ABSTRACT
Asymmetric enamine alkylation represents a powerful tool for stereoselective C-C bond formation; in contrast, the development of enantioselective enamine acylation remains elusive. Here, we report that a chiral phosphoric acid can render an in-situ-formed enamine to undergo a stereoselective intramolecular α-carbon acylation, providing an alternative approach for the synthesis of useful pyrrolinones and indolinones bearing tetrasubstituted stereocenters. Utilizing an effective integration of the desymmetrization strategy and bifunctional organocatalysis, the first example of enantioselective enamine acylation is achieved by employing readily available aminomalonic esters and cyclic ketones. Instead of reactive and moisture-sensitive acyl chlorides, common esters with low electrophilicity were successfully used as efficient acylating reagents via hydrogen bonding interactions. The utility is demonstrated in the concise and enantioselective synthesis of (+)-LipidGreen I and II. Experimental studies and DFT calculations establish the reaction pathway and the origin of stereocontrol.
ABSTRACT
The Biltz synthesis establishes straightforward access to 5,5-disubstituted (thio)hydantoins by combining a 1,2-diketone and a (thio)urea. Its appealing features include inherent atom and step economy together with the potential to generate structurally diverse products. However, control of the stereochemistry of this reaction has proven to be a daunting challenge. Herein, we describe the first example of enantioselective catalytic Biltz synthesis which affords more than 40 thiohydantoins with high stereo- and regio-control, irrespective of the symmetry of thiourea structure. A one pot synthesis of corresponding hydantoins is also documented. Remarkably, experimental studies and DFT calculations establish the reaction pathway and origin of stereoselectivity.
ABSTRACT
BACKGROUND: Few studies have evaluated the long-term relationship between diet quality and cardiometabolic risk factor clustering among children. The moderating effect of socio-economic status (SES) is of interest. OBJECTIVE: To investigate the association between diet quality with cardiometabolic risk among Chinese children and to explore the moderating effect of SES. DESIGN: In this cohort study, 5 waves (1997-2009) of the China Health and Nutrition Survey were used. Diet quality was measured by a modified version of the Chinese Children Dietary Index (mCCDI) based on Dietary Guidelines for Chinese. PARTICIPANTS: Children between the ages of 7 and 17 (n = 2903) who completed at least 2 surveys were included. Those who missed measures or had hypertension or diabetes at baseline were excluded. MAIN OUTCOME MEASURES: The fasting blood samples were collected in 2009. Waist circumference (WC) and blood pressure (BP) were measured in each survey. STATISTICAL ANALYSIS PERFORMED: A continuous cardiometabolic risk score (MetScore) was derived by a confirmatory factor analysis of 5 components: WC, BP, glucose, triglycerides, and high-density lipoprotein cholesterol. Considering the latency period of the effect of behaviors, the mCCDI was lagged by the period between surveys. Linear regression was used to analyze the association of mCCDI with MetScore and its components. Mixed effect linear regression and lagged mCCDI were used for WC and BP models. RESULTS: Higher mCCDI was independently associated with a lower MetScore at follow-up (ß: -.11; 95% CI: -.18 to -.04). Higher lagged mCCDI over time was associated with a lower WC z score overall (ß: -.05; 95% CI: -.08 to -.01) and among children in the low SES group (ß: -.09; 95% CI: -.14 to -.04) but not those in the high SES group. When examining the 15 mCDDI components separately, scores for 5 components: more grains, vegetables, soybeans and its products; less sugar-sweetened beverages; and more diet variety were significantly associated with a lower MetScore. CONCLUSIONS: Among Chinese children, higher diet quality measured by mCCDI was independently associated with a lower MetScore at follow-up.