Methylation and hydroxylation studies on aloe-emodin

Abstract

20 J. Org. Chem. 8.10. Found C, 68.65; H, 8.39.4@-(2,5@,6,6-Tetramet hyl-2-cyclohexenyl)-3( E)-buten-&one (2a,. The ketone 18a (35 mg, 0.09 mmol) in dry THF (3 mL) was added to MeONa (30 mg, 0.57 mmol) dissolved in t-BuOH (6 mL) at 5 OC under N2. The mixture was stirred a t room temperature for 7 h. The usual workup and chromatography (SiOz, benzene-AcOEt (101)) provided 2a (16 mg, 86%) as a colorless oil. The synthetic 2a was homogeneous on VPC 4+3m, 170 "C), and ita IR and NMR spectra were superimposable with those of the authentic sample (Shinetsu). Similarly, 1 and 2b were prepared from 17 and 18b in 84 and 85% yield, respectively. The published spectral data of 1,2a, and 2b were in 1980,45, 20-24 agreement with those of the synthetic sample^.'^ RegistryThe chemistry of aloe-emodin (3) has been explored with a view toward its use as a synthon for the regioepecific synthesis of adriamycin and analogues of it. Routes for satisfactory large-scale monomethyl ether formation at CB (4) and regiospecific introduction of a phenolic oxygen function a t C4 (21) are described. Interesting side reactions were encountered, including an apparent peri 0 to 0 acyl wandering reaction during methylation and a reductive debromination reaction during displacement of an aryl bromide by methanolic methoxide.Aloe-emodin (4) has been converted in six steps to 1,4,5-trihydroxy-2-(2,3-dicarboxypropyl)-9,lO-ant~aquinone (17), a synthon suitable for further regiospecific elaboration into daunomycin-adriamycin analogues. A method for Friedel-Crafts acylation of anthraquinones by reduction to the anthracenone, cyclization, and reoxidation has been developed as a key feature of the synthesis.

The Lactone Concept: An Efficient Pathway to Axially Chiral Natural Products and Useful Reagents

“…172 With these problems solved, it seemed rewarding to try the authentic synthesis of knipholone (0-) starting from aloe-emodin () (Scheme 50). The introduction of bromine into the 4-position of had already been described in the literature, 173 by specific bromination of its diacetate to give but regrettably the bromine goes into the wrong 2-position, exclusively, as clearly seen by NMR. 172 Steric blocking of the 'northern part' of aloe-emodin () by 2-isopropylation to give , finally forced the bromine to go into the correct position giving the required 4bromo product , as also proven by an X-ray structure analysis (Scheme 50).…”

Oxidative Degradation of Cardiotoxic Anticancer Anthracyclines to Phthalic Acids

“…Previously, the formation of 3-methoxyphthalic acid or other products of ring D oxidation (like e.g. 3-methoxysalycilic acid) was only observed under artificial conditions such as permanganate oxidation of investigational anthraquinones (35) or riboflavin-mediated photooxidation of DOX (36). IV ϭO (peaks at 546 and 586 nm).…”

Photochemistry and Phototoxicity of Aloe Emodin¶

“…All solvents were of spectroscopic grade and were used without purification. 1,8‐Dimethoxy‐3‐(hydroxymethyl)‐9,10‐anthraquinone was prepared according to the procedure described by Alexander et al (6), and its 1 H NMR was consistent with the literature spectrum.…”