Abstract:
:10-Acetyl-7,8-dihydroxyxantho[2,3-f]tetralin is obtained by photo-Fries rearrangement of an acylated and double ketal protected tetralin followed by sodium thiocresylate catalyzed rearrangement of the resulting benzoyltetralin. Introduction of the 10-hydroxy function with base, triethyl phosphite, and molecular oxygen affords six products. These include the desired epimeric 10-acetyl-7,8,10-trihydroxyxantho[2,3-f]tetralins in addition to products resulting from novel valence tautomerism and cycloreversion reactions in the oxidation reaction. Glycosidic coupling to the fully functionalized cis-8,10-dihydroxy epimer of the aglycon to protected chlorodaunosamine by a modified Koenigs-Knorr method proceeded satisfactorily. By contrast the epimeric trans-8,10-dihydroxy compound failed to undergo coupling under these conditions. This is attributed to facile competing intramolecular hemiketal formation in the latter case. The new angular glycosides are very resistant to electrochemical reduction and display very low (3-10%) augmentation of hepatic microsomal oxygen consumption relative to doxorubicin. The observed, albeit low, cytotoxicity against leukemia L1210 in cell culture provides an additional example where the presence of the quinone moiety in the parent anthracyclines, which is implicated in the clinical cardiotoxicity, may not be necessary for the expression of anticancer properties.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Lown JW,Sondhi SM,Plambeck JAdoi
10.1021/jm00161a018subject
Has Abstractpub_date
1986-11-01 00:00:00pages
2235-41issue
11eissn
0022-2623issn
1520-4804journal_volume
29pub_type
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