109273-98-5Relevant articles and documents
Cytotoxic dehydromonacolins from red yeast rice
Zhu, Lin,Yau, Lee-Fong,Lu, Jing-Guang,Zhu, Guo-Yuan,Wang, Jing-Rong,Han, Quan-Bin,Hsiao, Wen-Luan,Jiang, Zhi-Hong
, p. 934 - 939 (2012)
Two new dehydromonacolins (1 and 3), together with nine known monacolins (4-12), were isolated from red yeast rice. Compounds 4-6 were isolated from a natural resource for the first time. Their structures were elucidated by means of NMR and mass spectroscopic analyses. The structure of dehydromonacolin N (1) was further confirmed by its semisynthesis from monacolin K (lovastatin) (11). Dehydromonacolin J (2), an intermediate in the semisynthesis of 1, was obtained as a new dehydromonacolin. The structure of dehydromonacolin L (3) was also confirmed by an elimination reaction of monacolin L (12). Compound 1, possessing a C2 side chain, is unprecedented in the natural monacolin family and exhibited moderate cytotoxic activity against Hep G2, Caco-2, and MCF-7 cancer cell lines. Dehydromonacolin K (8) demonstrated the most potent cytotoxicity to all three of these cell lines. The structure-activity relationship of natural and synthesized monacolins was discussed. This is the first report on the cytotoxic effects of dehydromonacolins.
Statin-derived 1,3-oxazinan-2-ones as submicromolar inhibitors of LFA-1/ICAM-1 interaction: Stabilization of the metabolically labile vanillyl side chain
Ullrich, Thomas,Baumann, Karl,Welzenbach, Karl,Schmutz, Simone,Camenisch, Gian,Meingassner, Josef G.,Weitz-Schmidt, Gabriele
, p. 2483 - 2487 (2007/10/03)
Modification of the vanillyl substituent on a potent, semisynthetic lymphocyte function-associated antigen (LFA)-1/intercellular adhesion molecule (ICAM)-1 binding inhibitor of the statin family resulted in metabolically more stable analogues that displayed submicromolar inhibitory activity in vitro and considerable anti-inflammatory activity in vivo. The benzodioxole derivative 2b emerged with the best overall profile.
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.
CONVENIENT TWO-STEP STEREOSPECIFIC HYDROXY-SUBSTITUTION WITH RETENTION IN β-HYDROXY-δ-LACTONES. 4(R)-HETEROSUBSTITUTED MEVINOLIN AND -ANALOGS
Bartmann, W.,Beck, G.,Granzer, E.,Jendralla, H.,Kerekjarto, B. v.,Wess, G.
, p. 4709 - 4712 (2007/10/02)
Michael additions of mercaptanes and amines to optically pure 6-alkyl-5,6-dihydro-2H-pyran-2-ones of the mevinolin type -5 and the aromatic analog -7 are stereospecific to give 4(R)-substituted mevinolin analogs.
