Synthesis and radioiodination of some daunorubicin and doxorubicin derivatives

• Published in: Carbohydrate research 2005-01, Vol.340 (1), p.15-24
• Main Authors: Ghirmai, Senait, Mume, Eskender, Tolmachev, Vladimir, Sjöberg, Stefan
• Format: Article
• Language: English
• Subjects: 125I; Chemistry; Chloramine-T; Chromatography, Thin Layer; Daunorubicin; Daunorubicin - analogs & derivatives; Daunorubicin - chemical synthesis; Daunorubicin - chemistry; Doxorubicin; Doxorubicin - analogs & derivatives; Doxorubicin - chemical synthesis; Doxorubicin - chemistry; Iodine Radioisotopes - chemistry; Kemi; Molecular Structure; NATURAL SCIENCES; NATURVETENSKAP; Organic chemistry; Organisk kemi; Radioiodination
• ISSN: 0008-6215; 1873-426X; 1873-426X
• DOI: 10.1016/j.carres.2004.10.014

[Display omitted] Daunorubicin and doxorubicin are efficient agents for cancer treatment. Their clinical efficacy is, however, hampered by their indiscriminant toxicity. This problem may be circumvented by encapsulating the drugs in liposomes and selectively targeting the tumor cells using tumor targeting agents. Furthermore, the antitumor effect could be enhanced by attaching the Auger electron emitter, 125I, to daunorubicin and doxorubicin derivatives. In this context a number of ester, amide, and amine derivatives of daunorubicin and doxorubicin were synthesized. Benzoic acid ester derivatives of daunorubicin were synthesized by nucleophilic esterification of the 14-bromodaunorubicin with the potassium salt of the corresponding benzoic acid, resulting in good yields. Nicotinic acids and benzoic acids, activated with a succinimidyl group, were coupled to the amino group of daunorubicin to give the corresponding amide derivatives. Amine derivatives were obtained by the reductive amination of aromatic aldehydes with daunorubicin hydrochloride. The stannylated ester and amide derivatives were used as precursors for radioiodination. Radiolabeling with 125I was performed using chloramine-T as an oxidant. The optimized labeling resulted in high radiolabeling yields (85–95%) of the radioiodinated daunorubicin and doxorubicin derivatives. Radioiodination of the amines was conducted at the ortho position of the activated phenyl rings providing moderate radiochemical yields (55–75%).