Spiro[1,2]oxaphosphetanes of Nonstabilized and Semistabilized Phosphorus Ylide Derivatives: Synthesis and Kinetic and Computational Study of Their Thermolysis.

A series of tri- and tetrasubstituted spiro-oxaphosphetanes stabilized by ortho-benzamide (oBA) and N-methyl ortho-benzamide (MoBA) ligands have been synthesized by the reaction of Cα,Cortho-dilithiated phosphazenes with aldehydes and ketones. They include enantiopure products and the first example of an isolated oxaphosphetane having a phenyl substituent at C3 of the ring. Kinetic studies of their thermal decomposition showed that the process takes place irreversibly through a polar transition state (ρ = -0.22) under the influence of electronic, [1,2], [1,3] steric, and solvent effects, with C3/P-[1,2] interactions as the largest contribution to ΔG⧧ of olefination. Inversion of the phosphorus configuration through stereomutation has been observed in a number of cases. DFT calculations showed that oBA derivatives olefinated through the isolated (N, O)(Ph, C6H4, C) oxaphosphetanes (Channel A), whereas MoBA compounds decomposed faster via the isomer (C6H4, O)(C, N, Ph) formed by P-stereomutation involving a MB2 permutational mechanism (Channel B). The energy barrier of P-isomerization is lower than that of olefination. Fragmentation takes place in a concerted asynchronous reaction. The thermal stability of oxaphosphetanes is determined by strong C3/P-[1,2] interactions destabilizing the transition state of olefination. The effect of charge distribution and C3/C4-[1,2] and C4/P-[1,3] steric and solvent interactions on ΔG⧧ was also evaluated.

In vitro evaluation of anthraquinones from Aloe vera (Aloe barbadensis Miller) roots and several derivatives against strains of influenza virus.

Aloe vera is a crop of wide economic value of worldwide distribution, and a rich source of quinone components. Recently, antiviral aloe anthraquinones had been reported against human influenza virus. In the present work two anthraquinones, aloesaponarin-I (1) and aloesaponarin-II (2) were isolated from A. vera roots, and six derivatives were obtained by methylation (3), acetylation (4) and O-glycosyl (5-6) reactions starting from (1). Additionally, a new Tetra-O-acetyl-ß-d-glucopyranosyl derivative from 2 was also prepared. All compounds were evaluated against two strains of influenza virus AH1N1 by cytopathic effect reduction assay (CPE). The antiviral activity was determined by the ability of compounds to inhibit virus replication on Madin Darby Canine Kidney cells (MDCK). New derivatives 3-(2´,3´,4´,6´-Tetra-O-acetyl-ß-d-glucopyranosyl-aloesaponarin-I (5) and 3-(2´,3´,4´,6´-Tetra-O-acetyl-ß-d-glucopyranosyl- aloesaponarin-II (7) showed a cytopathic reduction effect against influenza strain A/Yucatán/2370/09 with IC50 of 30.77 and 13.70 µM, and against the virus A/Mexico/InDRE797/10 with IC50 of 62.28 and 19.47 µM, respectively. To assess the effect of derivatives 5 and 7 during one cycle of replication (0-10 h), a time-of-addition experiment was performed. As a result it was found that both compounds were most effective when added 6-10 h post-infection and significantly inhibited viral titre (> 70%) at the concentrations of 50 and 100 µM. Based on the structural analysis of the compounds, it was suggested that the Tetra-O-acetyl-ß-d-glucopyranosyl substituent at the C3 position of the anthraquinone might have an effect against the influenza AH1N1 virus.

Genomic Regions Associated with Resistance to Gastrointestinal Parasites in Australian Merino Sheep.

The objective of this study was to identify genomic regions and genes associated with resistance to gastrointestinal nematodes in Australian Merino sheep in Uruguay, using the single-step GWAS methodology (ssGWAS), which is based on genomic estimated breeding values (GEBVs) obtained from a combination of pedigree, genomic, and phenotypic data. This methodology converts GEBVs into SNP effects. The analysis included 26,638 animals with fecal egg count (FEC) records obtained in two independent parasitic cycles (FEC1 and FEC2) and 1700 50K SNP genotypes. The comparison of genomic regions was based on genetic variances (gVar(%)) explained by non-overlapping regions of 20 SNPs. For FEC1 and FEC2, 18 and 22 genomic windows exceeded the significance threshold (gVar(%) ≥ 0.22%), respectively. The genomic regions with strong associations with FEC1 were located on chromosomes OAR 2, 6, 11, 21, and 25, and for FEC2 on OAR 5, 6, and 11. The proportion of genetic variance attributed to the top windows was 0.83% and 1.9% for FEC1 and FEC2, respectively. The 33 candidate genes shared between the two traits were subjected to enrichment analysis, revealing a marked enrichment in biological processes related to immune system functions. These results contribute to the understanding of the genetics underlying gastrointestinal parasite resistance and its implications for other productive and welfare traits in animal breeding programs.

Identification of Candidate Genes and Pathways Linked to the Temperament Trait in Sheep.

Temperament can be defined as the emotional variability among animals of the same species in response to the same stimulus, grouping animals by their reactivity as nervous, intermediate, or calm. Our goal was to identify genomic regions with the temperament phenotype measured by the Isolation Box Test (IBT) by single-step genome-wide association studies (ssGWAS). The database consisted of 4317 animals with temperament records, and 1697 genotyped animals with 38,268 effective Single Nucleotide Polymorphism (SNP) after quality control. We identified three genomic regions that explained the greatest percentage of the genetic variance, resulting in 25 SNP associated with candidate genes on chromosomes 6, 10, and 21. A total of nine candidate genes are reported for the temperament trait, which is: PYGM, SYVN1, CAPN1, FADS1, SYT7, GRID2, GPRIN3, EEF1A1 and FRY, linked to the energetic activity of the organism, synaptic transmission, meat tenderness, and calcium associated activities. This is the first study to identify these genetic variants associated with temperament in sheep, which could be used as molecular markers in future behavioral research.

Chemical constituents of Pithecellobium albicans.

A new ent-kaurane diterpene glycoside identified as (-)19-beta-D-glucopyranosyl 6,7-dihydroxy kaurenoate, was isolated from the seeds of Pithecellobium albicans. The structure of the new compound was established by spectral data.

Racemochrysone, a dihydroanthracenone from Senna racemosa.

From the hexane extract of the bark of the stems of Senna racemosa (syn. Cassia racemosa) a new dihydroanthracenone derivative, named racemochrysone, was isolated. Its structure was established as 8,9-dihydroxy-3-methoxy-2,2,6-trimethyl-(2H)-anthracen-1-one based on spectroscopical data, mainly 1D and 2D NMR experiments. In addition beta-sitosterol, stigmasterol, chrysophanol and physcion were obtained. From the leaves extracts the piperidine alkaloid cassine and the hexitol pinitol were obtained.