Regiospecific synthesis of 11-desoxyanthracycline antibiotics starting with aloe-emodin
✍ Scribed by J. Alexander; D.L. Flynn; L.A. Mitscher; T. Veysoglu
- Publisher
- Elsevier Science
- Year
- 1981
- Tongue
- French
- Weight
- 207 KB
- Volume
- 22
- Category
- Article
- ISSN
- 0040-4039
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✦ Synopsis
The regiospecific synthesis of an established ll-desoxyanthracycline synthon ($) from aloe-emodin (3a) is described. The contemporary search for analogues of the anthracycline antitumor antibiotics daunomycin' and doxorubicin2 is intense. Particularly desired is the development of analogues retaining antitumor activity but with reduced cardiotoxicity. 3 Toward this end, we consider the ll-desoxyanthracyclines as an attractive area for synthetic exploration. Recently, the isolation and antitumor activities of aclacinomycin A (h),4 and ll-desoxydaunomycin (a).5 as well as ll-desoxydoxorubicin ($)5 have been reported. Although much synthetic effort has been directed toward daunomycinone, none of these procedures appear applicable to the regiospecific synthesis of lldesoxyanthracyclinones lb, &, or g. 637 839 Recent communications describing the synthesis of the ll-desoxydaunomycinone synthon 8& have prompted us to report our quite different approach. Our work is based upon the convenient availability of the naturally-occurring anthraquinone, alo;;emodin (3a)." g-Ally'lltion (C) and Claisen rearrangement (&) proceed from known ether & in 66 and 96% yields. Peracetylation ($, pyridine/Ac20; 98%) followed by hydroboration (BH3/THF; H202/NaOAc; 42%) gave the desired primary alcohol (5a). Oxidation (CrO,/H,SO,/Me,CO) and esterification/ethanolysis (EtOH/ cat. H2S04) completed elaboration of the lower side chain in the form of ester 2 (64% from k):