4627-51-4Relevant academic research and scientific papers
Synthesis of ent-crotonadiol and compounds related to it from (+)-larixol
Vlad,Chokyrlan,D'Ambrosio,Koltsa,Barba,Edu,Byryyak,Nikolescu,Mari,Deleanu
, p. 397 - 403 (2011)
A new synthesis of 13E-ent-crotonadiol and its 13Z-isomer from 6α-acetoxy-14,15-bis-norlabd-8(17)-en- 13-one is described. A mixture of methyl esters of 13E- and 13Z-6α-acetoxylabd-8(17),13-dien-15-oic and 13E- and 13Z-6α-hydroxylabd-8(17),13-dien-15-oic acids was formed by its reaction with trimethylphosphonoacetate. Mixtures of 13E- and 13Z-6α-hydroxylabd-8(17),13-dien-15-oic acids were formed by hydrolysis of this mixture. These were separated, methylated, and reduced by LiAlH 4 to give the pure 13E- and 13Z-crotonadiols in 64 and 16% yields, respectively. The two known syntheses of crotonadiol from (+)-larixol were reproduced. It was shown that they produced only 13E-crotonadiol.
Pharmacological inhibition of focal segmental glomerulosclerosis-related, gain of function mutants of TRPC6 channels by semi-synthetic derivatives of larixol
Urban, Nicole,Neuser, Sonja,Hentschel, Anika,K?hling, Sebastian,Rademann, J?rg,Schaefer, Michael
, p. 4099 - 4122 (2017/10/23)
Background and Purpose: Gain of function mutations in TRPC6 channels can cause autosomal dominant forms of focal segmental glomerulosclerosis (FSGS). Validated inhibitors of TRPC6 channels that are biologically active on FSGS-related TRPC6 mutants are eagerly sought. Experimental Approach: We synthesized new TRPC6-inhibiting modulators from larixol, a resiniferous constituent of Larix decidua, and tested the potency and selectivity in cell lines stably expressing various TRPC channel isoforms. Channel activation was followed by Ca2+ influx analyses and electrophysiological recordings. The most promising compound larixyl carbamate (LC) was tested on native TRPC6 channels and TRPC6 constructs carrying FSGS-related point mutations. Key Results: LC exhibited an about 30-fold preference for TRPC6 over TRPC3 channels and a fivefold preference for TRPC6 over TRPC7 channels. Six FSGS-related TRPC6 mutants, including the highly active M132T and R175Q variants, were strongly inhibited by 1?μM LC. Surprisingly, no TRPC6-related Ca2+ signals were detectable in primary murine podocytes, or in acutely isolated glomeruli. in these preparations. Quantitative PCR revealed a 20-fold to 50-fold lower abundance of TRPC6 transcripts in rat or mouse podocytes, compared with pulmonary artery smooth muscle cells from the same species. Accordingly, electrophysiological recordings demonstrated that DAG-induced currents in murine podocytes are very small, but sensitive to LC. Conclusions and Implications: In spite of their low abundance in native podocytes, native TRPC6 channels are targetable using larixol-derived TRPC6 inhibitors. As observed with wild-type TRPC6 channels, FSGS-related TRPC6 mutants were sensitive to the newly developed inhibitors, paving the way for experimental therapies.
MINOR COMPOUNDS OF THE OLEORESIN OF THE KAMCHATKA, JAPANESE, AND SIBERIAN LARCHES
Bol'shakova, V. I.,Shmidt, E. N.,Pentegova, V. A.,Mamatyuk, V. I.
, p. 536 - 541 (2007/10/02)
The polyfunctional compounds of the oleoresins of three species of larch have been studied.Larixol diacetate, 3β-hydroxyepimanool, and 15-oxopimara-4(14)-enoic 13-hydroxy-7-oxobicta-8(14)-enoic, 3β-hydroxysandaracopimaric, and 8,15-dihydroxyabietic acids have been isolated for the first time.The investigation performed has shown that the oleoresins of the larch contain polyfunctional compounds of various structural types.Depending on the species, their composition changes, and this fact can be used in the chemotaxonomy of larches.
