Anthracyclinones isolation

Anthracyclinone synthesis. Wulf and Xu1 have reported a high-yield formal synthesis of 11-deoxydaunomycinone (5) in which the first step is a benzannelation of the chromium carbene 1 with the acetylene 2 to provide the naphthol 3, which is not isolated but treated with TFA to induce cleavage of the /-butyl ester and to... 

The tetrakis(methylidene)-7-oxabicyclo[2.2.1]heptane (527) offers an interesting route to linear poly-annulated ring systems, e.g. 4Klemethoxydaunomycinone (641), via a sequence of two Diels-Alder reactions (Scheme 124). Monoadduct (528) could be isolated and subjected to the [4 + 2] cycloaddition of benzyne. An alternative synthesis of anthracyclinone analogs starts with the Diels-Alder addition of 3-methoxybenzyne to a derivative of the bis-cisoid tetraene (527). ... 

Antkracyclinones. The use of latent quinone reagents such as 2-lithio-3,3,6,6-tetramethoxy-l,4-cyclohexadiene has been extended to a synthesis of an anthra-cyclinone. The starting material 1 was converted into the quinone bisketal 2 by anodic oxidation. The corresponding lithio compound was then condensed with dimethyl 3-methoxyphthalate (3). The reaction fortunately was stereoselective and resulted in 4 in satisfactory yield. The conversion of 4 to the anthracyclinone 5 was conducted in three steps without isolation of intermediates reductive hydrolysis to the hydroquinone, saponification, and finally cyclization with hydrogen fluoride. The overall yield of 5 from 3-bromo-2,5-dimethoxybenzalde-hyde, the precursor of 1, was 8%. ... 

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. 

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. 

Reductive hydrolysis with Raney nickel [112] yielded aldehyde 93, which was reacted with leucoquinizarine (86) with aeration to give the epimeric mixture 94. Reduction of the benzyUc hydroxy group in 94 with sodium dithionite followed by hydrolysis of the isopropyhdene protection and subsequent periodate oxidation furnished aldehyde 95. Sequential treatment of 95 with sodiiun dithionite in 7% NaOH and air oxidation provided a 4 1 C-7 epimeric mixture of anthracyclinones. The major diastereoisomer, 4-demethoxyfeudomycinone C (96) was isolated by column chromatography. 

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