Enantioselective synthesis of the AB-ring system of the antitumor antibiotic tetrazomine

The synthesis of the 1,2,3,4-tetrahydroisoquinoline moiety of tetrazomine was accomplished in 18 steps and in 3% overall yield from commercially available o-anisaldehyde. The reaction sequence utilizes a Sharpless asymmetric dihydroxylation to install the stereocenter and an intramolecular Friedel--Crafts hydroxyalkylation with an N-protected 2-oxo-acetamide to close the heterocyclic ring.     

Novel efficient synthesis of an enantiomeric pair of tricycloillicinone

The title synthesis was achieved starting with 3-ethoxy-2-cyclohexenone by a method featuring Davis’ asymmetric hydroxylation and Pauson-Khand reaction as the key steps.     

Efficient synthesis and antitumor activity of novel 14-fluoroanthracyclines

The title compounds, (+)-14-fluoro-4-demethoxy- and (+)-14-fluorodaunorubicin, were synthesized from (−)-7-deoxy-4-demethoxy- and (−)-7-deoxydaunomycinone, respectively, by featuring the novel fluorination reaction in which tetrabuthylammonium fluoride is employed in the presence of a half equiv of p-toluenesulfonic acid as a key step. These novel anthracyclines were found to exhibit significant inhibitory activity against P388 murine leukemia in vitro and in vivo.     

Ferrocene‐modified thiopyrimidines: synthesis,enantiomeric resolution,antitumor activity

Ferrocenylalkyl thiopyrimidines ( 6a–d to 9a–d ) were prepared via the reaction of the α‐(hydroxy)alkyl ferrocenes, FcCHR(OH) ( 1a–d ; Fc = ferrocenyl; R = H, Me, Et, Ph), with 2‐thiopyrimidines ( 2 – 5 ) in acetone at room temperature in the presence of TFA, yielding 50–95%. The resulting enantiomers were resolved using HPLC on modified cellulose as chiral selector. The antitumor activities of S‐ferrocenylethyl 2‐thiopyrimidine ( 6b ) against two murine solid tumor models, carcinoma 755 (Ca755) and Lewis lung carcinoma (LLC) were evaluated in vivo. The strong antitumor effect of compound 6b on Ca755 and LLC was demonstrated. The index of tumor growth inhibition on Ca755 equaled 95% in comparison with control. Copyright © 2010 John Wiley & Sons, Ltd.     

Efficient synthesis and biological activity of enantiomeric pairs of thiolactomycin and its 3-demethyl derivative

The title total synthesis was achieved by employing deconjugative asymmetric α-sulfenylation of the chiral 3-(α,β,γ,δ-unsaturated acyl)oxazolidin-2-one with a 3,3-dimethoxypropyl methanethiosulfonate as a key step. From the biological activity assay carried out using the title compounds, it appeared evident that in vitro antibacterial and mammalian type I FAS inhibitory activity can be cleanly separated by changing not only the substituent at the C₃-position but also the absolute configuration at the C₅-position, and that unnatural (S)-(−)-3-demethylthiolactomycin and its congeners might be usable as selective mammalian type I FAS inhibitors.     

A racemic synthesis of an AB-ring system of hexacyclinic acid

[structure: see text] An AB-ring system of the polyketide natural product hexacyclinic acid has been synthesized in racemic form. The key steps were an intramolecular Diels-Alder cyclization of an ester tethered 1,3-nonadiene-8-yne, which generated the B-ring, and a samarium diiodide mediated reductive annulation, which was used to form the A-ring.     

Efficient enantiomeric synthesis of pyrrolidine and piperidine alkaloids from tobacco

An enantiomeric synthesis of six piperidine and pyrrolidine alkaloids, (S)-nornicotine 1, (S)-nicotine 2, (S)-anatabine 3, (S)-N-methylanatabine 4, (S)-anabasine 5, and (S)-N-methylanabasine 6, known as natural products in tobacco, was established from a common chiral homoallylic (S)-3-(1-azido-but-3-enyl)-pyridine 15. An intramolecular hydroboration-cycloalkylation of the homoallylic azide intermediate 15 served as the key step in the pyrrolidine ring formation. A ring closing metathesis reaction (RCM) of a diethylenic amine intermediate (S)-allyl-(1-pyridin-3-yl-but-3-enyl)-carbamic acid benzyl ester 20 served as the key step in the piperidine ring formation. From the commercially available 3-pyridinecarboxaldehyde 13, a short and convenient enantiomeric synthesis of tobacco alkaloids is described: (S)-nornicotine 1 (5 steps, with an overall yield of 70%), (S)-nicotine 2 (6 steps, 65%), (S)-anatabine 3 (8 steps, 30%), (S)-N-methylanatabine 4 (8 steps, 25%), (S)-anabasine 5 (8 steps, 35%), and (S)-N-methylanabasine 6 (8 steps, 25%).     

Efficient synthesis of enantiomeric pairs of thiolactomycin and its 3-demethyl derivative

Starting with commercially available tiglic aldehyde, the title synthesis was achieved by employing deconjugative asymmetric α-sulfenylation of the chiral 3-(α,β,γ,δ-unsaturated acyl)-2-oxazolidinone with a methanethiosulfonate as a key step.     

Arvanil的绿色合成及其抗肿瘤活性

采用微波辐射、硅胶负载和催化合成辣椒素类似物Aranvil,在高产率地得到Aranvil的同时,建立了一种微波辅助、硅胶负载和催化合成辣椒素及其类似物的绿色合成新方法.该方法具有无需使用腐蚀性或毒性大的羧酸活化试剂、无溶剂、操作简单、反应时间短、收率高、环境友好等优点.并采用MTT法考察了Aranvil对脑胶质瘤C6细胞和人肝癌Huh7细胞的体外增殖抑制作用,结果显示Aranvil具有较好的抗肿瘤活性.     

Chemical modification of an antitumor alkaloid camptothecin: synthesis and antitumor activity of 7-C-substituted camptothecins.

A radical substitution reaction of 20(S)-camptothecin (1) with methanol furnished 7-hydroxymethylcamptothecin (2). Reaction of 1 with primary alcohols higher than methanol gave 7-alkylcamptothecins (4), of which alkyl groups were one carbon less than the alcohols used and also 7-hydroxyalkylcamptothecins (5). For the preparation of 7-alkylcamptothecin (4), aldehydes were used as a radical source and several alkylated derivatives were synthesized. 7-Acyloxymethyl derivatives (6), 7-carbaldehyde (7), iminomethyl derivatives (10), acid (11), esters (12) and amides (13) were synthesized starting from 2. 7-Ethyl- (4b) and 7-propylcamptothecin (4c), acyloxymethyl compounds 6a, 6c and ethyl ester (12b) exhibited higher antitumor activity than 1 against L1210 in mice.     

Opposite stereochemical courses for enzyme-mediated alkene reductions of an enantiomeric substrate pair

Rat NADP-dependent leukotriene B4 12-hydroxydehydrogenase (Ltb4dh) catalyzes olefin reductions for some activated alkenes at the expense of NADPH in the absence of a flavin cofactor. Unlike flavoprotein alkene reductases, where net trans-addition of hydrogen has been consistently observed, Ltb4dh reduced both enantiomers of perillaldehyde to the same cis-product. To uncover the reason for this unexpected result, the stereochemical courses of perillaldehyde reductions by Ltb4dh were determined by deuterium labeling followed by (2)H NMR analysis. These data showed unequivocally that Ltb4dh mediated net trans-addition of hydrogen to (R)-perillaldehyde but followed the opposite stereochemical course (net syn-addition) for (S)-perillaldehyde. To the best of our knowledge, such divergent stereochemical pathways for a single enzyme have not previously been reported.     

Efficient microwave-assisted synthesis of new sulfonylbenzimidazole-4,7-diones: heterocyclic quinones with potential antitumor activity

New benzimidazoloquinones substituted at 2-position by a sulfonyl group have been synthesized via a final microwave assisted step using 2-chloromethyl-1,5,6-trimethylbenzimidazole-4,7-dione 7 as starting material.     

Efficient and mild cyclization procedures for the synthesis of novel 2-amino-4H-pyran derivatives with potential antitumor activity

A series of novel 2-amino-4H-pyran derivatives have been synthesized via a three-component reaction of α,β-unsaturated ketone derivatives, malononitrile, aldehydes in excellent yields, using DBU as a catalyst and ethanol as a cheap, safe, and environmentally benign solvent under mild conditions. Their antitumor activity was evaluated in three human tumor cell lines, including human colon cancer （HCT116）, human cervical cancer （Hela）. and non-small cell lung cancer （H1975）.     

Synthesis of sesbanimide: An approach for the synthesis of ring C

A simple method for the construction of C-ring of sesbanimide utilizing the condensation of 2-benzyloxymethylcrotyl bromide with an aldehyde in the presence of zinc as the key step is described.     

Optical evodiamine derivatives:Asymmetric synthesis and antitumor activity

Evodiamine and its derivatives have an asymmetric center at the C13 b position.Herein,isomers of evodiamine derivatives 2 and 3 were obtained by straightforward asymmetric total synthesis.Their inhibitory activities toward topoisomerases I and II and their cytotoxicities in cancer cell lines were evaluated.All the four isomers exhibited good to excellent antitumor potency and the(S)-isomers were generally more active than the(R)-isomers.The binding modes of(S)-2 with topoisomerases I and II were also clarified by molecular docking.     

新型N-甲基吲哚类衍生物的设计、合成及抗肿瘤活性研究

本文以吲哚骨架为起点,设计合成了5个含吲哚骨架的新型有机小分子(4a-4e),通过NMR,IR和MS对目标化合物进行了结构表征.采用MTS法测试了目标化合物对SMMC-7721,Hela,MCF-7和HepG2癌细胞的体外抗肿瘤活性.结果表明,部分化合物选择性地作用于一种细胞,显示出较强的抑制肿瘤细胞增殖的活性,值得进一步研究.     

Efficient synthesis and antioxidant activity of coelenterazine analogues

A convenient and highly convergent method for the synthesis of new imidazo[1,2-a]pyridine-based coelenterazine analogues is reported. The imidazo[1,2-a]pyridine core was constructed through a condensation between 2-aminopyridine analogues and arylglyoxals. Additionally, a new approach to the synthesis of benzylglyoxals was introduced. The imidazo[1,2-a]pyridines display moderate antioxidant activities at a low micromolar level in 2,2-diphenyl-1-picrylhydrazyl (DPPH).     

Efficient one-pot synthesis of anti HIV and antitumor compounds: harman and substituted harmans

Anti HIV and antitumor compounds, harman and substituted harmans have been synthesized using electrocyclization reactions as key steps. A one-pot reaction sequence was used to furnish these compounds in good overall yield.