Synthetic Diphenylacetylene-Based Retinoids Induce DNA Damage in Chinese Hamster Ovary Cells without Altering Viability

All-trans-retinoic acid (ATRA), the active metabolite of vitamin A, plays a pivotal role in cell differentiation, proliferation and embryonic development. It is an effective therapy for dermatological disorders and malignancies. ATRA is prone to isomerization and oxidation, which can affect its activity and selectivity. Novel diphenylacetylene-based ATRA analogues with increased stability can help to overcome these problems and may offer significant potential as therapeutics for a variety of cancers and neurodegenerative diseases, including amyotrophic lateral sclerosis. Here, we investigated the effects of these retinoids on cell viability and genotoxicity in the widely used model system of the rapidly proliferating Chinese hamster ovary cell line. DC360 is a fluorescent ATRA analogue and DC324 is a non-active derivative of DC360. EC23, DC525, DC540, DC645, and DC712 are promising analogues with increased bioactivity. The cytotoxic activity of the compounds was evaluated by ATP assay and DNA damage was tested by comet assay. No cytotoxicity was observed in the 10⁻⁶–10⁻⁵ M concentration range. All compounds induced DNA migration similar to ATRA, but DC324, DC360 and EC23 did so to a greater extent, particularly at higher concentrations. We believe that retinoid receptor-independent genotoxicity is a general characteristic of these compounds; however, further studies are needed to identify the molecular mechanisms and understand their complex biological functions.     

Synthesis of a New C-15 Phosphorus Ylide Used for the Preparation of Some β-End-Group Retinoid Derivatives

A synthesis of a new C-15 phosphorus ylide from a C-14 enaminone is reported. This reagent, which undergoes selective 1,2- or 1,4-additions with saturated and unsaturated aldehydes, may find some synthetic use for the preparation of β-end-group retinoid derivatives.     

新法合成乙炔型维A酸

合成了一种新型乙炔型维A酸类化合物, 拓展了该类碘代芳香羧酸与苯乙炔直接偶联的无铜 Sonogashira 反应. 以对溴苯甲酸为底物, 研究了无铜条件下PdCl2(PPh3)2的催化性能, 在10倍量的哌啶中, 对溴苯甲酸、苯乙炔和摩尔分数为4%的PdCl2(PPh3)2在85 ℃下反应20 min得到99%的偶联分离产率, 总收率72%. 本方法也适用于相关乙炔型RAs 分子的合成, 具有操作简单、产率高等优点.     

Heterocycle-bridged and Conformationally Constrained Retinoids: Synthesis of 4-(7,8,9,10-Tetrahydro-7,7,10,10-tetramethyl-4H-benzo[6,7]chromeno-[4,3-d]thiazole-2-yl)benzoic Acid

Retinoids are a class of synthetic and natural compounds structurally related to retinoic acid. In a search for discovery of a new class of heterocycle‐bridged and conformationally constrained retinoids, here we report the synthesis of 4‐(7,8,9,10‐tetrahydro‐7,7,10,10‐tetramethyl‐4H‐benzo[6,7]chromeno[4,3‐d]thiazole‐2‐yl)benzoic acid ( 10 ) starting from 5,6,7,8‐tetrahydro‐5,5,8,8‐tetramethylnaphthalen‐2‐ol ( 13 ). Several approaches was attempted to obtain target compound 10 . Structure elucidation of synthesized compounds has been made on the basis of elemental analysis and spectral data (¹H NMR, IR and MS).     

Design and synthesis of α-aminonitrile-functionalized novel retinoids

We have developed an expedient one-pot method for the synthesis of α-aminonitrile-functionalized new retinoids via a three-component condensation of β-cyclocitral, amine, and TMSCN (trimethyl silylcyanide) in the presence of a catalytic amount of indium(III) chloride in water. The reactions proceeded smoothly at room temperature in water to generate the corresponding retinoids in moderate to excellent yields (85–92%). In addition, the utility of this reaction was demonstrated to synthesize boron-containing retinoids.     

Complete assignments of the 1H and 13C NMR spectra of 9,10-didehydro retinoic acids

A new class of retinoic acids was synthesized containing a 9,10-rigid bond. 1H and 13C NMR spectra were assigned for eight new compounds (all-E, 13Z) containing a carboxylic acid or tertiobutylester polar end group. Assignments were based on the combination of one- and two-dimensional experiments (APT, COSY, HMBC).     

Boron-containing novolac resins as flame retardant materials

Boron-containing novolac resins were prepared from novolac resins and bis(benzo-1,3,2-dioxaborolanyl)oxide and bis(4,4,5,5-tetramethyl-1,3,2-dioxa-borolanyl)oxide. The reaction of the model compound 2,6-dimethylphenol with these organoborates was complete but when the novolac resin was reacted, the degree of modification was moderate, even when there was an excess of boron compounds. The thermal degradation was investigated by TGA and pyrolysis, collecting volatiles which were investigated by GC-MS analysis, and the various compounds detected at different degradation temperatures were shown. The thermal degradation under air showed that the presence of boron is significant in the residue at high temperature. LOI values were high. Correlations between the high char yields and LOI values mean that the flame retardancy of the novolac resins improves when they are modified with bis(benzo-1,3,2-dioxaborolanyl)oxide.     

Synthesis of 11‐cis‐Retinoids by Hydrosilylation–Protodesilylation of an 11,12‐Didehydro Precursor: Easy Access to 11‐ and 12‐Mono‐ and 11,12‐Dideuteroretinoids

An expeditious, highly efficient approach to 11‐cis‐retinoids was achieved by semihydrogenation of a readily available 11‐yne precursor through a hydrosilylation–protodesilylation protocol. The complete chemo‐, regio‐, and syn‐stereoselectivity of the method also allowed direct access to 11‐ and 12‐monodeutero‐, and 11,12‐dideutero‐11‐cis‐retinoids. The analogous trans series was not accessible by this route, and was synthesized by means of Hiyama coupling.     

Polyhedral monocarbaborane chemistry : Reactions of the [6-Ph-nido-6-CB9H11] anion with two-electron donors to yield a series of neutral arachno and closo ten-vertex monocarbaborane derivatives

Reaction of the ten-vertex [6-Ph-nido-6-CB₉H₁₁]⁻ anion (1) with two-electron donor ligands L, where L is SMe₂, NH₂Ph, NC₅H₅, NC₅H₄-para-CH₂Ph, NC₅H₄-para-Ph or NC₉H₇ (where NC₉H₇ is quinoline) in the presence of {FeCl₃(OH₂)₆} gives the six neutral arachno ten-vertex monocarbaboranes [6-Ph-9-L-arachno-6-CB₉H₁₂], compounds 2, 3, 4, 7, 9 and 11, respectively, isolatable in yields of up to 63%. On prolonged treatment with {FeCl₃(OH₂)₆} oxidative cluster closure of the four compounds 4, 7, 9 and 11 that have pyridine-type ligands gives the neutral closo ten-vertex monocarbaboranes [1-Ph-6-L-closo-1-CB₉H₈], compounds 6, 8, 10 and 12, respectively, in yields of 49-92%. All new species 2, 3, 4, 6, 7, 8, 9, 10, 11 and 12 are characterised by single-crystal X-ray diffraction analysis and NMR spectroscopy. [This paper is an annotated exposition of parts of an oral presentation at the Third Pan-European Meeting of Boron Chemists, EUROBORON-3, Pruhonice, The Czech Republic, September 2004, of which the proceedings constitute this volume of Journal of Organometallic Chemistry.]     

改性酚醛成炭剂的制备及其在氢氧化镁/聚酰胺6阻燃体系中的协效阻燃作用

氢氧化镁(MH)是一种重要环保型阻燃剂,针对MH阻燃效率低,添加量大,与树脂相容性差的特点,研制了硼改性酚醛基成炭剂(BPF)用于增强MH的凝聚相阻燃作用,以提高MH的阻燃效率.用XRD、红外、核磁等手段表征了BPF的化学结构.TGA研究表明BPF成炭性优异,750℃时残炭高达61%.阻燃PA6体系中,BPF与MH有显著的协效作用,材料能通过UL94-1.6 mm V0级别.BPF的阻燃增效机理分析表明,BPF燃烧时生成的B2O3可在燃烧材料表面富集形成玻璃态的有效阻隔层,使材料自熄.此外,BPF能显著提高材料加工流动性,具有较好增塑、润滑作用.BPF不会恶化材料力学性能,阻燃材料综合性能优良.