行政院國家科學委員會專題研究計畫 成果報告
鐵錯合物及雙烯雙酮之合成應用.DNA 凹槽化合物之合成.液
晶及感應化合物的合成(3/3)
計畫類別： 個別型計畫 計畫編號： NSC91-2113-M-110-010- 執行期間： 91 年 08 月 01 日至 92 年 07 月 31 日 執行單位： 國立中山大學化學系(所) 計畫主持人： 王志偉 計畫參與人員： 賴銘智、廖淑岐、王漢明、韓政良、孫忠賢、劉秉豪、黃晟瑋 報告類型： 完整報告 報告附件： 出席國際會議研究心得報告及發表論文 處理方式： 本計畫可公開查詢中 華 民 國 92 年 11 月 3 日
Abstract
I. Hexaazatriphenylene nucleus (HAT)
The hexaazatriphenylene nucleus (HAT) is considered an electron deficient heterocycle. Many useful macroscopic properties of naterials can be engendered by the molecular organization of the disc-like nature of HAT. Furthermore, HAT contains three bidentate binding sites for metal and can be studied in the context of catalyst. We have successful synthesized a wide variety of new HAT derivatives; (1) monofuntionalized HAT-Alkoxy derivatives, (2) difunctionalized HAT-alkoxy-nitrile derivatives, (3) monofunctionalized HAT-polyether derivatives and (4) monofunctionalized HAT-crown ether derivatives.
Liquid Crystal: Monofunctionalized HAT-alkoxy derivatives were found
were readily synthesized by the condensation of hexaketocyclohexane with 4,5-dialkoxy-1,2-diaminobenzene. Polarization microscopy and DSC studies showed all compounds to exhibit very wide mesophase range of over 150 oC. A hexagonal columnar mesophase was assigned for the compounds and an additional rectangular phase was also observed for the certain hexyloxy derivative, as determined by X-ray diffraction measurements. Incorporation of alkoxy chains provides dispersive forces and reduction of electron deficiency of the HATN core to enforce columnar arrangements in the mesophase. (1. Chi Wi Ong, Su-Chih Liao, Tsu Hsing Chang, Hsiu-Fu Hsu - Rapid synthesis of new discotic liquid crystals based on diquinoxalino[2,3-a:2’3’-c]phenazine containing hexakis(alkoxy) side arms.
Tetrahedron Letts, 2003, 44, 1477; 2. Chi Wi Ong,* Su-Chih Liao, Tsu Hsing Chang,
Hsiu-Fu Hsu - Mesogenic Properties of the Electron Deficient Discotic Hexakis(alkoxy)hexaazatrinaphthylene Compounds, Submitted to Liquid Crystals, 2003, Oct). 1. Synthesis of hexaketocyclohexane. OH OH OH OH HO HO 1. HNO3 (65%) 2. NaHCO3 ONa OH O HO NaO O O O O O O HNO3 (25%) O O2 Na2SO3 H H O O
2. Synthesis of HAT-derivatives
The synthesis of chiral side chains and difunctionalized HAT-alkoxy compound has also been achieved and these will be published elsewhere.
Solid State π-Complexation: The control of solid-state assembly is of current
interest. For example, second-order nonlinear optic response by a crystal requires noncentrossymnmetry, engineering the necessary solid-state ordering. Bulk conductivity is likewise related to solid stat structure. HAT nucleus has been recently studied in the context of second order nonlinear optic and conducting material. The electron deficient HAT nucleus would be predisposed to avoid self π-complexation in the solid state. To date only the HAT-hexaamide appeared uniquely capable of associating via hydrogen bonding in the solid sate.
We have successfully synthesized the first bifunctional HAT derivative containing a donor and acceptor groups, HAT-CN-OMe. Interestingly, the X-ray structure of HAT-CN-OMe revealed rigorous stacking and HAT-HAT π-complexation in the solid state. This stands in contrast to the corresponding electron deficient, which exhibit rigorous avoidance of HAT-HAT π-complexation in the solid state. The introduction of three methoxy groups in HAT-CN-OMe has dramatic consequences upon the stability of the resulting π-complexation of these compounds in the solid state. We believed that the presence of alkoxy group in electron deficient HAT has over-ride the avoidance of π-complexation. The molecules are packed in a staggered ABAB layer arrangement with an offset of one of the molecular centers from the stacking axis. The mean interplanar distance of 3.27 Å between HAT rings is smaller than the van der Waals sum of 3.54 Å13 and is consistent with π-complexation. This is the first truly non-covalent supramolecular assembly for the HAT nucleus through
π-complexation in the solid state. (Intramolecular Electronic Interaction and Enforced Solid State π-Complexation in Hybrid Donor- Acceptor 1,4,5,8,9,12- Hexaazatriphenylene Tsu-Hsin Chang, Pi-Ju Wu, Michael Y. Chiang, Su-Chih Liao,
Chi Wi Ong, submitted to Angew. Chem. 2003, Oct.)
OR OR H2N H2N N N N N N N OR OR RO RO OR O O O O O O 8 H2O cat.H+, EtOH OR
CN H2N H2N N N N N N N R R R R R R O O O O O O 8 H2O CH3OH/ CH3CN CN + N N N N N N CN OCH3 NC OCH3 CN H3CO 1. R = CN 2. R = COOH 3. R = COOCH3 4. R = CON(CH3)2 5. R = CONH2 6 AcOH
Enzyme Model and Sensor: We have completed the synthesis of tris-crown
ether containing diquinoxalino-[2,3-a:2’3’-c]phenazine and study its ability to behave has sensor for specific cations (Na, Li, K). Furthermore, we have also completed the synthesis of hexakis(polyether)diquinoxalino-[2,3-a:2’3’-c]phenazine that is water soluble. Further studies on its properties as RNAase is underway.
Others: The synthesis of 3,4-diamino-thiophene has finally been achieved and
its condensation with hexaketonecyclohexane give insoluble solid. When dissolved in TFA, the compound was found to emit orange-red light at U.V-long wavelength. Effort has been carried out to synthesized 2,5-disubstituted-3,4-diamino-thiophene for condensation with hexaketonecyclohexane in the hope of improving solubility.
II. Diene-Dione In Synthesis
A variety of 1-amino-alkyl ester and nitrile reacts with diene-dione to give pyrrole derivatives, and under mild basic condition undergo further intramolecular condensation to give pyrrolizine and indolizine derivatives. (Heterocycles, 2002, 57, 1303). Bayer (in Germany) has shown great interest in these compounds as crop protection.
2-Methoxy- and 2-trimethylsilyloxyfuran undergo facile ring opening reaction with metal carbene to afford (2Z,4E)-hexadienedioate and mono-protected (2Z, 4E)-muconic acid derivatives (P. C. Shieh; C. W. Ong; Metal carbenoid mediated ring opening of furan-2-yloxy derivatives. Stereoselective synthesis of 2,4-hexadienedioic acid and 6-aryl-1-oxo-2,4-hexadienoic acid derivatives,
Tetrahedron, 2001, 57, 7303)
Dienediones have also been found to possess antimicrobial and antitumor activity. More interesting, dienediones have been found to possess vasorelaxing activity of the first time.
III. DNA Groove Binding Agents
We have shown that unfused bithiophene pyrimidine derivatives having electrostatic groups binds to DNA strongly and possesses antitumor activity (Y. M. Chou, M. C. Lai, T. M. Hwang, C. W. Ong, Synthesis and Antitumor Activity of Bithienyl-Pyrimidine Derivatives with Electrostatic Binding Side Chains, Bioorg.
Med. Chem. Lett. 1999, 9, 2643). Efforts have been carried out to synthesize branch
chain (dendrimer like) electrostatic binding groups on groove binding agent and study the influence of sequence specificity on DNA binding. Footprinting has been carried out and preliminary result showed a difference in the sequence specificity for straight chain and branch chain electrostatic binding group. Improve cytotoxicity was also observed.
Some new groove-binding agents synthesized are shown below and results will be published soon. S H N O N H N O N S H N O N H N O N S H N O N H N O N N S H N O N H N O N S H N O N H N O N S H N O N H N O N N H N O N H N O N H N O N H N O N H N O N H N O N
IV. Iron Complexes
A review entitled "Triene-tricarbonyliron complexes in organic synthesis"
(Trends in Organometallic Chemistry, Vol.4, 2002, 47-58) illustrates our effort in establishing the new synthetic application of organoiron complexes.
OMe COOH Birch reduction OMe COOH CH2N2, Et2O OMe COOMe PTS, CH2Cl2 OMe COOMe + OMe COOMe major Fe(CO)5, n-Bu2O OMe COOMe Fe(CO)3 p-methoxyphenylacetic acid
Preparation of iron complex:
THF OMe CH2OH Fe(CO)3 DIBAL DEAD, PPh3 Phthalimide, THF OMe CH2NPhth Fe(CO)3 Ph3CClO4 OMe CH2NPhth Fe(CO)3 ClO4 -TMSCN CH2Cl2, reflux OMe CH2NPhth Fe(CO)3 NC 1. Me3N O 2. Hydrazine, MeOH 3. Oxalic acid, MeOH-H2O
4. NaHCO3 O NC NH (BOC)2O, DMAP Et3N, CH2Cl2 O NC NBOC
O NC NBOC 1. Base 2. TMSCl OTMS NC NBOC + OTMS NC NBOC Separation H+ OTMS NC NBOC Pb(OAc)4 O NC NBOC Knochel reagent EtO2CCH2Cu(CN)ZnI O NC NBOC EtO2C Hydrogenation O NBOC N O
Synthesis Of Functionalized [2,5]-Octane OCH3 Fe(CO)3 R1 R2 OCH3 Fe(CO)3 R1 R1 R R 1a R=H 1b R=CH3 + OCH3 R R R1 2 3 OCH3 R R + 4 OMe CH2OH
Fe(CO)3 (Ac)2O, DMAP
Et3N, CH2Cl2 OMe CH2OAc Fe(CO)3 Ph3CClO4 OMe CH2OAc Fe(CO)3 ClO4 -TMSCN CH2Cl2, reflux OMe CH2OAc Fe(CO)3 NC CoCl26H2O NaBH4, MeOH OMe CH2OAc Fe(CO)3 H2NH2C N O O O CHN2 O Et3N, CH2Cl2 OMe CH2OAc Fe(CO)3 CHN2 N H O Rh2(OAc)4 OMe CH2OAc Fe(CO)3 N H O O NBOC N H O
Keywords HAT- derivatives, liquid crystal, solid state π-complexation, sensor, enzyme model, diene-dione, iron-tricarbonyl complex, Mazamine, goove binding agents, branched electrostatic group.
