TY - JOUR
T1 - Synthesis of steroidal dendrimers modified by 'click' chemistry with PAMAM dendrons as unimolecular micelles
AU - Soto-Castro, Delia
AU - Magaña-Vergara, Nancy E.
AU - Farfán, Norberto
AU - Santillan, Rosa
N1 - Funding Information:
The authors thank CONACyT and PAPIIT IN 214513 for financial support, Ma. T. Cortez for NMR spectra and Cuéllar Rivera Geiser for HRMS. A postdoctoral fellowship to D. Soto from CONACyT are gratefully acknowledged. N. Magaña thanks to ICyt for a Ph. D fellowship.
PY - 2014/1/29
Y1 - 2014/1/29
N2 - Novel Fréchet-PAMAM hybrid dendrimers linked by triazole units as unimolecular micelles with a hydrophobic core surrounded by a hydrophilic shell were prepared. The dendritic cores with 3 and 6 alkyne terminal groups were synthesized from 1,3,5-tribromomethyl-benzene (tBrMeB), in one case by direct coupling with 17α-ethynylestradiol (EE); in the second one the tBrMeB was reacted with bis(hydroxymethyl) phenol followed by chlorination of the hydroxyl groups and subsequent coupling to EE. With this strategy, the core can be grown by further substitutions of bis(hydroxymethyl) phenol over the halogenated terminals as Fréchet dendrimer. The hydrophilic shells used were PAMAM type dendrons of 0.5 and 1.5 generations with azide as focal point and tert-butyl ester as end groups. The unimolecular micelles were obtained by cycloaddition between an azide in the selected dendron and the alkyne terminal in the hydrophobic core to obtain a 1,4-disubstituted 1,2,3-triazole. Once the coupling was achieved, the tert-butyl ester groups were hydrolyzed in trifluoroacetic acid and the corresponding dendrimers with carboxylic acid as end groups were completely soluble in phosphate buffer solutions of pH 7.0, 7.4, and 8.0. All hybrid dendrimers were characterized by High Resolution Mass Spectrometry, 1H and 13C NMR, and FTIR.
AB - Novel Fréchet-PAMAM hybrid dendrimers linked by triazole units as unimolecular micelles with a hydrophobic core surrounded by a hydrophilic shell were prepared. The dendritic cores with 3 and 6 alkyne terminal groups were synthesized from 1,3,5-tribromomethyl-benzene (tBrMeB), in one case by direct coupling with 17α-ethynylestradiol (EE); in the second one the tBrMeB was reacted with bis(hydroxymethyl) phenol followed by chlorination of the hydroxyl groups and subsequent coupling to EE. With this strategy, the core can be grown by further substitutions of bis(hydroxymethyl) phenol over the halogenated terminals as Fréchet dendrimer. The hydrophilic shells used were PAMAM type dendrons of 0.5 and 1.5 generations with azide as focal point and tert-butyl ester as end groups. The unimolecular micelles were obtained by cycloaddition between an azide in the selected dendron and the alkyne terminal in the hydrophobic core to obtain a 1,4-disubstituted 1,2,3-triazole. Once the coupling was achieved, the tert-butyl ester groups were hydrolyzed in trifluoroacetic acid and the corresponding dendrimers with carboxylic acid as end groups were completely soluble in phosphate buffer solutions of pH 7.0, 7.4, and 8.0. All hybrid dendrimers were characterized by High Resolution Mass Spectrometry, 1H and 13C NMR, and FTIR.
KW - Click chemistry
KW - Ethynylestradiol
KW - Triazole
KW - Unimolecular micelles
UR - http://www.scopus.com/inward/record.url?scp=84892821933&partnerID=8YFLogxK
U2 - 10.1016/j.tetlet.2013.12.066
DO - 10.1016/j.tetlet.2013.12.066
M3 - Artículo
SN - 0040-4039
VL - 55
SP - 1014
EP - 1019
JO - Tetrahedron Letters
JF - Tetrahedron Letters
IS - 5
ER -