3-Rhodomycinone

These studies were undertaken in connection with a possible route to unsym-metrically functionalized anthraquinones for intermediates to rhodomycinones. 

Hydroxymethylation of anthraquinones (Marschalk reaction). Krohn1 has reviewed this reaction, particularly for the synthesis of anthracyclinones. It is particularly useful for preparation of optically active rhodomycinones by use of chiral aldehydes (166 references). 

Marschalk alkylation (8, 456). The intramolecular Marschalk alkylation is useful in syntheses of the tetracyclic ring system of the cytostatic anthracycline antibiotics. A bimolecular version of the reaction involves condensation of 1 with glyoxylic acid and alcoholic KOH. The product of this reaction is reduced and esterified to afford 2 in 33% overall yield. Less than 5% of the isomeric product 3 is obtained. 9-Deoxy-e-rhodomycinone 4 is available from 2 in two steps (details not provided). ... 

Oxidation of the lithium enolate of 1-tetralone 23 to (—)-2-hydroxy-l-tetralone 24, the AB ring synthon of the antitumour antibiotic rhodomycinones, with (+)-18 (X = OMe, Y = H, equation 10) resulted in much better enantiomeric excess values (ee >94%) than hydroxylation with other oxaridines. ... 

Nevertheless, a few biosynthetic studies have shown that glycosyl transfer can occur much earlier, sometimes well before construction of the aglycon moiety is complete. In the perhaps best-known example, the biosynthesis of daunomycin (= daunorubicin, 29) and adriamycin (= doxorubicin, 30), glycosyl transfer of daunosamine is postulated to occur either at the aklavinone (38) stage [86], as in the biosynthesis of aclacinomycin A 37 (see above), or after 11-hydroxylation to -rhodomycinone [87], i. e., six to seven biosynthetic steps prior to completion of adriamycin formation (30, Scheme 17) [88]. 

Easily prepared from glycols, enones have been investigated as dienophiles. They react with butadiene under Lewis acid catalysis to form chiral cyclohexenes used in the synthesis of compactin analogs [353]. Levoglucosenone has been used in a Diels-Alder reaction with acetoxy-butadiene to construct a part of the indole alkaloid reserpine [354], and in synthetic studies toward tetrodotoxin [355]. Analogs of the anthracycline rhodomycinone have been similarly prepared [356]. [4 + 2]-Cycloaddition of the same enone with silyloxydiene allowed the creation of the fused ring system present in actinobolin [357]. 

Dyong, I, Hagedorn, H-W, Thiem, J, Diastereoselective aufbau eines rhodomycinone-modells aus D-glucose, Liebigs Ann. Chem., 551-563, 1986. 

Rhodomycin A, C H N-jO. 3 -rhodomycin II, Dec on mild acidic hydrolysis into 1 mole 3 -rhodomycinone and 2 moles rhodosamine Brockmann, Spohler, Naturwiss. 48,... 

Dioxolanone 58c, when reduced to lactol 61, is a masked 1,4-dialdehyde (64) equivalent. The aldehyde, which is freed by ozonolysis and acidic hydrolysis, undergoes a Marschalk reaction with leucoquinizarine (65) to give rhodomycinone 66 in 45% yield [22] (Scheme 9). 

Trihydroxylated anthracycHne and anthracycUnones can be divided into four majors classes, based on the position of the OH groups 1,4,6-trihydroxyan-thracyclinones belong in majority to the pyrromycinone type the 1,4,11- and the 4,6,11-trihydroxyquinones are usually summarized as rhodomycinones. 

Two aglycones were reported in the small group of 1,4,11-trihydroxylated anthracyclines, Q 2-rhodomycinone (35a) and 5-rhodomycinone (Fo 214). Glycosides such as alldimycin-A (35b), B (35c), C (35d), and violamycin-B2 (35e) isolated from Streptomyces violaceus A262, as well as 1-hydroxy-serirubicin (35f) isolated from Streptomyces cyaneus MG344-hF49 all have the Q 2-rhodomycinone aglycone 35a. 

Anthracyclines glycosylated at the 4-position are very rarely mentioned in the literature, and 4-0-(/l-D-glucopyranosyl)-fi-rhodomycinone (39a) isolated from a mutant of Actinomadura roseoviolacea was the first one of this series. It exhibited no antibacterial or cytotoxic activity [66]. However, its glucuronic acid derivative histomodulin (39b), isolated from Streptomyces ruber JCM3131, was reported as an up-regulator of MHC class-I molecules in B16/BL6 cells [67]. 

In the group of trihydroxyanthraq clines, four of the five natural free 10-carboxyHc acids are found one of them is carborubicin (39c). Semi-synthetically, the free acids can be easily decarboxylated and simultaneously hydroxylated under inversion of configuration by UV irradiation in the presence of iodine [68]. In a typical experiment, carborubicin (39c) was irradiated at 350 nm in acetone/water at pH 5.2 for 1 h to deliver the rhodomycinone-glycoside 10-epz-oxaunomycin (D-788-7, 39d, a-configuration at C-10) in a yield of 34%. In ammonia/acetone, decarboxylation occms imder retention, and oxaunomycin (39e) is formed [69]. 

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