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.

中文翻译：

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N,N'-二(2,3-二羟基-丙基)-1,4-萘二丙酰胺及其作为单线态氧释放分子的 1,4-内过氧化物的可扩展合成

我们报告了非离子和水溶性单线态氧 ( ¹ O ₂ ) 载体分子N , N '-双(2,3-二羟丙基)-1,4-萘二丙酰胺的极大改进、操作简单且可扩展的三步合成-1,4-内过氧化物 (DHPNO ₂ )。从 1,4-二溴萘开始，开发的序列包括 (1) 无配体的 Pd 催化与丙烯酸甲酯的双 Heck 反应，(2) Pd/C 催化的氢化，以及 (3) 通过简单的甲酯氨解形成酰胺使用 3-amino-1,2-propanediol 得到N , N'-双(2,3-二羟丙基)-1,4-萘二丙酰胺 (DHPN)，总产率为 70%（三个步骤）。通过在 4°C 下对 DHPN 进行敏化光氧化获得的相应内过氧化物 DHPNO ₂在 D ₂ O 中的溶液（可在 -20°C 下储存）是一种有价值的研究工具，可以控制单线态氧 ( ¹ O ₂ ) 在生理温度下的水性生物系统中。