Total Syntheses of 2,2‘-epi-Cytoskyrin A, Rugulosin, and the Alleged Structure of Rugulin

Abstract

The total syntheses of 2,2'-epi-cytoskyrin A, rugulosin, and the alleged structure of rugulin are described. These naturally occurring bisanthraquinones and their relatives are characterized by novel molecular architectures at the core, at which lies a more or less complete, cage-like structural motif termed "skyrane". The strategies developed for their total synthesis feature a cascade sequence called the "cytoskyrin cascade" and deliver these molecules in short order and in a stereoselective manner.

Total Synthesis and Biological Evaluation of (+)- and (−)-Bisanthraquinone Antibiotic BE-43472B and Related Compounds

“…Thus, exposure of the known aryl ketone 9 8 to LiHMDS (1.0 equiv, THF, –78 °C) followed by quenching of the resulting enolate with enetrione 10 8,9 furnished, in quantitative yield, the desired racemic Michael adducts 11 and epi - 11 , which upon flash column chromatography (silica) equilibrated to ca. 1:1 mixture of inseparable epimers.…”

“…For building block 8 and related fragments, we developed an improved synthesis through modification of our previous route8 based on the Hauser annulation reaction. The required nitrile components 19a and 19b were prepared as shown in Scheme 3.…”

The art of total synthesis through cascade reactions

“…Intrigued by the relatively simple chemistry postulated to lead to these complex cage-like systems, we set out to discover an efficient cascade pathway to cytoskyrin-type molecules in the laboratory, and reported the so-called cytoskyrin cascades in 2005 24. In our model study with a substrate lacking the C2-hydroxyl group (see 67 , Figure 6), we discovered that each of the requisite transformations could be accomplished through judicious use of only the simplest of reagents, namely MnO 2 , CSA, and/or Et 3 N. Furthermore, through careful tuning of reaction conditions, any or all of the synthetic steps could be combined in a cascade sequence.…”

Multiple reactivities of dithranol towards 1-alkynyl Fischer carbene complexes (CO)5MC(OEt)CCPh (M=Cr, W) – Efficient chemical synthesis of aromatic polyketides

“…Compound 7 may also act as a versatile bioactive agent through hydrolysis of its lactone group [22] and in fact the pentangular structure of 7 is very similar to that of antitumor agents benastatins [23]. The polyphenolic derivatives 9 and 12, and their Table 1 Reactions of 1 and 2. possible hydrolyzed forms also exhibit structures analogous to the substructures of many natural aromatic polyketide-derived products or bioactive agents [24][25][26].…”