新型7-O-(芳基氨基甲酸酯)-布雷菲德菌素A的合成及其抗肿瘤活性

芳胺与三光气反应制得芳基异氰酸酯(2a~2n);2a~2n分别对布雷菲德菌素A(3)的7-羟基进行结构修饰,合成了14个新型布雷菲德菌素A氨基甲酸酯类衍生物——7-O-(芳基氨基甲酸酯)-布雷菲德菌素A(4a~4n),其结构经1H NMR,13C NMR和ESI-HR-MS表征。初步的抗肿瘤活性测定结果表明,4i~4k均丧失抑制食管癌细胞株TE-1活性。分子对接研究揭示,引入3后,4的分子空间位阻增大,导致不能与靶位结合,致使抗肿瘤活性丧失。     

Mechanistic aspects on molecular structure formation of polymeric networks from diisocyanates with amidine compounds

Polymeric networks are produced by step‐growth polyaddition and co‐polyaddition reactions of 1‐ethylimidazoline in combination with various diisocyanates. Five aromatic, two aliphatic diisocyanates and a polyurethane prepolymer are used as particular reactant in N,N‐dimethylformamide as solvent at room temperature. Obviously, 1‐ethylimidazoline can serve as trifunctional monomer, which enables a crosslinking reaction with diisocyanates. Molecular structure elements of the polymeric networks were studied by solid state 13C‐NMR spectroscopy revealing that detailed molecular structure formations are determined whether aromatic or aliphatic diisocyanates are used. Quantum chemical calculations were used as supporting method to elucidate the complex reaction cascades. Hence, it can be shown that beside 3:1 stoichiometric structures 2:1 based structures are formed as well. These structures are observed as kinetically controlled products only when aromatic diisocyanate monomers are used. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018 , 56, 977–985     

Polyurea microcapsules from isocyanatoethyl methacrylate copolymers

The synthesis of two types of isocyanate side chain containing copolymers, poly(methyl methacrylate‐co‐isocyanatoethyl methacrylate) (P(MMA‐co‐IEM)) and poly(benzyl methacrylate‐co‐isocyanatoethyl methacrylate) (P(BnMA‐co‐IEM)), which were synthesized by Cu(0)‐mediated radical polymerization, is reported. Polymerization proceeded to high conversion giving polymers of relatively narrow molar mass distributions. The incorporation of the bulky aromatic groups in the latter copolymer rendered it sufficiently stable toward hydrolysis and enabled the isolation of the product and its characterization by ¹H and ¹³C NMR, and FTIR spectroscopy and SEC. Both P(MMA‐co‐IEM) and P(BnMA‐co‐IEM) were functionalized with dibutylamine, octylamine, and (R)‐(+)‐α‐methylbenzyl‐amine, which further proved the successful incorporation of the isocyanate groups. Furthermore, P(BnMA‐co‐IEM) was used for the fabrication of liquid core microcapsules via oil‐in‐water interfacial polymerization with diethylenetriamine as crosslinker. The particles obtained were in the size range of 10–90 µm in diameter independent of the composition of copolymer. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 2698–2705     

Synthesis of poly(isopropenylphenoxy propylene carbonate) and its facile side‐chain functionalization into hydroxy‐polyurethanes

4‐Isopropenyl phenol ( 4‐IPP ) is a versatile dual functional intermediate that can be prepared readily from bisphenol‐A ( BPA ). Through etherification with epichlorohydrin to the phenolic group of 4‐IPP , it can be converted into 4‐isopropenyl phenyl glycidyl ether ( IPGE ). On further reaction with carbon dioxide in the presence of tetra‐n‐butyl ammonium bromide ( TBAB ) as the catalyst, IPGE was transformed into 4‐isopropenylphenoxy propylene carbonate ( IPPC ) in 90% yield. Cationic polymerization of IPPC with strong acid such as trifluoromethanesulfonic acid or boron trifluoride diethyl etherate as the catalyst at ?40 °C gave a linear poly(isopropenylphenoxy propylene carbonate), poly( IPPC ), with multicyclic carbonate groups substituted uniformly at the side‐chains of the polymer. The cyclic carbonate groups of poly( IPPC ) were further reacted with different aliphatic amines and diamines resulting in formation of polymers with hydroxy‐polyurethane on side‐chains. Syntheses, characterizations of poly( IPPC ) and its conversion into hydroxy‐polyurethane crosslinked polymers were presented. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 802–808     

4-氧-3-氮杂-三环[5.3.1.02,5]十一烷-9-甲酸甲酯的合成及晶体结构

以2-金刚烷酮为起始原料,通过烯烃与氯磺酰异氰酸酯的[2+2]环加成等5步反应合成了新型双环β-内酰胺类化合物5.采用1H NMR,IR和MS等手段对所得化合物的结构进行了表征.此外,还通过将化合物5酰化并采用X射线单晶衍射分析方法进一步测定了化合物5的空间立体结构.结果表明,烯烃3与氯磺酰异氰酸酯的[2+2]环加成反...     

Lanthanide-catalyzed cyclocarbonylation and cyclothiocarbonylation: a facile synthesis of benzannulated 1,3-diheteroatom five- and six-membered heterocycles

<正>NMR spectra were recorded in CDCl3 or DMSO-d6 on a Bruker Avance 400 operating at 400 MHz with TMS as internal standard. 1H-benzo[d]imidazol-2(3H)-one(3aa) [1]: 1H NMR(400 MHz, DMSO-d6) δ 10.5(s, 2 H, NH), 6.90(s, 4H)(aromatic CH). 13 C NMR(400 MHz, DMSO-d6) δ 155.7, 130.1, 120.9, 108.9. NH HN O3 aa 1-(2-Aminophenyl)-3-phenylurea(3aa′) [2]: 1H NMR(400 MHz, DMSO-d6) δ 8.75(s, 1H), 7.71(s, 1H)(CONH), 7.44(d, J = 8.0 Hz, 2H), 7.33(d, J = 7.8 Hz, 1H), 7.26(t, J = 7.7 Hz, 2H), 6.94(t, J = 7.4 Hz, 1H), 6.84(t, J = 7.4 Hz, 1H), 6.74(d, J = 7.8 Hz, 1H), 6.57(t, J = 7.4 Hz, 1H)(aromatic CH), 4.78(s, 2H)(NH2). 13 C NMR(400 MHz, DMSO-d6) δ 153.6, 141.4, 140.6, 129.2, 125.2, 124.8, 124.2,121.9, 118.4, 117.3, 116.4.     

Evaluation of hydrophobic‐interaction chromatography resins for purification of antibody‐drug conjugates using a mimetic model with adjustable hydrophobicity

Antibody drug conjugates are cytotoxic pharmaceuticals, designed to destroy malignant cells. A cytotoxic molecule is attached to an antibody that binds specific to a cancer‐cell surface. Given the high toxicity of the drugs, strict safety standards have to be kept. For this reason, an antibody drug conjugates model was developed with fluorescein 5‐isothiocyanate as the nontoxic payload surrogate. Due to the similar hydrophobicity, this model is used to establish a suitable purification process and characterization method for antibody drug conjugates. Because of the pH dependent solubility of fluorescein, the hydrophobicity of conjugates can be modulated by the pH value. Based on the complex heterogeneity and hydrophobicity of the conjugates a chromatographic purification is challenging. Hydrophobic interaction chromatography is used for analytical as well as for preparative separation. Because of the increased hydrophobicity of the conjugates compared to native antibody, hydrophobic interaction chromatography often suffer from resolution and recovery problems. Conjugates were separated differing on the number of payloads attached to the antibody. For this matter, the drug–antibody ratio is determined and used as a quantitative term. The conjugates are purified at high recoveries and resolution by step gradients using suitable resins, allowing the separation of the target drug–antibody ratio.     

Spectroscopic Properties,Conformation and Structure of Difluorothiophosphoryl Isocyanate in the Gaseous and Solid Phase

Difluorothiophosphoryl isocyanate, F₂P(S)NCO was characterized with UV/vis, NMR, IR (gas and Ar-matrix), and Raman (liquid) spectroscopy. Its molecular structure was also established by means of gas electron diffraction (GED) and single crystal X-ray diffraction (XRD) in the gas phase and solid state, respectively. The analysis of the spectroscopic data and molecular structures is complemented by extensive quantum-chemical calculations. Theoretically, the C_s symmetric syn-conformer is predicted to be the most stable conformation. Rotation about the P−N bond requires about 9 kJ mol⁻¹ and the predicted existence of an anti-conformer is dependent on the quantum-chemical method used. This syn-orientation of the isocyanate group is the only one found in the gas phase and contained likewise in the crystal. The overall molecular structure is very similar in gas and solid, despite in the solid state the molecules arrange through intramolecular O⋅⋅⋅F contacts into layers, which are further interconnected by S⋅⋅⋅N, S⋅⋅⋅C and C⋅⋅⋅F contacts. Additionally, the photodecomposition of F₂P(S)NCO to form CO, F₂P(S)N, and F₂PNCO is observed in the solid Ar-matrix.     

Lutetium‐Methanediide‐Alkyl Complexes: Synthesis and Chemistry

The first four‐coordinate methanediide/alkyl lutetium complex (BODDI)Lu₂(CH₂SiMe₃)₂(μ₂‐CHSiMe₃)(THF)₂ (BODDI=ArNC(Me)CHCOCHC(Me)NAr, Ar=2,6‐iPr₂C₆H₃) ( 1 ) was synthesized by a thermolysis methodology through α‐H abstraction from a Lu–CH₂SiMe₃ group. Complex 1 reacted with equimolar 2,6‐iPrC₆H₃NH₂ and Ph₂C?O to give the corresponding lutetium bridging imido and oxo complexes (BODDI)Lu₂(CH₂SiMe₃)₂(μ₂‐N‐2,6‐iPr₂C₆H₃)(THF)₂ ( 2 ) and (BODDI)Lu₂(CH₂SiMe₃)₂(μ₂‐O)(THF)₂ ( 3 ). Treatment of 3 with Ph₂C?O (4 equiv) caused a rare insertion of Lu–μ₂‐O bond into the C?O group to afford a diphenylmethyl diolate complex 4 . Reaction of 1 with PhN=C?O (2 equiv) led to the migration of SiMe₃ to the amido nitrogen atom to give complex (BODDI)Lu₂(CH₂SiMe₃)₂‐μ‐{PhNC(O)CHC(O)NPh(SiMe₃)‐κ³N,O,O}(THF) ( 5 ). Reaction of 1 with tBuN?C formed an unprecedented product (BODDI)Lu₂(CH₂SiMe₃){μ₂‐[η²:η²‐tBuNC(=CH₂)SiMe₂CHC?NtBu‐κ¹N]}(tBuN?C)₂ ( 6 ) through a cascade reaction of N?C bond insertion, sequential cyclometalative γ‐(sp³)‐H activation, C?C bond formation, and rearrangement of the newly formed carbene intermediate. The possible mechanistic pathways between 1 , PhN?C?O, and tBuN?C were elucidated by DFT calculations.