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The Michael addition reaction is widely recognized as one of the most general methods for formation of C-C bonds in organic synthesis, 1 and the development of enantioselective catalytic conjugate addition reaction has been subject of intensive research.2 In addition to the great success catalyzed by metal complexes, the powerful and environmentally friendly organocatalyst-mediated asymmetric conjugate addition reaction has been explored intensively in recent years. 3,4Enantioselective organocatalytic conjugate addition reaction of β-ketoesters to α,β-unsaturated carbonyl compounds represents a direct and most appealing approach to chiral 1,5-dicarbonyl compounds that are versatile intermediates in organic synthesis.5 Particularly, the addition of 4-hydroxycoumarin to α,β-unsaturated ketones is a straightforward method to access warfarin which is an effective anticoagulants. Further investigation showed that (S)-warfarin had higher anticoagulant activity than the R enantiomer.6 As a result, achieving the optically pure R or S enantiomer of warfarin would be of great importance. Among the established strategies for the synthesis of chiral warfarin, chiral auxiliary strategy, hydrogenation, and hetero-Diels-Alder reaction have been intensively studied.7 Recently, several groups reported an enantioselective conjugate addition reaction of 4-hydroxycoumarin to enones, catalyzed by chiral secondary amines, primary amines, and bifunctional primaryamine thioureas.8 Although several efficient methods have been achieved by these systems, an effective method for the synthesis of warfarin is still a challenge.As part of the research program related to the development of synthetic methods for the enantioselective construction of stereogenic carbon centers, 9 we recently reported asymmetric conjugate addition reaction of active methylenes and methines.10 Herein, we wish to describe the enantioselective asymmetric conjugate addition of 4-hydroxycoumarin to α,β-unsaturated ketones promoted by binaphthyl-modified primary amine organocatalyst.Validation of the feasibility of the proposed Michael addition process started by evaluating a model reaction between 4-hydroxycoumarin (1) with (E)-4-phenylbut-3-en-2-one (2a) in the presence of 20 mol % bifunctional catalysts (Fig.

Enantioselective Decarboxylative Aldol Addition of β-Ketoacids to Isatins Catalyzed by Binaphthyl-Modified Organocatalyst. -Optimized reaction conditions using a squaric acid diamide derivative as the catalyst are developed for the title reaction to afford phenacyloxindole derivatives with excellent enantioselectivity. The reaction can be scaled up. -(SUH, C. W.; CHANG, C. W.; CHOI, K. W.; LIM, Y. J.; KIM*, D. Y.; Tetrahedron Lett. 54 (2013) 28, 3651-3654, http://dx.

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As a companion and hunting dog, height, length, length to height ratio (LHR) and body-weight are the vital economic traits for Jindo dog. Artificial breeding has produced an extraordinary diversity in these traits. Therefore, the identification of causative markers, genes and pathways that led us to understand the genetic basis of this variability is essential for their selection purposes. Here, we performed a genome-wide association study (GWAS) combined with pathway-based analysis on 757 dogs using 118,879 SNPs. A higher heritability (h2) was detected for height (0.33) and weight (0.28) trait in Jindo. At a threshold of p-value < 5E-05, 10, 6, 13, and 11 SNPs on different chromosomes were significantly associated with height, length, LHR and body-weight traits, respectively. Based on our result, HHIP, LCORL, and NCAPG for height, IGFI and FGFR3 for length, DLK1 and EFEMP1 for LHR, and PTPN2, IGFI, and RASAL2 for weight can be the potential candidate genes because the significant SNPs located in their intronic or upstream regions. An additive and dominant mode of inheritance was noticed from the phenotype-genotype correlation plot for top variants. The gene-set enrichment analysis highlighted here 9 and 7 overlapping significant (p < 0.05) GO terms and pathways among traits. Interestingly, the highlighted pathways were related to hormone synthesis, secretion and signaling were generally involved in the metabolism, growth and development process. Our data provide an insight into the significant genes and pathways if verified further, which will have a significant effect on the breeding /management of the Jindo dog’s population.