58889-19-3Relevant articles and documents
Transformations of cyclic nonaketides by Aspergillus terreus mutants blocked for lovastatin biosynthesis at the lovA and lovC genes
Sorensen, John L.,Auclair, Karine,Kennedy, Jonathan,Hutchinson, C. Richard,Vederas, John C.
, p. 50 - 59 (2007/10/03)
Two mutants of Aspergillus terreus with either the lovC or lovA genes disrupted were examined for their ability to transform nonaketides into lovastatin 1, a cholesterol-lowering drug. The lovC disruptant was able to efficiently convert dihydromonacolin L 5 or monacolin J 9 into 1, and could also transform desmethylmonacolin J 15 into compactin 3. In contrast, the lovA mutant has an unexpectedly active β-oxidation system and gives only small amounts of 1 upon addition of the immediate precursor 9, with most of the added nonaketide being degraded to heptaketide 22. Similarly, the lovA mutant does not accumulate the polyketide synthase product 5 and rapidly degrades any 5 added as a precursor via two cycles of β-oxidation and hydroxylation at C-6 to give 20. The possible involvement of epoxides 21a and 21b in the biosynthesis of 1 was also examined, but their instability in fermentation media and fungal cells will require purified enzymes to establish their role.
Total Syntheses of ML-236A and Compactin by Combining the Lactonic (Silyl) Enolate Rearrangement and Aldehyde-Diene Cyclocondensation Technologies
Danishefsky, Samuel J.,Simoneau, Bruno
, p. 2599 - 2604 (2007/10/02)
The sequence of a lactonic Claisen rearrangement and a Lewis acid catalyzed cyclocondensation of an aldehyde with an appropriate diene affords a new route to the title series.
