RESUMEN
Eribulin mesylate, one of the most synthetically challenging drugs to date, possesses 19 stereocentres in its structure and ascertaining the absolute stereochemistry at every stage of the 64-stage synthesis is crucial. In our quest to synthesize eribulin, we identified two critical building blocks of this molecule, namely 3,4:6,7-di-O-cyclohexylidene-D-glycero-α-L-talo-heptopyranose methanol monosolvate, C19H30O7·CH3OH, and (2R,3R,4R,5S)-5-allyl-2-[(S)-2,3-dihydroxypropyl]-4-[(phenylsulfonyl)methyl]tetrahydrofuran-3-ol, C17H24O6S, for which two-dimensional NMR (2D-NMR) data were not sufficient to prove the absolute configuration. To ensure structural integrity, single-crystal X-ray diffraction data were obtained to confirm the structures. This information provides useful insights into the structural framework of the large eribulin mesylate molecule.
Asunto(s)
Compuestos Alílicos/química , Compuestos Alílicos/clasificación , Antineoplásicos/química , Ciclohexenos/química , Furanos/química , Furanos/síntesis química , Cetonas/síntesis química , Monosacáridos/química , Antineoplásicos/farmacología , Cristalografía por Rayos X , Furanos/farmacología , Enlace de Hidrógeno , Cetonas/química , Cetonas/farmacología , Espectroscopía de Resonancia Magnética , Difracción de Rayos XRESUMEN
Low molecular weight polyurethanes with sites for metal complexation were synthesized. The -SO(2) and the -COOH groups were incorporated into the polyurethane chain by the reactions of tri-functional monomers, 4,4'-bis(hydroxyphenyl)sulfone and 4,4'-bis(hydroxyphenyl) valeric acid with hexa-methylene di-isocyanate (HMDI) and 2,4 toluene di-isocyanate (TDI), respectively. The reaction was monitored from the disappearance of the -OH group and results show that the -NCO groups of the isocyanate reacted with the -OH group preferentially when compared to the other reactive groups. The pristine tri-functional monomers themselves formed stable complexes with the metals and so were chosen to be incorporated into the polyurethane chain. These polymers were characterized by IR and NMR spectroscopy. The free -SO(2) and the -COOH groups were used for metal complexation using non-toxic metals like zinc and silver. The anti-bacterial studies conducted on the six polymers in film form showed interesting results as elaborated in the paper.