Total Synthesis of Anthracyclinone [New Synthetic Methods (60)]

Abstract

The remarkable antitumor properties of anthracycline antibiotics have motivated synthetic chemists, and a large number of groups have been active recently in this field. Initially, there was very little hope for this class of substances due to their extreme toxicity. However, the dividing line between toxicity and desired pharmacological effect has broadened to such an extent, partly through microbiological methods (new strains, mutants) and partly through semisynthetic modifications, that today anthracyclines take number one place (over 20% of the market) in the chemotherapy of (human) cancer. The demands made on modern cytostatica are extremely high, as may be seen from the fact that of the more than 600000 drugs tested in animals, only about 40 are in clinical use. In the meantime, some anthracyclines obtained by total synthesis are also in clinical testing. In this review it will hopefully be demonstrated that all those concerned in the chemotherapeutic use of these substances have also contributed to the general progress made in the solution of regio-and stereochemical problems of linearly annelated ring systems.

Protein Kinase Inhibitors from Microorganisms

“…8.12; 75), the first member of a very interesting bisindolobenzoquinone class of compounds, in the year 1975, from Chaetomium sp., as antifungal antibiotic compound. Since then several benzoquinones, such as asterriquinones [81][82][83][84] (76)(77)(78)(79)(80)(81)(82)(83)(84), isocochliodinol (85), semicochliodinols (86, 87) [89], and terphenylquinones (88)(89)(90)(91)(92), were isolated [90][91][92]. Although asterriquinones were well recognized for their antibiotic and antitumour activity [87], it took around 25 years to realize their kinase inhibitory potential [85,86,88].…”

A Chemoenzymatic, Enantioconvergent, Asymmetric Total Synthesis of(R)‐Fridamycin E

“…: [5] 164-165°C). 1 Oxidative Cleavage of (R)-5 and Transformation to (R)-Fridamycin E Methyl Ester: NaIO 4 (206 mg, 0.97 mmol, 8 equiv.) was added to a solution of (R)-5 (37 mg, 0.12 mmol) in acetone/water (9:1, 2 mL) and the mixture was cooled to 0°C.…”

“…The clinical utility of anthracyclines and their analogs in chemotherapy has initiated many efforts directed towards their synthesis. [1,2] Typically, anthracyclines consist of an anthraquinone nucleus bearing one or more sugar moieties attached through O-glycosidic bonds. However, an intriguing subclass of structurally related compounds exists in which the carbohydrate is linked by a C-glycosidic bond, prominent representatives of which are the vineomycin [3] and fridamycin families.…”

Regiodefined synthesis of brominated hydroxyanthraquinones related to proisocrinins

“…A brief literature survey revealed that the routes for the synthesis of anthraquinones are primarily based upon five categories, such as Friedel–Crafts reactions, Hauser annulations, Diels–Alder reactions, transition metal-mediated reactions and biomimetic aldol condensations [ 17 – 23 ], and reports on the synthesis of brominated anthraquinones are scare [ 12 – 15 ]. Having inspired by the convergence and the regiochemical integrity of the Hauser annulation [ 24 – 30 ], we explored it for the construction of the bromoanthraquinone scaffolds of proisocrinins 6 – 11 .…”