Zurwerra, Didier; Glaus, Florian; Betschart, Leo; Schuster, Julia; Gertsch, Juerg; Ganci, Walter; Altmann, Karl-Heinz published the artcile< Total synthesis of (-)-zampanolide and structure-activity relationship studies on (-)-dactylolide derivatives>, Synthetic Route of 617-55-0, the main research area is zampanolide asym total synthesis antitumor structure activity relationship; dactylolide asym total synthesis antitumor structure activity relationship.
A new total synthesis of the marine macrolide (-)-zampanolide (I) and the structurally and stereochem. related non-natural levorotatory enantiomer (II) of (+)-dactylolide was developed. The synthesis features a high-yielding, selective intramol. Horner-Wadsworth-Emmons (HWE) reaction to close the 20-membered macrolactone ring of I and II. The β-keto phosphonate/aldehyde precursor for the ring-closure reaction was obtained by esterification of a ω-di-Et phosphono carboxylic acid fragment and a secondary alc. fragment incorporating the THP ring that is embedded in the macrocyclic core structure of I and II. THP ring formation was accomplished through a segment coupling Prins-type cyclization. Employing the same overall strategy, 13-desmethylene-II as well as the monocyclic desTHP derivatives of I and II were prepared Synthetic I inhibited human cancer cell growth in vitro with nanomolar IC50 values, while II, which lacks the diene-containing hemiaminal-linked side-chain of I, is 25- to 260-fold less active. 13-Desmethylene-II as well as the reduced versions of II and 13-desmethylene-II all showed similar cellular activity as II itself. The same activity level was attained by the monocyclic desTHP derivative of I. Oxidation of the aldehyde functionality of II gave a carboxylic acid that was converted into the corresponding N-hexyl amide. The latter showed only micromolar antiproliferative activity, thus being several 100-fold less potent than I.
Chemistry – A European Journal published new progress about Antitumor agents. 617-55-0 belongs to class esters-buliding-blocks, and the molecular formula is C6H10O5, Synthetic Route of 617-55-0.
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