Anthracycline derivatives

Vogel185 used 3-aza-6,8-dioxabicyclo[3.2.1]octane based chiral dienophiles to prepare anthracyclines and anthracycline derivatives. 

Figure 8.23 Anthracycline derivatives generated by gene inactivation or by combining gene inactivation and gene expression.

S.G. Vitols, M. Masquelier and C.O. Peterson, Selective uptake of a toxic lipophilic anthracycline derivative by the low-density lipoprotein receptor pathway in cultured fibroblasts, J. Med. Chem. 28 (1985) 451-454. 

O. Chassany, S. Urien, P. Claudepierre, G. Bastian, and J. P. Tillement, Binding of anthracycline derivatives to human serum lipoproteins, Anticancer Res. 14 2353-2355 (1994). 

Some variants of the above methods have been successfully utilized in total syntheses. For example, anomeric vinyl stannanes were found useful for coupling with suitable vinyl or aromatic iodides. This allowed the total synthesis of the anthracycline derivative vineomycinone B2 using palladium... 

Umezawa H, Takeuchi T, Hamada M, Naganawa H, Sawa T, Uchida T, Imoto M (1986) Anthracycline derivatives and their use as medicaments. EP Patent 167935 (Chem... 

AretzW, BerscheidHG, Huber G, Fehlhaber HW, Kraemer HP, SedlacekHH, Ganguli BN, Sood RS, Gandhi J, Reddy GC (1985) Microbiological production of anthracycline derivatives, and their cytostatic use. DE Patent 3 323 025 (Chem Abstr 102 147547)... 

These esters (p-trifluoromethyl- and p-fluoro-benzoate) are prodrugs of DOXO [52] and have been used in cellular uptake studies. Despite the low cytotoxicity with respect to the parent anthracyclines, these esters may find apphcation for slow release. In fact, this possibility has already been explored. Some 14-(co, CO, -trifluoromethyl)-alkyl-anthracycline derivatives 57 (Fig. 7) with satisfactory carcinostatic properties have also been patented [53]. 

Furthermore, ME2303 was the most effective anthracycline derivative in mice, bearing established liver metastases of Lewis lung carcinoma. This compound was investigated in pharmacokinetic studies the tissue distribution of... 

Cycloadditions between naphthoquinones and a 1,2-dimethylidenecyclo-hexane derivative have been used to prepare pentacyclic compounds, e.g. (196), " while a related cycloaddition between isobenzofurans and benzoquinone monoacetal derivatives occurs regioselectively leading to anthracycline derivatives such as (197). ... 

The silyl groups at the newly formed benzene ring were cleaved by the action of acetyl chloride in anhydrous methanol and tetrabutylammonium fluoride to yield 34 and 35, respectively. A Tamao-Fleming-like oxidation to furnish the respective phenol derivatives did not take place, probably due to the sp -hybridized carbon of the arene moiety. To install the anthraquinone moiety by oxidation of the benzylic positions, it was necessary to reprotect the alcohol functionalities. After tert-butyldimethylsilyl protection of the hydroxyl moieties to afford 36, an iron(III)-catalyzed benzylic oxidation proceeded smoothly with yields up to 70%. Finally, hydrolysis with hydrochloric acid of the protecting groups generated the desired anthracycline derivatives 38 based on a carbohydrate skeleton [21,22] (Scheme 8.8). 

SCHEME 8.8 Silyl ether coupling, domino carbopalladation reaction, and deiivatization to anthracycline derivatives. 

Phipps, R,K, Blunt, J,W., Cole, A.L.J., and Mumo, M.H.G. (2004) Anthracycline derivatives from a marine-derived New Zealand Streptomycete. ARKIVOC, 94-100,... 

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