0000000000281731
AUTHOR
Antonio Espinosa
Antitumoural properties of benzannelated seven-membered 5-fluorouracil derivatives and related open analogues. Molecular markers for apoptosis and cell cycle dysregulation.
Attention is increasingly being focussed on the cell cycle and apoptosis as potential targets for therapeutic intervention in cancer. We prepared a series of bioisosteric benzannelated seven-membered 5-FU O,N-acetals to test them against the MCF-7 human breast cancer cell line. Benzo-fused seven-membered O,O-acetals or their acyclic analogues led to the expected 5-FU O,N-acetals (or aminals), in addition to six- and 14-membered aminal structures and acyclic compounds. All the cyclic aminals provoked a G0/G1-phase cell cycle arrest, whereas Ftorafur, a known prodrug of 5-FU, and 1-[2-(2-hydroxymethyl-4-nitrophenoxy)-1-methoxyethyl]-5-fluorouracil (11) induced an S-phase cell cycle arrest. Al…
Substituent effects on the reaction mode between 2-hydroxybenzyl alcohol derivatives and MEM chloride:synthesis and mechanistic aspects of seven-and ten-membered benzo-fused O,O-acetals
Abstract The synthesis of (RS)-2- or (RS)-3-methoxy-2,3-dihydro-5H-1,4-benzodioxepins and (RS)-5- or (RS)-3-methoxy-2,3,5,6-tetrahydro-8H-benzo-[1,4,7]-trioxecins has been developed. The mechanism of such a reaction via the boron trifluoride etherate-promoted transformation of 2-(methoxyethoxymethoxy)benzyloxyacetaldehyde dimethyl acetals or 2-(methoxyethoxymethoxymethyl)phenyloxyacetaldehyde dimethyl acetals has been proposed. Transannular versions of the reaction results in the facile ring contraction of 12-membered intermediates to the 10- and to 7-membered benzene-fused O,O-acetals. The characterization of the by-products strongly supports the mechanisms proposed.