14,17-Epidioxy-28-nor-15-taraxerene-2,3-diol

Double Diastereoselective Approach to Chiral syn- and anti-1,3-Diol Analogues through Consecutive Catalytic Asymmetric Borylations.[Pubmed:28628323]

J Org Chem. 2017 Jul 21;82(14):7265-7279.

Homoallylic boronate carboxylate esters derived from unsaturated aldehydes via an imination, beta-borylation, imine hydrolysis, and Wittig trapping sequence, were subjected to a second boryl addition to give 1,3-diborylated carboxylate esters. Control of the absolute and relative stereochemistry of the two new 1,3-stereogenic centers was achieved through: (1) direct chiral catalyst controlled asymmetric borylation of the first stereocenter on the unsaturated imine with high e.e.; and (2) a double diastereoselectively controlled borylation of an unsaturated ester employing a chiral catalyst to largely overcome directing effects from the first chiral boryl center to give poor (mismatched) to good (matched) diastereocontrol. Subsequently, the two C-B functions were transformed into C-O systems to allow unambiguous stereochemical assignment of the two borylation reactions involving oxidation and acetal formation.

New Cytotoxic Secondary Metabolites from Marine Bryozoan Cryptosula pallasiana.[Pubmed:28406457]

Mar Drugs. 2017 Apr 13;15(4). pii: md15040120.

A new sterol, (23R)-methoxycholest-5,24-dien-3beta-ol (1), two new ceramides, (2S,3R,4E,8E)-2-(tetradecanoylamino)-4,8-octadecadien-l,3-diol (6) and (2S,3R,2'R,4E,8E)-2-(tetradecanoylamino)-4,8-octadecadien-l,3,2'-triol (7), together with three known sterols (2-4), a lactone (5) and two ceramides (8,9), were isolated from the marine bryozoan Cryptosula pallasiana, collected at Huang Island of China. The structures of the new compounds were elucidated by extensive spectroscopic analyses, chemical methods and quantum electronic circular dichroism (ECD) calculations. Among the isolated compounds, sterol 1 possessed a rare side chain with a methoxy group at C-23, and a double bond between C-24 and C-25. Ceramides 6 and 7 possessed 14 carbons in their long-chain fatty acid base (FAB), which were different from the normal ceramides with 16 carbons in the FAB. Moreover, compounds 5 and 8 were isolated for the first time from marine bryozoans. Compounds 1-9 were evaluated for their cytotoxicity against human tumor cell lines HL-60, Hep-G2 and SGC-7901. The results showed that lactone 5 appears to have strong cytotoxicity against the test tumor cell lines, with IC50 values from 4.12 muM to 7.32 muM, and sterol 1 displayed moderate cytotoxicity with IC50 values between 12.34 muM and 18.37 muM, while ceramides 6-9 showed weak cytotoxicity with IC50 ranging from 21.13 muM to 58.15 muM.

Bioactive Sesquiterpenes from the Edible Mushroom Flammulina velutipes and Their Biosynthetic Pathway Confirmed by Genome Analysis and Chemical Evidence.[Pubmed:27684789]

J Org Chem. 2016 Oct 21;81(20):9867-9877.

Twelve putative sesquiterpene synthases genes were found in clades along with enzymes with 1,6-, 1,10-, and 1,11-cyclase activities in the genome of Flammulina velutipes. Chemistry investigation of F. velutipes led to the identification of two seco-cuparane sesquiterpenes, flammufuranone A (1) and B (2); 13 new sesquiterpenes with nor-eudesmane, spiroaxane, cadinane, and cuparane skeletons (3-14, 16); as well as two new ergosterol derivatives (17 and 18). Sesquiterpenes (3-14) derived from 1,10-cyclizing enzyme were first reported from this mushroom. The absolute configurations in 1 (3R,7S) and 2 (3R,7R) were assigned by electronic circular dichroism (ECD) calculation. The absolute configuration in 3 was confirmed by X-ray diffraction analysis. The absolute configurations in the 1,2-diol moiety of 13, and in the 1,3-diol moiety of 17 and 18 were determined using Snatzke's method. Among these compounds, 3, 5, 13, and 14 were found to inhibit the HMG-CoA reductase with IC50 of 114.7, 77.6, 55.5, and 87.1 muM, respectively. Compounds 5, 6, 7, 10, 13, and 14 showed DPP-4 inhibitory activity with IC50 of 75.9, 83.7, 70.9, 79.7, 80.5, and 74.8 muM, respectively. The biosynthesis for sesquiterpenes in F. velutipes was also discussed.

Short communication: Analytical method and amount of preservative added to milk samples may alter milk urea nitrogen measurements.[Pubmed:27988113]

J Dairy Sci. 2017 Feb;100(2):1502-1506.

Milk urea N (MUN) is used by dairy nutritionists and producers to monitor dietary protein intake and is indicative of N utilization in lactating dairy cows. Two experiments were conducted to explore discrepancies in MUN results provided by 3 milk processing laboratories using different methods. An additional experiment was conducted to evaluate the effect of 2-bromo-2-nitropropane-1, 3-diol (bronopol) on MUN analysis. In experiment 1, 10 replicates of bulk tank milk samples, collected from the Pennsylvania State University's Dairy Center over 5 consecutive days, were sent to 3 milk processing laboratories in Pennsylvania. Average MUN differed between laboratory A (14.9 +/- 0.40 mg/dL; analyzed on MilkoScan 4000; Foss, Hillerod, Denmark), laboratory B (6.5 +/- 0.17 mg/dL; MilkoScan FT + 6000), and laboratory C (7.4 +/- 0.36 mg/dL; MilkoScan 6000). In experiment 2, milk samples were spiked with urea at 0 (7.3 to 15.0 mg/dL, depending on the laboratory analyzing the samples), 17.2, 34.2, and 51.5 mg/dL of milk. Two 35-mL samples from each urea level were sent to the 3 laboratories used in experiment 1. Average analyzed MUN was greater than predicted (calculated for each laboratory based on the control; 0 mg of added urea): for laboratory A (23.2 vs. 21.0 mg/dL), laboratory B (18.0 vs. 13.3 mg/dL), and laboratory C (20.6 vs. 15.2 mg/dL). In experiment 3, replicated milk samples were preserved with 0 to 1.35 mg of bronopol/mL of milk and submitted to one milk processing laboratory that analyzed MUN using 2 different methods. Milk samples with increasing amounts of bronopol ranged in MUN concentration from 7.7 to 11.9 mg/dL and from 9.0 to 9.3 mg/dL when analyzed on MilkoScan 4000 or CL 10 (EuroChem, Moscow, Russia), respectively. In conclusion, measured MUN concentrations varied due to analytical procedure used by milk processing laboratories and were affected by the amount of bronopol used to preserve milk sample, when milk was analyzed using a mid-infrared analyzer. Thus, it is important to maintain consistency in milk sample preservation and analysis to ensure precision of MUN results.

Isolation of a new resorcinolic lipid from Mangifera zeylanica Hook.f. bark and its cytotoxic and apoptotic potential.[Pubmed:28222398]

Biomed Pharmacother. 2017 May;89:194-200.

Mangifera zeylanica is a plant endemic to Sri Lanka and its bark has been used in traditional medicine to treat some cancers. This study was aimed to isolate potentially cytotoxic compound/s from the hexane extract of the bark of M. zeylanica by bio-activity guided fractionation. The structure of the isolated compound (1) was elucidated using (1)H, (13)C NMR and mass spectrometric techniques. Compound 1 was identified as a new resorcinolic lipid (5-((8Z, 11Z, 14Z)-hexatriaconta-8, 11, 14-trienyl) benzene-1,3-diol). Apoptotic potential of the isolated compound was determined only in MCF-7 (estrogen receptor positive) breast cancer cells to which it was more cytotoxic than to normal mammary epithelial cells. Oxidative stress markers [reactive oxygen species (ROS), glutathione levels (GSH) and glutathione-S-transferase (GSH)] were also determined in MCF-7 cells treated with compound 1. Treatment with compound 1 led to an increase in caspase 7 activity, morphological features of apoptosis and DNA fragmentation in MCF-7 cells. Furthermore, it also led to an increase in ROS and GST levels while depleting GSH levels. Results of this study suggest that isolated new resorcinolic lipid can induce apoptosis in MCF-7 cells, possibly via oxidative stress mechanism.