MRA-CN, NSC 357704, ADR-489
5,12-萘二苯二酮,10-[[3-(3-氰基-4-吗啡酰)-2,3,6-三氧化氧-a-L-lyxo-六甲苯基]氧]-7,8,9,10-四氢-6,8,11-三羟基-8-(2-羟基乙酰)-1-甲氧基,(8S,10S)-Chemical Name: 3'-Deamino-3'-(3-cyanomorpholin-4-yl)doxorubicin hydrate
CAS No. 88254-07-3, 89196-07-6 (3(R)-CN isomer), 89196-08-7 (3(S)-CN isomer)
项目整合开发状态: Preclinical
项目研究机构: Pfizer (Originator), SRI (Originator)
合成路线:MRA-CN is a byproduct of the synthesis of 3'-deamino-3'-(4-morpholinyl)doxorubicin (III) by the reductive alkylation of doxorubicin (I) with 2,2'-oxybisacetaldehyde (II) and NaBH3CN (I).An iminium intermediate in this process evidenly undergoes nucleophilic attack by cyanide ion present in the reaction mixture,in competition with the normal attack by hydride.Unlike the expected morpholino derivative (III) (and most anthracyclines),MRA-CN is nonbasic.It remains in the organic layer (e.g.,chloroform) when the morpholino derivative is extracted with dilute aqueous acid.MRA-CN is then recovered from the organic layer and purified by chromatography on silica gel using gradient elution with dichloromethane-methanol.Yields range from 15% to 40%.MRA-CN does not form an HCl salt.
📌 参考资料/链接：
参考文献标题:MRA-CN
文献作者:Acton,E.M.
参考来源:Drugs Fut 1985,10(9),750
📄 详细内容
合成路线:MRA-CN is a byproduct of the synthesis of 3'-deamino-3'-(4-morpholinyl)doxorubicin (III) by the reductive alkylation of doxorubicin (I) with 2,2'-oxybisacetaldehyde (II) and NaBH3CN (I).An iminium intermediate in this process evidenly undergoes nucleophilic attack by cyanide ion present in the reaction mixture,in competition with the normal attack by hydride.Unlike the expected morpholino derivative (III) (and most anthracyclines),MRA-CN is nonbasic.It remains in the organic layer (e.g.,chloroform) when the morpholino derivative is extracted with dilute aqueous acid.MRA-CN is then recovered from the organic layer and purified by chromatography on silica gel using gradient elution with dichloromethane-methanol.Yields range from 15% to 40%.MRA-CN does not form an HCl salt.
参考文献标题:Intensely potent morpholinyl anthracyclines
文献作者:Acton,E.M.; et al.
参考来源:J Med Chem 1984,27(5),638-45
产品链接: CAS No. 88254-07-3››