The catalytic asymmetric α-functionalization of prochiral barbituric acids, a subtype of pseudosymmetric 1,3-diamides, to yield the corresponding 5,5-disubstituted (quaternary) derivatives remains essentially unsolved. In this study 2-alkylthio-4,6-dioxopirimidines are designed as key 1,3-diamide surrogates that perform exceedingly in amine-squaramide catalyzed C-C bond forming reactions with vinyl ketones or Morita-Baylis-Hillmann-type allyl bromides as electrophiles. Mild acid hydrolysis of adducts affords barbituric acid derivatives with an in-ring quaternary carbon in unprecedented enantioselectivity, offering valuable materials for biological evaluations.

The asymmetric synthesis of tricyclic compounds by the desymmetrization of cyclohexadienones is presented. The reaction tolerated a large variety of substituents at different positions of the cyclohexadienone, and heterocyclic rings of different sizes were accessible. Density functional theory calculations showed that the reaction proceeds through an asynchronous [4+2] cycloaddition.

Here we report the highly enantio-and syn-selective synthesis of β-hydroxy α-amino acids from glycine imine derivatives under Brønsted base (BB) catalysis. The key of this approach is the use of benzophenone-derived imine of glycine o-nitroanilide as a pronucleophile, where the o-nitroanilide framework provides an efficient hydrogen-bonding platform that accounts for nucleophile reactivity and diastereoselectivity.

Background Polymerized allergens conjugated to non‐oxidized mannan (PM‐allergoids) are novel vaccines targeting dendritic cells (DCs). Previous experimental data indicate that PM‐allergoids are readily taken up by DCs and induce Treg cells. This first‐in‐human study was aimed to evaluate safety and to find the optimal dose of house dust mite PM‐allergoid (PM‐HDM) administered subcutaneously (SC) or sublingually (SL). Methods In a randomized, double‐blind, double‐dummy, placebo‐controlled trial, 196 subjects received placebo or PM‐HDM at 500, 1000, 3000, or 5000 mannan‐conjugated therapeutic units (mTU)/mL in 9‐arm groups for 4 months. All subjects received 5 SC doses (0.5 ml each) every 30 days plus 0.2 ml SL daily. The primary efficacy outcome was the improvement of titrated nasal provocation tests (NPT) with D. pteronyssinus at baseline and at the end of the study. All adverse events and reactions were recorded and assessed. Secondary outcomes were the combination of symptom and medication scores (CSMS) and serological markers. Results No moderate or severe adverse reactions were reported. Subjects improving the NPT after treatment ranged from 45% to 62% in active SC, 44% to 61% in active SL and 16% in placebo groups. Statistical differences between placebo and active groups were all significant above 500 mTU, being the highest with 3000 mTU SL (p = 0.004) and 5000 mTU SC (p = 0.011). CSMS improvement over placebo reached 70% (p < 0.001) in active 3000 mTU SC and 40% (p = 0.015) in 5000 mTU SL groups. Conclusions PM‐HDM immunotherapy was safe and successful in achieving primary and secondary clinical outcomes in SC and SL at either 3000 or 5000 mTU/ml.

The asymmetric synthesis of tricyclic compounds by the desymmetrization of cyclohexadienones is presented. The reaction tolerated a large variety of substituents at different positions of the cyclohexadienone, and heterocyclic rings of different sizes were accessible. Density functional theory calculations showed that the reaction proceeds through an asynchronous [4+2] cycloaddition.