Anthracyclinone glycosidation

Also 2 -halo-3 -hydroxy derivatives of various anthracyclinones show a high activity against P 388 mouse leukemia in certain in-vivo tests. A compound like 98 has been prepared in the 2-deoxy-2-iodo-a-L-ma no-series by Horton et al. [59, 60] starting from di-O-acetyl-L-rhamnal (28). Similarly, Thiem et al. have also successfully prepared the tetracenomycinone-C glycoside 99 [61]. From 4-0-acetyl-3-0-(p-methoxy)-benzyl-L-fucal (102) the glycoside derivatives 103 and 104 in the talo-series were obtained. 

Acton, E M, Ryan, K J, Tracy, M, Synthetic approach to anthracyclinone C-glycosides, Tetrahedron Lett., 25, 5743-5746, 1984. 

Many of these transformations are also carried out on the analogous anthracyclinones—the aglycone portions of these molecules. Others occur on the glycosides, such as the N-acetylation of the daunosamine moiety of daunomycin and daunomycinol by Bacillus subtilis var, mycoides (36). 

Anthracyclines constitute another complex and bigger family of antibiotics. They mostly occur as glycosides of the anthracyclinones (aglycone residue). They act by intercalation with the DNA in both normal and neoplastic cells. 

For the isolation and purification of anthracyclines and anthracyclinones, the culture broth is sometimes acidified or basidified, depending on the pJCa value, followed by filtration and extraction with organic solvents. The lipophihc anthracyclinones are mostly concentrated in the mycelium and must be extracted with acetone and acetone/dichloromethane mixtures. The more polar members of the glycosides are present mainly in the culture filtrate and can be recovered by repeated extraction with ethyl acetate or -more conveniently - by adsorption resins Hke XAD-7 or Diaion HP-20. To isolate residual parts from the mycehum, acetone under addition of acetic acid may be required. Under these conditions, however, some anthracyclines are aheady cleaved, and this may be the reason that only very few glycosides with more than four sugar units in a chain have been described in the hteratme. 

In contrast to the anthracyclinones [21,22], the more polar glycosides usually do not give reliable mass spectra on electron impact ionization (EI-MS). In cases such as cinerubin A (23), where aromatization can take place easily, the sugar residues are split off completely, and the bisanhydro-aglycones are formed. In the spectrum of 23, the signal of ]-pyrromycinone (24) is detected (m/z = 392). 

The anthracyclines are pigmented glycosidic antibiotics produced by different strains of Streptomyces. The first of these naturally occurring compounds, P-rhodomycine (la), was isolated by Brockmann and Bauer in 1950 from Streptomycespurpurescens [1]. In the 1950s other rhodomycins were obtained and subsequently their structures were elucidated, mainly by Brockmann [2] and Ollis [3]. The aglycone moieties of these compounds were named anthracyclinones and belong to the various types of rhodomycinones. Examples of representative structures are shown in Fig. 1. 

In our laboratory we have developed a novel approach to the synthesis of an enantiopure AB segment of the anthracyclinones based on a new type of chiral substrate, enone 131 [131,132]. Di-O-acetyl-L-rhamnal (129), obtained from L-rhamnose, was converted into benzyl glycoside 130 [133] by the Perrier procediue [134], Hydrolysis and oxidation of the C-4 (carbohydrate numbering) hydroxyl group in 130 gave enone 131 in 67% overall yield (Scheme 27). It is worthy of note that uloside 131 is also readily available from a non-sugar chiral pool. Enzymatic resolution of racemic l-(2-furyl)ethanol yielded the (S)-enantiomer 138 in 98% ee [135]. This was transformed in two steps, by known procedures, into ulose 139 (Scheme 28) [136,137] from which uloside 131 was readily obtained. 

A new cytotoxic antibiotic cytorhodin X from a Streptomyces strain has been shown to be an unusual anthracyclinone 9a-glycoside 6. Another new anthracycline antibiotic, dutomycin, also obtained from a Streptomyces strain, contains a disaccharide component 7 including the branched chain sugar L-axenose. ... 

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