Enantioselective synthesis of (-)-wikstromol using a new approach via malic acid.
The total synthesis of (-)-wikstromol, a bioactive alpha-hydroxylated lactone lignan, from natural malic acid using a consecutive alkylation strategy is presented. First, alkylation of a malic acid ester provided the monobenzyl derivative, which was then converted to an alpha-substituted dioxolanone. This derivative was reacted in a second alkylation step to a double benzylated dioxolanone, which was transformed to bis-O-benzyl-protected (-)-wikstromol and subsequently to the natural product. Only six steps were required to produce wikstromol in 30% overall yield. A second approach from malic acid, the double alkylation of dienolates from 5-oxo-1,3-dioxolan-4-yl acetic acid derivatives, was not successful. No reaction conditions were found to afford the dienolates. Instead, rapid fragmentation of the dioxolanones to fumaric acid derivatives and pivalaldehyde occurred even at -105 degrees C, and aldol reaction products with good stereoselectivity were formed. The relative configuration of the major isomer was determined by X-ray structure analysis. By comparison of NMR data it is shown that a previous assignment of the configuration of one of the described aldol products was incorrect.
Institut für Organische Chemie und Strukturanalytik, Universität Potsdam, Karl-Liebknecht-Strasse 24-25, 14476 Golm, Germany. sefkow@rz.uni-postdam.de
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D000478:Alkylation; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis*; D018360:Crystallography, X-Ray; D005663:Furans / Q000138:chemical synthesis*; D017705:Lignans / Q000138:chemical synthesis*; D009682:Magnetic Resonance Spectroscopy; D008293:Malates / Q000737:chemistry*; D015394:Molecular Structure; D013237:Stereoisomerism
D000972:Antineoplastic Agents, Phytogenic; D005663:Furans; D017705:Lignans; D008293:Malates; C020436:nortrachelogenin; C030298:malic acid