Tuyet Anh Dang Thi

Synthesis of 1-alkyl-2-(trifluoromethyl)azetidines and their regiospecific ring opening toward diverse α-(trifluoromethyl)amines via intermediate azetidinium salts.

A convenient approach toward nonactivated 1-alkyl-2-(trifluoromethyl)azetidines as a new class of constrained azaheterocycles was developed starting from ethyl 4,4,4-trifluoroacetoacetate via imination, hydride reduction, chlorination, and base-induced ring closure. Furthermore, the reactivity profile of these 2-CF(3)-azetidines was assessed by means of quaternization and subsequent regiospecific ring opening at C4 of the azetidinium intermediates by oxygen, nitrogen, carbon, sulfur, and halogen nucleophiles, pointing to a clear difference in reactivity compared to azetidines bearing other types of electron-withdrawing groups at C2.

Nucleophile-directed selective transformation of cis-1-tosyl-2-tosyloxymethyl-3-(trifluoromethyl)aziridine into aziridines, azetidines, and benzo-fused dithianes, oxathianes, dioxanes, and (thio)morpholines.

A five-step procedure for the synthesis of cis-1-tosyl-2-tosyloxymethyl-3-(trifluoromethyl)aziridine was developed, starting from 1-ethoxy-2,2,2-trifluoroethanol, involving imination, aziridination, ester reduction, hydrogenation, and N-,O-ditosylation steps. Further synthetic elaborations revealed a remarkable difference in the reactivity of cis-1-tosyl-2-tosyloxymethyl-3-(trifluoromethyl)aziridine with respect to aromatic sulfur and oxygen nucleophiles, thus enabling the selective deployment of this versatile substrate as a building block for the synthesis of functionalized aziridines, azetidines, and benzo-fused dithianes, oxathianes, dioxanes, and (thio)morpholines.

Synthesis and cytotoxic evaluation of novel ester-triazole-linked triterpenoid–AZT conjugates

Betulinic acid and analogous naturally occurring triterpenoid acids were transformed into the corresponding propargyl esters and subsequently deployed as substrates for a click chemistry-mediated coupling with azidothymidine (AZT) en route to novel 1,2,3-triazole-tethered triterpenoid-AZT conjugates. Twelve new hybrids were thus prepared and assessed in terms of their cytotoxic activity, revealing an interesting anticancer activity of five triterpenoid-AZT hybrids on KB and Hep-G2 tumor cell lines.

Synthesis and anticancer properties of new (dihydro)pyranonaphthoquinones and their epoxy analogs

1,4-Dihydroxy-2-naphthoic acid was used as a substrate for a straightforward five-step synthesis of 3-substituted 1H-benzo[g]isochromene-5,10-diones, with a Michael addition of N-acylmethylpyridinium ylides across 2-hydroxymethyl-1,4-naphthoquinone and a subsequent acid-mediated dehydratation of intermediate hemiacetals as the key steps. The obtained benzo[g]isochromene-5,10-diones were subsequently deployed for further synthetic elaboration to produce new 3,4-dihydrobenzo[g]isochromene-5,10-diones and (3,4-dihydro-)4a,10a-epoxybenzo[g]isochromene-5,10-diones. All compounds were screened for their cytotoxic and antimicrobial effects, revealing an interesting cytotoxic activity of 1H-benzo[g]isochromene-5,10-diones against different cancer cell lines.

Synthesis of new simplified hemiasterlin derivatives with α,β-unsaturated carbonyl moiety.

In this Letter, we report a convenient and efficient method for the synthesis of new simplified derivatives of hemiasterlin in which the α,α-dimethylbenzylic moiety A is replaced by α,β-unsaturated aryl groups as Michael acceptor. Most of these derivatives have a strong cytotoxic activity on three human tumor cell lines (KB, Hep-G2 and MCF7). Analogs 17b and 17f showed a high cytotoxicity against KB and Hep-G2 cancer cell lines comparable to paclitaxel and ellipticine.

Synthesis of new bioisosteric hemiasterlin analogues with extremely high cytotoxicity

In this Letter, the synthesis and the evaluation of the cytotoxicity of new hemiasterlin analogues were reported. The indole moiety was replaced respectively by benzofurane, naphthalene and 4-bromobenzene groups. Most of these derivatives possess strong cytotoxic activity on two human tumour cell lines (KB and Hep-G2), and some analogues showed comparable cytotoxic activity to that observed for paclitaxel and ellipticine, against KB and Hep-G2 cancer cell lines.

Design, synthesis and evaluation of novel hybrids between 4-anilinoquinazolines and substituted triazoles as potent cytotoxic agents

In this research several series of novel dioxygenated ring fused 4-anilinoquinazolines (10a-d) and 4-anilinoquinazoline-substituted triazole hybrid compounds (11-14) have been designed and synthesized. Their biological significance was highlighted by evaluating in vitro for anticancer activities, wherein several compounds displayed excellent activity specifically against three human cancer cell lines (KB, epidermoid carcinoma; HepG2, hepatoma carcinoma; SK-Lu-1, non-small lung cancer). Especially, compound 13a exhibited up to 100-fold higher cytotoxicity in comparison with erlotinib. Docking the most cytotoxic compounds (11d, 13a, 13b, and 14c) into the ATP binding site of different EGFR tyrosine kinase domains was perfomed to predict the analogous binding mode of these compounds to the EGFR targets.

Crystal structure of 22,24,25-trimethyl-8,11,14-trioxa-25-aza­tetra­cyclo­[19.3.1.02,7.015,20]penta­cosa-2,4,6,15(20),16,18-hexaen-23-one

Macrocyclic 22,24,25-trimethyl-8,11,14-trioxa-25-azatetracyclo[19.3.1.02,7.015,20]pentacosa-2,4,6,15 (20),16,18-hexaen-23-one obtained by a Petrenko–Kritchenko condensation of 1,5-bis(2-formylphenoxy)-3-oxapentane, pentan-3-one and methylammonium acetate has been studied by X-ray structural analysis.