posted on 2021-12-09, 17:06authored byMichael Gemki, Ömer Taspinar, Andreas Adler, Axel G. Griesbeck, Dirk Gründemann, Hans-Günther Schmalz
We report a greatly
improved, operationally simple, and scalable
three-step synthesis of the nonionic and water-soluble singlet oxygen
(1O2) carrier molecule N,N′-bis(2,3-dihydroxypropyl)-1,4-naphthalenedipropanamide-1,4-endoperoxide
(DHPNO2). Starting from 1,4-dibromonaphthalene, the developed
sequence involves (1) a ligand-free Pd-catalyzed double Heck reaction
with methyl acrylate, (2) Pd/C-catalyzed hydrogenation, and (3) amide
formation by simple methyl ester aminolysis using 3-amino-1,2-propanediol
to give N,N′-bis(2,3-dihydroxypropyl)-1,4-naphthalenedipropanamide
(DHPN) in 70% overall yield (three steps). A solution of the corresponding
endoperoxide DHPNO2 in D2O (storable at −20
°C), obtained by sensitized photo-oxidation of DHPN at 4 °C,
is a valuable research tool allowing a controlled release of singlet oxygen (1O2) in aqueous biological systems at physiological temperatures.