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Studies on mycophenolic acid and lignan chemistry

University of British Columbia

Previous work on the biosynthesis of mycophenolic acid is discussed. [1’-¹⁴C]-Orsellinic acid (22) and [1'-¹⁴C]-2,4-dihydroxy-5,6-dimethylbenzoic acid (23) were synthesized and administered to Penicillium brevi-compactum. The purpose of feeding these two acids was to determine the order or sequence of the reactions involved in the biosynthesis of mycophenolic acid. It was found that acid (22) was not incorporated into mycophenolic acid but that acid (23) was incorporated specifically to the extent of 11.5%. Degradation of the mycophenolic acid from the feeding of (23) showed that a completely specific incorporation had occurred and thus supported the role of this acid (23) as a precursor of mycophenolic acid. [1- ¹⁴C]-geraniol (24) was also fed in an attempt to determine the origin of the C₇ side chain of mycophenolic acid. (24) was incorporated but degradation of the mycophenolic acid showed that the geraniol was decomposed to acetate before incorporation, leaving the precursor status in doubt. Three attempts were made to synthesize mycophenolic acid using suspected biological intermediates with no success. This was presumably due to the difficulty encountered in trying to alkylate the aromatic skeleton of mycophenolic acid. A synthesis of lignans involving intramolecular phenolic oxidative coupling was attempted with little success, due to the inability to obtain the ester required to couple to give the lignan skeleton.

Text

2011-04-29

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http://hdl.handle.net/2429/34135

Chemistry

University of British Columbia

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