Ethoxycarbonyl Methyl Research Articles

Benzoxazines as new human topoisomerase I inhibitors and potential poisons.

The numbers of topoisomerase I targeted drugs on the market are very limited although they are used clinically for treatment of solid tumors. Hence, studies about finding new chemical structures which specifically target topoisomerase I are still remarkable. In this present study, we tested previously synthesized 3,4-dihydro-2H-1,4-benzoxazin-3-one derivatives to reveal their human DNA topoisomerase I inhibitory potentials. We investigated inhibitory activities of 3,4-dihydro-2H-1,4-benzoxazin-3-one derivatives on human topoisomerase I by relaxation assay to clarify inhibition mechanisms of effective derivatives with EMSA and T4 DNA ligase based intercalation assay. With SAR study, it was tried to find out effective groups in the ring system. While 10 compounds showed catalytic inhibitory activity, 8 compounds were found to be potential topoisomerase poisons. 4 of them also exhibited both activities. 2-hydroxy-3,4-dihydro-2H-1,4-benzoxazin-3-one (BONC-001) was the most effective catalytic inhibitor (IC50:8.34mM) and ethyl 6-chloro-4-methyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-2-acetate (BONC-013) was the strongest potential poison (IC50:0.0006mM). BONC-013 was much more poisonous than camptothecin (IC50:0.034mM). Intercalation assay showed that BONC-013 was not an intercalator and BONC-001 most probably prevented enzyme-substrate binding in an unknown way. Another important result of this study was that OH group instead of ethoxycarbonylmethyl group at R position of benzoxazine ring was important for hTopo I catalytic inhibition while the attachment of a methyl group of R1 position at R2 position were play a role for increasing of its poisonous effect. As a result, we presented new DNA topoisomerase I inhibitors which might serve novel constructs for future anticancer agent designs. Graphical abstract.

Ethyl 2-(6-bromo-2-phenyl-1H-imidazo[4,5-b]pyridin-1-yl)acetate

In the title compound, C16H14BrN3O2, the fused-ring system is essentially planar, with the largest deviation from the mean plane being 0.0216 (15) Å for the substituted N atom of the five-membered ring, the plane of which makes dihedral angles of 28.50 (7) and 77.48 (7)° with the terminal phenyl ring and the ethoxycarbonylmethyl group mean planes, respectively. In the crystal, C—H...N hydrogen bonds link the molecules into inversion dimers. These combine with weak C—H...N contacts to stack the molecules into columns along theb-axis direction.

Functionalized Oxatriquinanes and Their Structural Equilibrium in Protic Solvent

We synthesized oxatriquinane hexafluorophosphate bearing an ethoxycarbonylmethyl group 7 or a 2-oxopropyl group 11. Both of these organic oxonium cation compounds were obtained as stable solids. However, (1)H-NMR analysis showed that oxatriquinane 7 was present as the oxonium cation in aprotic solvent CD₃CN, but was in rapid equilibrium with ring-opened bicyclic compound 8 in protic solvent CD₃OD. The oxatriquinane 11 also showed similar behavior in protic solvent. Phenyl-substituted oxatriquinanes 12 and 14 were also obtained as stable solids, and showed similar properties to 7 and 11.

1-Ethyl 2,2-dimethyl 3-(1,3-benzodioxol-5-yl)propane-1,2,2-tricarboxylate

The molecular structure of the title triester compound, C(17)H(20)O(8), consists of a benzodioxole fused-ring system, an ethoxycarbonylmethyl group and two methoxycarbonyl groups arranged around a tetrahedral carbon center. Unlike similar triesters, which are oils, the title compound crystallizes at room temperature as interdigitated bilayers of triester molecules, with short O...H contacts from the methylene H atoms of benzodioxole to the carbonyl O atom of the ethoxycarbonylmethyl group and to a ring O atom of the benzodioxole group of a neighboring molecule within the bilayer. The persistence of these short C-H...O interactions from the activated H atoms of the benzodioxole ring at both 100 and 300 K indicate that they help provide the stabilization necessary for crystallization from the oil.

Stereoselective Synthesis of a Novel Chiral Piperazine

- (2S,6S)-2,4,6-Tris(phenylmethyl)piperazine was prepared in 11 steps and 53% overall yield from S-phenylalanine. Key steps in the synthesis involved reductive amination to introduce an ethoxycarbonylmethyl group on to the secondary nitrogen of the product and selective alkylation to introduce a benzyl group with complete diastereoselectivity.

Synthesis of pyrrolidines and tetrahydro-1H-azepines from 4-aryl-1-benzoyl(ethoxycarbonyl)methyl-1-methyl-1,2,3,6-tetrahydropyridinium halides

4-Aryl-1,2,3,6-tetrahydropyridinium quaternary salts which have a benzoylmethyl or ethoxycarbonylmethyl group on atom N-1 generate N-ylides when heated in the presence of NaH and they can rearrange in situ with contraction or expansion of the six-membered heterocycle to give substituted pyrrolidines (as a result of a [2,3]-sigmatropic rearrangement) or 1H-tetrahydroazepine derivatives (via Stevens rearrangement). The presence of an aryl substituent at position C-4 in the tetrahydropyridine ring allows to avoid the formation of elimination products and changes the direction of the reaction towards the preparation of the tetrahydroazepines.

Ethyl (1-methyl-3-phenyl-5-thioxo-4,5-dihydro-1H-1,2,4-triazol-4-yl)acetate

All interatomic distances in the title compound, C13H15N3O2S, are normal. The 1,2,4-triazole ring is planar and is inclined at 46.50 (6)° to the phenyl ring. The ethoxycarbonylmethyl group is also close to being planar and is inclined at 87.54 (9)° to the 1,2,4-triazole ring. The crystal was an inversion twin with a twin ratio 0.88 (3):0.12 (3).

ChemInform Abstract: Convenient Synthesis of Disubstituted Cyclic Ethers. Syntheses of (‐)‐cis‐Rose Oxide and (cis‐6‐Methyltetrahydropyran‐2‐yl)acetic Acid.

AbstractThe cyclic lactones (I), (IV), or (VII) are coupled with the ketene acetal (II) in the presence of triethylsilane and Lewis acid catalyst systems containing antimony(V) to produce the cyclic ethers (III), (V), or (VIII) which bear the ethoxycarbonyl methyl group at position 2. The ratio of cis/trans‐isomers is determined by the substitution pattern.

ChemInform Abstract: Synthesis and Reductive Desulfurization of Crown Ethers Containing Thiophene Subunit.

Crown ethers containing 3,4-thiophenediyl and 3,4-thiophenediylbis(methylene) subunits as a ring constituent were prepared starting from 2,5-bis(ethoxycarbonyl)-3,4-thiophenediol and 2,5-dichloro-3,4-bis(chloromethyl)thiophene, respectively. A Raney nickel desulfurization of the thiophene-containing crown ethers afforded crown ethers having two adjacent side chains, such as a methyl or ethoxycarbonylmethyl group. The extraction ability of these crown ethers towards alkali metal cations was also examined by the solvent extraction method.

Synthesis and Reductive Desulfurization of Crown Ethers Containing Thiophene Subunit

Abstract Crown ethers containing 3,4-thiophenediyl and 3,4-thiophenediylbis(methylene) subunits as a ring constituent were prepared starting from 2,5-bis(ethoxycarbonyl)-3,4-thiophenediol and 2,5-dichloro-3,4-bis(chloromethyl)thiophene, respectively. A Raney nickel desulfurization of the thiophene-containing crown ethers afforded crown ethers having two adjacent side chains, such as a methyl or ethoxycarbonylmethyl group. The extraction ability of these crown ethers towards alkali metal cations was also examined by the solvent extraction method.

Total Synthesis of 13β-Allylgonanes. III

The improved method for synthesizing gonanes having the allyl group at C-13 was examined. Potassium salt of 2-ethoxycarbonylmethylcyclopentane-1, 3-dione (I) was choosen as a starting material and the ethoxycarbonylmethyl group was converted into the allyl group after the steroid skeleton was formed.

Stability of the silicon-carbon bond in alkoxy(alkyl)silanes. Containing ether or ester groupings toward nucleophilic and electrophilic reagents

1. The following compounds were synthesized for the first time: dibutoxy(methoxymethyl)methylsilane, triethoxy(methoxymethyl)silane, [acetyl(ethoxycarbonyl)methyl]diethoxymethylsilane, and (bisethoxycarbonylmethyl) diethoxyethylsilane. 2. It was shown that, in the hydrolysis of diethoxy(ethoxycarbonylmethyl)ethylsilane and diethoxy(ethoxycarbonylmethyl)phenylsilane in alkaline and acid media, elimination of the ethoxycarbonylmethyl group occurs. 3. It was shown that, in the hydrolysis of diethoxy(ethoxymethyl)rnethylsilane, hydrolysis of siliconattached ethoxy groups is accompanied by partial elimination of the ethoxymethyl group, the extent of the elimination being greater in an acid medium than in an alkaline medium. 4. In the hydrolysis of diacetoxy(acetoxymethyl)methylsilane, rupture of the silicon-carbon link in the grouping Si- CH2OCOCH3 does not occur to any appreciable extent either in alkaline or in acid media. 5. Alkaline hydrolysis of [acetyl(ethoxycarbonyl)methyl]diethoxymethylsilane does not result in rupture of the link between silicon and the carbon of the ester grouping.Such rupture does occur in acid hydrolysis.