合成路线1

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.

合成路线2

A fermentation broth of RMN-134-13 was filtered, adjusted at pH 3.4 and centrifuged. The liquid was passed through Diajon HP-20 and eluted with acetone-0.01 M HCl-KCl buffer. The luate was combined with the precipitate of the preceding centrifugation to which acetone and 28% aq. ammonia was added. After stirring for 3-4 h at 20 C the solution was adjusted at pH 7.2 with H2SO4, concentrated and extracted with CH3OH-CHCl3. After a cumbersome purification by HPLC, 13 deoxo-10-hydroxycarminomycin (oxaunomycin) (I) was obtained. Finally, the preceding compound was treated with diglycol dialdehyde (II) and sodium cyano-borohydride in CHCl3.

合成路线3