积雪草酸衍生物的合成及抗肿瘤活性研究

以天然产物积雪草酸为起始原料,对其C-2、C-3、C-23位羟基、C-11位氢、C-28位羧基进行结构改造,合成了13个新的积雪草酸衍生物,其结构经MS及1H NMR等确证。采用MTT法,选用高表达人癌细胞(He La、Hep G2和BGC-823)对它们进行初步的体外抗肿瘤活性研究,结果表明,所测化合物对He La、Hep G2和BGC-823肿瘤细胞的抑制活性均明显强于积雪草酸,其中化合物I4和II4对He La、Hep G2和BGC-823细胞表现出很强的抑制活性,明显高于已上市药物吉非替尼,值得进一步研究。     

Synthesis and anti-tumor activity of all-trans retinoic acid derivatives

A series of retinoate and retinamide derivatives were designed,synthesized,and their anti-tumor activities were investigated in NB4 by MTT and flow cytometry assays(FCM).All compounds showed cytotoxicity,especially compounds 1a and 1d exhibited a higher cytotoxicity than other derivatives and all-trans retinoic acid(ATRA).Furthermore,compound 1d could induce NB4 cell lines differentiation efficiently.     

Synthesis of 4-halotetrahydropyrans from allylsilanes and carbonyl compounds in the presence of lewis acids

An unexpected behavior of the reaction of allylsilanes and carbonylcompounds allowed the stereospecific preparation of differently substituted 4-halotetrahydropyrans with an “all cis” configuration.     

Synthesis, resolution, and aldol reactions of a planar-chiral Lewis acid complex

The synthesis and resolution of a new planar-chiral Lewis acid complex is described. The compound is applied to asymmetric Mukaiyama aldol reactions, leading to the formation of the desired product with good stereoselectivity. The sense of stereoselection is as predicted by the design, which exploits the ability of the Lewis acid to simultaneously serve as a sigma and a pi acceptor. Mechanistic observations are consistent with rate-determining formation of an aldehyde-Lewis acid complex, followed by rapid nucleophilic addition.     

Optimizing the matching between the acid and the base of cooperative catalysis to inhibit dehydration in the aldol condensation

A series of acid-base bifunctional catalysts were prepared, and high yields and excellent selectivity in the aldol condensation were achieved through adjustment of the matching between the acid and the base. The results indicated that proper matching between the acid and the base can both efficiently activate the substrate through cooperative activation and inhibit dehydration without diminishing the yield.     

氮杂岩白菜素衍生物的合成及其初步抗肿瘤活性

岩白菜素因其广泛的生理活性而备受关注。本文通过Mannich和Mitsunobu反应,合成了8个氮杂岩白菜素衍生物,其结构经1H NMR、13C NMR及质谱确证。采用MTT法初步测试了目标化合物体外抗肿瘤活性,结果表明,化合物3c和3d对细胞株A549均表现出优于岩白菜素的抑制活性(IC50分别为3.74μmol/L和5.05μmol/L),可做进一步研究。     

Polysiloxanol condensation and disproportionation in the presence of a superacid

Kinetics studies of the condensation of model hydroxyl-terminated oligosiloxanes, pentamethyldisiloxane-1-ol (MDH) and heptamethyltrisiloxane-1-ol (MD₂H), catalysed by protic complex of tetrakis(pentafluorophenyl)borate in the toluene solution were performed. The dominating reaction was condensation, which was accompanied by disproportionation of oligosiloxanols. Water released in the condensation forms separate dispersed phase, but the phase separation and the presence of water does not affect the rate of the polycondensation. Both processes, condensation and disproportionation, show analogous kinetic laws being first order in silanol and half order in catalyst. They exhibit also similar values of activation parameters. The kinetics are explained by the formation of a reactive protic complex of silanol with borate being in fast preequilibrium with an unreactive complex including two borate molecules and the silanol molecules. The equilibrium lies to the side of the unreactive borate complex.     

A kinetic and mechanistic study of the amino acid catalyzed aldol condensation of acetaldehyde in aqueous and salt solutions

The amino acid catalyzed aldol condensation is of great interest in organic synthesis and natural environments such as atmospheric particles. However, kinetic and mechanistic information on these reactions is limited. In this work the kinetics of the aldol condensation of acetaldehyde in water and aqueous salt solutions (NaCl, CaCl2, Na2SO4, MgSO4) catalyzed by five amino acids (glycine, alanine, serine, arginine, and proline) at room temperature (295 +/- 2 K) has been studied. Monitoring the formation of three products, crotonaldehyde, 2,4-hexadienal, and 2,4,6-octatrienal, by UV-vis absorption over 200-1100 nm revealed two distinct kinetic regimes: at low amino acid concentrations (in all cases, below 0.1 M), the overall reaction was first-order with respect to acetaldehyde and kinetically limited by the formation of the enamine intermediate. At larger amino acid concentrations (at least 0.3 M), the kinetics was second order and controlled by the C-C bond-forming step. The first-order rate constants increased linearly with amino acid concentration consistent with the enamine formation. Inorganic salts further accelerated the enamine formation according to their pKb plausibly by facilitating the iminium or enamine formation. The rate constant of the C-C bond-forming step varied with the square of amino acid concentration suggesting the involvement of two amino acid molecules. Thus, the reaction proceeded via a Mannich pathway. However, the contribution of an aldol pathway, first-order in amino acid, could not be excluded. Our results show that the rate constant for the self-condensation of acetaldehyde in aqueous atmospheric aerosols (up to 10 mM of amino acids) is identical to that in sulfuric acid 10-15 M (kI approximately 10-7-10-6 s-1) clearly illustrating the potential importance of amino acid catalysis in natural environments. This work also demonstrates that under usual laboratory conditions and in natural environments aldol condensation is likely to be kinetically controlled by the enamine formation. Notably, kinetic investigations of the C-C bond-forming addition step would only be possible with high concentrations of amino acids.     

Palladium-catalyzed carbonylation of chlorobenzene in the presence of lewis acids

Carbonylation of chlorobenzene to 4-chlorobenzophenone and/or benzoyl chloride may be catalyzed by PdCl₂ in the presence of Lewis acids MCl₃ (M=Al, Ga). Such a C−Cl bond carbonylation with a phosphine-free catalyst was previosly unknown.     

Bromination of pyridine in the presence of some lewis acids

The bromination of pyridine in the form of complexes with some Lewis acids and in the presence of catalytic amounts of the latter was studied. It is shown that bromination takes place readily at 100 °C in the presence of catalysts such as AlCl₃, ZnCl₂, CuCl₂, SbCl₃, InCl₃, TeCl₄, and HgCl₂. The principal bromination products are 3-bromopyridine and 3,5-dibromopyridine. The problem of the possibility of so-called back-bonding in the case of elements of the higher periods (particularly In, Te, and Sb) is discussed.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1236–1239, September, 1981.     

Bromination of quinoline in the presence of some lewis acids

Data on the bromination of quinoline in acetic anhydride and in the presence of salts of p and d elements are presented. High catalytic activity of the investigated salts, particularly the salts of p elements, was demonstrated. An unexpected orientation of the bromination of quinoline in 94% sulfuric acid in the presence of copper sulfate was discovered.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 548–550, April, 1985.     

Synthesis and anti-tumor activity evaluation of novel podophyllotoxin derivatives

In order to investigate the effects on the cytotoxicity of indole-3-oxalylamino podophyllotoxin analogs, seven novel podophyllotoxin derivatives were synthesized.The compounds were tested against Hela, K562 or K562/A02 cancer cells in vitro,four of which showed significant cytotoxicity.Among them 9a,9b and 9c were superior to the positive control VP-16.     

Organocatalytic asymmetric aldol reaction in the presence of water

Water was found to be a suitable solvent for the l-prolinethioamide catalysed aldol reaction of various cyclic ketones with aromatic aldehydes. Treatment of 4-nitrobenzaldehyde with as little as 1.2 equiv. of cyclohexanone in the presence of the protonated catalyst 1-TFA, afforded aldol products in high yields (up to 97%) with high diastereo- and enantioselectivity (up to >5 : 95 dr and 98% ee). The use of a high excess of ketone was avoided by conducting the aldol addition in the presence of water. Furthermore, different 'salting-out' and 'salting-in' salts were investigated and it was proven that the rate of acceleration and the stereochemical outcome of the reaction are affected by hydrophobic aggregation. Scope and limitation studies revealed that electron deficient aldehydes afforded aldol products with high stereoselectivity in the presence of 1-Cl(2)CHCO(2)H. It was shown that various cyclic ketones, under the conditions found, gave aldol products with fair yields, even if they are used in substoichiometric amounts (1.2 to 2.0 equiv.).     

Synthesis of new ionic-liquid-tagged organocatalysts and their application in stereoselective direct aldol reactions

New amino acid—1,2,3-triazolium conjugates were synthesized by establishing a 1,2,3-triazolium unit to the amino acid through Cu-catalyzed alkyne-azide cycloaddition and subsequent N-methylation. These products were applied as ionic-liquid-tagged organocatalysts in asymmetric direct aldol reactions. Remarkably, a lysine-derived conjugate performed better than proline derivatives. Evidence was found that IL-tagging improved the catalytic performance. Recycling of the organocatalyst was easily possible by extraction of products.     

Reactivity of some α-and α,γ - unsaturated silanes towards acetals in the presence of a lewis acid.

α-and α,γ-unsaturated silanes undergo titanium tetrachloride-induced alkylation of acetals.