Daunomycin 14-hydroxy

Figure 5-23 Stereoscopic drawing showing a molecule of daunomycin (Fig. 5-22) intercalated between two base pairs in a molecule of double-helical DNA, d(CGTACG). Nitrogen and oxygen atoms are shown as dots. From Quigley et al.220 Both daunomycin and adriamycin (doxorubicin 14-hydroxy-daunomycin) are important but seriously toxic anticancer drugs.

Genes coding for NDP-hexose synthetases and NDP-hexose 4,6-dehydratases have been found in the clusters of the antibiotics granaticin (10) [122], streptomycin (24) [72], hydroxy-streptomycin [72], amphotericin [103], tylosin (46) [143], daunomycin (29) [144], lincomycin [145], landomycin A (12) and urda-... 

A 26-year-old woman with a diffuse large B cell lymphoma received CHOP (cyclophosphamide, hydroxy-daunomycin, Oncovin, and prednisone), ritnximab, and radiotherapy (14). She developed a transfnsion-dependent anemia. Bone marrow biopsy confirmed pure red cell aplasia and parvovirus infection. She had no antibodies to parvovirus, suggesting that she never had a previous exposure. Intravenous immunoglobulin resulted in a reticulocytosis and recovery of her hemoglobin. 

Patients with localized aggressive lymphomas can be cured with several cycles of cyclophosphamide, hydroxy-daunomycin (doxorubicin), vincristine (Oncovin), and prednisone (CHOP) chemotherapy and involved-field irradiation. Patients with bulky stage II, stage III, or stage IV aggressive lymphomas can be cured of their disease with CHOP chemotherapy. The addition of rituximab to CHOP (R-CHOP) is used by many centers in place of CHOP. 

The utility of oxaziridines in asymmetric a-hydroxylation also extends to reactions with achiral enolates. This has been made possible by the discovery that certain chiral A -sulfonyl oxaziridines can react with enolates to afford a-hydroxy carbon compounds in excellent yield and enantioselectivity. An application of a highly selective sulfonyloxaziridine derived from camphor to the synthesis of daunomycin is shown in Scheme 8.23. Attack of the oxaziridine presumably occurs such that the enolate ester avoids nonbonded interactions with the exo methoxy group on the bicyclic ring system (cf. Schemes 8.23c and d). This is a very useful reaction of wide scope, and can be carried out on both stabilized enolates derived from keto esters (shown) and simple ketone enolates [99]. 

Doxorubicin, BAN, INN, USAN 14-Hydroxy daunomycin. Adriacin. Adriblastin. Caelyx. Dox. Doxil. Farmiblastina. FI 106. K1039. KW125. NSC 123127 [23214-92-8]... 

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