<unk>  is a 4'-epi-isomer of doxorubicin and a derivative of daunorubicin. As an anthracycline antibiotic it belongs to several chemical classes such as: aminoglycosides, tetracene quinones, p-quinones, primary alpha-hydroxy ketone and tertiary alpha-hydroxy ketones. Due to numerous ionisable groups, it has multiple pka (pKa1 = 9.17 (phenol); pKa2 = 9.93 (amine); pKa3 = 12.67 (hydroxyl)) and is soluble in a variety of solvents (DMSO 125 mg/mL; Ethanol 120 mg/mL; In water, 93 mg/L at 25 °C (est)). It has a melting point of 344.53 and a boiling point of 810.3±65.0 °C at 760 mmHg. Its shelf life (def. as the time it takes to degrade 10% from the initial concentration) has been documented as at least 14 and 180 days at 25 °C and 4 °C, respectively in a 0.9% sodium chloride solution in polypropylene syringes. Synthesis There are multiple ways of synthesizing<unk>  depending on which starting material is used as a precursor. Daunorubicin One pathway starts from Daunorubicin, a common byproduct found in fermentation, since it is relatively easily available and already structurally similar to the product (only requiring minor alterations). Firstly, the amine group is protected using trifluoroacetic acid to stop it from further reactions. Next the hydroxyl group needs to be changed from an equatorial position to an axial, this is achieved by firstly oxidizing an intermediate sulfoxy salt to a keto group (losing the optical center) followed by a stereo-specific reduction using sodium borohydride to give the hydroxide group in the axial position. Secondly, the focus shifts to carbon number 13 where it is necessary to add a hydroxide group which is achieved by bromination followed by a reaction with an alkali salt of formic acid and water to give the final product. There is an older variant of this pathway which involves first splitting the Daunorubicin, into daunomycin one and daunosamine methyl ether, using methanol. Analogous reactions are performed to get the two hydroxyl groups onto their positions and the rings are then recombined and the protecting groups released. The drawbacks are more chemicals are used and daunomycin one and daunosamine need to be separated first. 13-daunorubicinol The second pathway startsfrom 13-daunorubicinol (hydroxyl group on carbon 13 instead of Daunorubicin’s keto group). Firstly, the amine group is protected using trifluoroacetic acid then both the hydroxyl groups at positions 4 and 13 are oxidized simultaneously to keto groups again using DMSO, but a different alkylating agent. The reduction to alcohol is performed with a derivative of a borohydride of an alkali metal with formula MHBL3, where M=Li, Na, K; L=AlkO, AlkCOO, ArCOO. The subsequent halogenation is performed with a complex halogenating agent where an H or a chain of up to 4 carbons is combined with Cl, I or Br. The final hydrolysis is analogous to the one in the first pathway.
Epirubicin
Valrubicin
Ifosfamide
Vincristine
Doxorubicin
Daunorubicin
Mitoxantrone
Etoposide