thin film transistor based on single crystal of hexacene, rare single-walled metal–organic nanotube (MONT) with a large exterior wall diameter, the applications of metal-organic framework as optoelectronic materials, and a number of high performance materials for efficient solar energy harvesting devices such as dye-sensitized solar cells, perovskite solar cells, or organic photovoltaics. Researchers in this sector also develop stimuli-responsive materials, core-shell nanomaterials, and biomaterials. A recent report shows that a cell membrane–mimicking conducting polymer is capable to integrate biochemical and electrical stimulation to promote neural cellular behavior with great enhancement of neurite outgrowth on this conducting polymer.
Chemical Catalysis and Synthesis: Green Catalysis and Synthetic Methodology
In response to the increasingly demands of sustainable fuel and green synthetic technology, researchers in the organic synthesis and chemical catalysis divisions have strived to advance the development of cutting-edge technology for chemical transformations. The synthetic chemistry division of this sector focuses on the advances of synthetic methodology and drug discovery. The research topics under catalysis division is reconciling to catalysis relating to renewable energy. Major research directions in this sector include: (1) synthetic methodology: silyl ethers for hydroxy- directed nucleophilic acyl alkylation, microwave-assisted carbohydrate synthesis, smart fluorescent probes for bioorthogonal sugar labeling; (2) coordination chemistry: approaching unconventional catalysis via amino-NHC and carbodicarbene, unconventional porphyrin complexes for small molecule activations, engineering cytochrome P450 BM3 and alkane hydroxylase (AlkB) for alkane oxidations; (3) renewable energy catalysis: catalytic hydrogen evolution and mechanistic studies, encapsulated tricopper cluster for methane to methanol conversion, and novel catalysts for valorization of lignocellulosic biomass feedstocks.
Chemical Biology: New Material and Method towards Sustainable Health
Chemical biology division focus on the development of new material and methodology to explore the structure and function of macromolecules associated with cellular function or human diseases. The research activities are directed to unravel the underlying pathological mechanism and to derive new diagnostic and therapeutic strategies. Research topics in this division cover (1) development of smart biomaterials based on novel molecular principles; (2) chemical probe and advanced techniques in bio-imaging and structural biology; (3) drug discovery in cancer, infectious and neurodegenerative diseases; (4) development of structural biology techniques for infectious diseases, and (5) development of advanced proteomics strategies for biomarker discovery. The major achievements from the chemical biology group include the establishment of multiplexed quantitative strategy for membrane proteomics and post-translational modification for delineating disease mechanism and mining therapeutic targets discovery of amyloid fibrils induced from the TDP-43 in the Amyotrophic Lateral Sclerosis (ALS), and development of a photocontrollable probe to induce TDP-43 aggregates in live cells, mapping of the RNA exit channel on transcribing RNA polymerase II by FRET analysis, development of nano velcro chip to capture circulating tumor cells for liquid biopsy, construction of a near-infrared- activatable enzyme platform using an up-conversion nanoparticle to remotely trigger intracellular signal transduction.
利用鋰化矽醚類化合物建構苯環上鄰位羥基之酮類化合物
Lithiation of a Silyl Ether; Formation on an ortho-Fries HydroxyketoneAngew. Chem. Int. Ed. 2014, Early View Article. ( Angew. Chem. Int. Ed. 2014, 53, 1-5)
DOI: 10.1002/anie.201404495R1 and 10.1002/ange.201404495R1
藉由苯環鄰位定向基團的導引，二異丙基氨基鋰可選擇性鋰化烷基矽氧上的 a-質子，繼以發生分子內親核取代反應達成 "矽→碳" 烷基轉移的效果。這個方法突破了長久以來矽醚保護基的單一用途，並開啟矽醚類化合物在有機合成上的新發展。在本研究中，我們進一步拓展此反應的應用性，開發出陰離子性 Snieckus-Fries 重排的延伸反應。此官能基轉換包含了三個重要概念：(1) 利用錯合物引導的概念進行去質子化步驟；(2) a-矽基碳陰離子和醯胺基間進行分子內 Peterson 類型反應；(3) β-含氧矽化物中間體的快速降解。此方法更可進一步應用在天然物合成中，縮短合成路徑以提升合成效率，如 PI3K 抑制劑 LY294002 的合成 (以鄰苯基苯酚為起始物經四步得到 LY294002，總產率 68%)。
The hydroxy-directed nucleophilic acyl alkylation of hydroxyarylamides and salicylic acid through an anionic Si→C alkyl migration was developed using a simple reagent combination of LDA and chlorosilane. The transformation involves (1) a complex-induced proximity effect (CIPE) in the deprotonation step, (2) an intramolecular Peterson type reaction of the resulting a-silyl carbanion with the amide group, and (3) fission of the final β-oxygenated silyl intermediate. This reaction giving silyl ether a new role in organic synthesis was further developed for application to an extended anionic Snieckus-Fries rearrangement. The exceptional functional group transformations achievable using a simple reagent combination of LDA and chlorosilane renders these reactions highly valuable for the synthesis of natural products and medicinally important compounds, such as the PI3K inhibitor LY294002.
Plausible reaction mechanism of the ortho-directed nucleophilic acyl methylation of a hydroxyarylamide (arrows may be considered equilibria) and the D2O quenching experiment.
