Recent Progress in the Synthetic Applications of Substituted Furans and Pyrroles

In this lecture, I would like to present efficient synthetic routes towards the total synthesis of syringolide 1 (2)^1,2 and secosyrin 1 (3),¹ employing 2,4-disubstituted furan 1 as a common precursor. A modified total synthesis of prehispanolone (6)³ from (S)-(+)-Wieland-Miescher ketone (4) via hispanolone (5) will also be discussed. Our methodology for the synthesis of 3,4-disubstituted-lH-pyrroles⁴ and for the generation of 3,4-didehydrothiophene⁵ has also guided us to the successful identification of 1-tert-butoxycarbonyl-3,4-didehydro-1H-pyrrole (7),which is presumably the most strained heterocyclic cumulene ever recorded.     

Liquid crystalline hexa-amides and side chain polysiloxanes of azacrown [18]-N6

The hexa-4-dodecyloxybenzoyl derivative 1 of azacrown [18]-N₆ was originally reported to have a 'tubular' mesophase on the basis of its large central ring and 6-fold symmetry. Starting in the mesophase, annealing of 1 under a cover slip results in formation of a new crystalline phase that melts directly to an isotropic liquid at the temperature previously observed for the mesophase to isotropic transition. Thus the phase behaviour of 1 is kinetically controlled. The analogous hexa-3,4-bisdodecyloxybenzoyl derivative 2 of azacrown [18]-N₆ has no kinetic limitations to its phase changes and has an enantiotropic columnar liquid crystalline phase. We have synthesized side chain copolysiloxanes with a (CH₂)₁₁ spacer and 75-84 per cent by weight of the same 4-dodecyloxybenzoyl-[18]-N₆ mesogen. The polysiloxanes also display a liquid crystalline phase.     

A new series of nematic and smectic liquid crystals with negative dielectric anisotropy: the effect of terminal chain substitution on thermal and electro-optical properties

Two alkyl (1b and 1c) and four fluoroalkyl derivatives (1d-1f) of 4-arylbutyric acid (1c, 1d and 1e) and 4-arylbutanol (1b, 1f and 1g) [aryl = 2',3'-difluoro-4'-(2-(E-4-pentylcyclohexyl)ethyl)-biphenyl-1-yl] were prepared and investigated in the pure form as nematic materials (1b and 1c) and as additives to a ferroelectric liquid crystal (FLC) host (1d-1f). A comparison of 1b and 1c with the decyl analogue 1a demonstrates the effect of terminal chain modification on thermal and electro-optical properties. The substitution of the -CH₂O- (1b) or -COO- (1c) for -CH₂CH₂- in 1a destabilized the N and SmA phases or completely eliminated the smectic behaviour (1c). Dielectric analysis revealed that the chain modification increased the negative Δε, reduced elastic constant K ₁₁ and moderately decreased rotational viscosity γ₁. The temperature dependence of the key electro-optical parameters was analysed for ester 2, the methyl analogue of 1c, which exhibits a 45 K wide N phase. All four fluoroalkyl derivatives 1d-1f showed enantiotropic SmA phases and 1e also exhibited a monotropic SmC phase. Solutions of 1d-1f in a FLC host (0.2 mmol g^-1) increased the tilt angle Θ (up to 45° for 1g), reduced rotational viscosity γ₁ and the risetime τ. The most dramatic changes were observed for 1g, which contains 15 fluorine atoms.     

5＇-Hydroxyzearalenol,a new β-resorcylic macrolide from Fusarium sp. 05ABR26

A new β-resorcylic macrolide, 5＇-hydroxyzearalenol （1）, was isolated from the culture broth of a marine-derived fungus Fusarium sp. 05ABR26. Three known compounds, zearalenone （2）, 8＇-hydroxyzearalenone （3） and zearalenol （4） were also isolated. The structure and relative stereochemistry of 1 were elucidated on the basis of spectroscopic data and single-crystal X-ray diffraction data. Compound 2 displayed potent inhibitory activity against Pyricularia oryzae with a MIC value of 6.25 μg/mL, while compound 3 was much less active; however, 1 and 4 showed no obvious activity.     

Polyoxygenated anti-inflammatory biscembranoids from the soft coral Sarcophyton tortuosum and their stereochemistry

Five novel biscembranoids,ximaolides H-L(1-5),along with four known related compounds(6-9) were isolated from the Hainan soft coral Sarcophyton tortuosum.The structures of the new compounds were determined by extensive spectroscopic analysis,quantum chemical calculations,and/or by comparing their CD spectra with those of the known compounds.Compounds 1 and 2 are the first examples of biscembranoids bearing a 1,35-bridged lactone moiety,4 is the first biscembranoid comprising an uncommon oxetane ring,and 5 represents the first 36-peroxyl biscembranoid.Ximaolides Ⅰ(2),K(4) and F(9) exhibited interesting anti-inflammatory activity by the inhibition of LPS-induced TNF-α protein release in RAW264.7 macrophages.     

Liquid crystalline photoconductors

The influence of molecular order as well as of orientation of charge carrier units on photoconductivity has been investigated for the liquid crystal photoconductors H5T (1), thiadiazole (2) and oxadiazole (3). The discotic H5T (1) and both smectic systems 2 and 3 exhibit a higher photocurrent in the highly ordered mesophase than in the polycrystalline or isotropic state. For 1, results concerning charge carrier transport mechanism and Dember effect are given indicating an electronic charge transport comparable with the one known for single crystalline anthracene.     

Synthesis and properties of optically active 1,3-diols and their derivatives as chiral dopants for ferroelectric liquid crystals

New chiral dopants β-hydroxy ketones 1, 1,3-diols 2, 1,3-dioxanes 3 and 1,3-dioxan-2-ones 4 were designed and synthesized. Reaction of (R)-1,2-epoxyoctane with carbanions derived from 2-(4-substituted phenyl)-1,3-dithianes followed by hydrolysis of the resulting hydroxy dithianes afforded 1. Reduction of 1 gave the diols 2, which yielded 3 upon acetalization and 4 upon carbonation. The syn isomers of 2, 3, and 4 exhibited larger spontaneous polarizations, when applied as chiral dopants, than the anti isomers or hydroxy ketones 1.     

Preparation of silybin 23-esters ability against LPO and and evaluation of their inhibitory DNA protective properties

Twelve 23-esterified silybin derivatives with different patterns of substituents such as aromatic and aliphatic groups (1-12) were designed and synthesized. The antioxidative properties of these compounds were evaluated. The modified silybin analogues exhibited improved inhibitory effects against rat liver homogenate lipid peroxidation compared to silybin, with exception of the trimethoxylated ester (5) and the aliphatic one (9). Compounds 3, 5, 7, 8 and 11 displayed their protective properties on DNA cleavage in a dose-dependent manner.     

Synthesis of Allobetulin, 28-Oxyallobetulin and Related Biomarkers from Betulin and Betulinic Acid Catalysed by Solid Acids

Betulin (1a) is an abundant natural product in the birch bark. Betulin itself currently has little usage. However, allobetulin (2a) has been used as an important intermediate in the further transformation of triterpenoids and as a sample for biological studies.¹ For example, allobetulin was further transformed to a highly active antifeedant for heliothis zea larvae. Some biomarkers (3a,b; 4a,b) with the same or similar structure as ring-E of 2a were identified in a brown coal.³ Consequently, the conversion of 1a to synthetically, biologically and geochemically more important 2a is of great significance. The transformation of 1a to 2a was reported as early as 1922 by Schulze et al in which betulin was isomerized by formic acid, involving formation and hydrolysis of allobetulin formate, to give 2a in moderate yield.⁴     

A Luminescent Metal-Organic Framework with LON Topology for Highly Effective Fluorescence Sensing of Fe3+ and TNP

Aluminescent Ag-based metal-organic framework(1) has been synthesized and its structure has been characterized. Compound 1 was fabricated using the Ag⁺ and bbimb^2‒ ligands and manifestes a rare LON topology. Compound 1 is selective not only in detecting traces of Fe³⁺ and 2,4,6-trinitrophenol(TNP) via luminescence quenching, but also demonstrates high selectivity in the presence of other competitors. Compound 1’s K_sv values towards Fe³⁺ can reach as high as 9.3×10³ L/mol, which is higher than those of several other MOF materials. It is also a recyclable luminous sensor with the potential to be utilized for detecting TNP. Hence, based on its characteristics, compound 1 can be regarded as a prospective luminescence sensor for detecting Fe³⁺ and TNP.     

Synthesis and characterization of new liquid crystalline materials containing a non-activated arylazoindolinobenzospiropyranyl group as a chiral unit. Part II

Two series of new liquid crystalline compounds containing a non-activated arylazoindolinobenzospiropyran, ABP-SPAB 1a-1e (series 1) and SPAP-ABPC 2a-2e (series 2), have been synthesized. These LC dyes were characterized by a differential scanning calorimetry polarizing optical microscopy, X-ray diffraction and electro-optical measurements. All but one of the series 1 compounds examined exhibit monotropic second and/or third transition liquid crystal phases on cooling from the isotropic liquid. In particular, ABP-SPAB 1b shows a monotropic SmC phase, in addition to a SmA phase. In series 2, most of the compounds exhibit a monotropic nematic phase on cooling. SPAP-ABPC 2c forms an enantiotropic nematic phase and a monotropic SmA phase; 2e shows enantiotropic nematic and SmA phases.     

AN EFFICIENT SYNTHESIS OF ALIPHATIC α-ORGANOTHIO ALDOXIME

The importance of the aliphatic α-organothio aldoxime compound 3 in the preparation of various pesticides is well established. Molecules comprising the α-organothio oxime moiety have been reported to exhibit insecticidal,nematocidal,miticidal activities.^[1-2] In the synthesis of the compound 3,the chlorination of the corresponding aliphatic aldoxime 1 is the key step.In conventional methods, the aliphatic aldoxime 1 is chlorinated by chlorine,then the resulting hydroxime acid chloride 2 is treated with sodium alkyl mercaptide to obtain the desired compounds 3^[3]. Although free Cl₂ is the most common chlorinating agent,it is laborious to determine the accurate amount that has been absorbed,and the high reactivity of Cl₂ always leads to side reactions. In connection with an our ongoing research project, we require an efficient and simple method for the synthesis of the compound 3.An improved synthesis process according to the following scheme is reported in this paper.     

Supramolecular Assemblies of Three New Metronidazole Derivatives Constructed with Various Dihydroxy-benzoic Acids via Hydrogen Bonds

Metronidazole(MTZ) is an important antibiotic, which has been widely applied to cure protozoal and bacterial diseases for human beings or animals. Herein, three novel drug supramolecular crystals constructed by MTZ with 2,5-dihydroxy-benzoic acid(2,5-DHBA)(1), 2,6-dihydroxy-benzoic acid(2,6-DHBA)(2) and 3,5-dihydroxy-benzoic acid(3,5-DHBA)(3), respectively, have been discovered. The hydrogen bonds of N-H···O(O-H···N), C-H···O and O-H···O play important roles in the 3D supramolecular framework formation for crystals 1-3. Interestingly, due to the vary locations of the substituent groups, the two-dimensional layers in crystals 1 or 2 are constructed via intermolecular hydrogen bonds between MTZ and 2,5-DHBA or 2,6-DHBA, while in crystal 3 water molecules play a significant role except the intermolecular hydrogen bonds between MTZ and 3,5-DHBA. In addition, five synthons of I R₂²(8), II R₃³(9) in crystal 1, III R₁²(4), IV R₂²(8) in crystal 2 and V R₂²(7) in crystal 3 formed through various hydrogen bonds are founded in this work. Systematic studies of syntheses, crystal structures and thermal analysis are reported.     

Evaluation of carborane-containing nematic liquid crystals for electro-optical applications

Three new structurally similar compounds in series 1[2] and 2 containing 12- and 10-vertex p-carborane units (A and B) were prepared. Their thermal properties were investigated in the pure state and compared to those of their carbocyclic analogues. Using several higher homologues in the series 1[n], clearing temperatures for the unknown 1[4] and 1[10] were predicted. Optical, dielectric and rotational viscosity parameters for carborane derivatives 1[2] and 2 and their cyclohexane analogies were obtained by extrapolation of values measured for 10% solutions in a standard nematic host. The observed trends were rationalised using computed molecular parameters.     

CO2 and photo-controlled reversible conversion of supramolecular assemblies based on water soluble pillar[5]arene and coumarin-containing guest

In this communication,a new supramolecualr amphiphile was successfully constructed based on water soluble pillar[5]arene and a unique guest which contain a CO₂ responsive tertiary amine unit and a UV responsive coumarin group.When guest molecule 1 dispersed in water,it self-assembled into sheet-like structures.Upon bubbling CO₂,1 transformed into 1 H due to the tertiary amine unit was protonated,accompany the nano-sheets transformed into vesicles.Further irradiation of 1 H with 365 nm light for 3 h,the coumarin group reacted with each other to form bola-type amphiphie 2 H.In this case,vesicles collapsed and re-assembled into nano-tubes.However,when addition of WPS into the solution of 1 H,the vesicles transformed into micelles,this is due to the formation of supramolecular amphiphile WP5&1 H.Upon irradiation of WP5&1 H with 365 nm light for 3 h,nano-ribbons observed instead of micelles in the solution.Notably,nanotubes from 2 H could also transform into nano-ribbons after adding WPS.The selfassembly process and the resultant assemblies were characterized by TEM,SEM,DLS,SAXS and NMR technologies.Due to both CO₂ and light are "green" for living organisms,we anticipated our system can offer the possibilities in "on demand" drug absorption and release.     

CONDENSATION REACTION OF α-AROYL-α-ACETYL KETENE CYCLIC DITHIOACETALS WITH AROMATIC ALDEHYDES

As a versatile three-carbon syntho,α-oxoketene cyclic acetals 1 have been applied in many fields. In order to study the structure and application of 1, we performed that α-aroyl-α-acetyl ketene cyclic dithioacetals 2 or 3 condensed with aromatic aldehydes catalyzed by sodium ethoxide and fifteen new condensation products 4 and 5 were obtained.     

Synthesis and cytotoxicity of 28-carboxymethoxy lupane triterpenoids. Preference of 28-O-acylation over 28-O-alkylation of betulin by ethyl bromoacetate

28-Carboxymethoxy lupane tritepenoids 3 and 4 were synthesized by alkylation of betulin with the THP protected 2-hydroxyethyl iodide followed by oxidation and reduction.Direct reaction of betulin (5) or betulone (10) with ethyl bromoacetate led to 28-O-acylation, instead of 28-O-alkylation.The targeted compounds 3 and 4 were not cytotoxic at the highest concentrationtested (75 mmol/L), suggesting that elongation of the chain length at the 28-position in both betulinic acid (1) and betulonic acid (2)was detrimental to the cytotoxicity.The acylation products 28-O-bromoacetates (8a, 8b and 11) and 28-O-methoxyacetate 13exhibited cytotoxicity against several cancer cell lines tested.     

Synthesis and mesomorphic behaviour of novel discotic meso-tetra(3,4,5-n-trialkoxybenzoylaminophenyl)porphyrins

Novel porphyrin derivatives with twelve flexible alkyl chains, namely meso-tetra[4-(3,4,5-n-trialkoxybenzoylamino)phenyl]porphyrins (1a, n = 12; 1b, n = 16) and the zinc complex (2a) were synthesized. The mesomorphic properties were investigated by DSC, WAXD and polarizing optical microscopy; the results showed that 1a and 2a exhibit a pseudo-hexagonal columnar phase, and 1b a rectangular (Col) phase over a wide temperature range including room temperature.     

Anionic Cyclization Approach to Hexahydrobenzo[b] furan-3-one and Hexahydro-1H-3-indolone:Application to Total Syntheses of Natural Products

Hexahydrobenzo[b]furan-3-one(3) and hexahydro-1H-3-indolone (4) are potentially useful intermediates for total synthesis of natural products, such as the hexahydrobenzofuran unit (5) of avermectins and pancracine (6). Anionic cyclization approach toward (3) and (4) have been developed. Their application to the total synthesis of (5) and (6) will be presented.     

A Novel Cyclization of Squalene Initiated by Radical Cation

Squalene 1 is recognized as the precursor of sterols and polycyclic triterpenoids that play important roles in numerous life processes¹. In view of the fact that the cyclization of hexa-1, 5-diene by γ-irradiation² and some isoprenoid polyenes by photochemical method³ through radical cation intermediates have been reported and that tris (p-bromophenyl)ammoniumyl hexachloroantimonate (TBPA⁺SbCl₆, 2) could oxidize olfines to the corresponding radical cations that underwent pericyclic reactions⁴, we thought it might be worthwhile to try the biomimetic cyclization of squalene initiated by radical cations. Previously we⁵ have reported the cyclization of geraniol and nerol to cis-p-mentha-2,8-dien-l-ol by reaction with 2. Herein, we report the cyclization of 1 initiated by 2 in dry dichloromethane to give 20-R-protosta-5,24-diene 3a and 20-S-protosta-5,24-diene 3b in the ratio of 1:1 with the total yield of 20%(Scheme 1).