Synthesis of functionalized tetrahydrodibenzo[b,g][1,8]naphthyridin-1(2H)-ones through base-promoted annulation of quinoline-derived dipolarophiles and cyclic enaminones.

An eco-friendly and metal-free method for the synthesis of tetrahydrodibenzo[b,g][1,8]naphthyridin-1(2H)-ones was established. Quinoline-derived dipolarophiles and cyclic enaminones as starting materials undergo a 1,4-Michael addition/SNAr tandem annulation reaction affording the target products. This approach features transition metal-free conditions, good functional group tolerance and operational simplicity.

Prenatal whole-exome sequencing for fetal structural anomalies: a retrospective analysis of 145 Chinese cases.

BACKGROUND: Whole-exome sequencing (WES) significantly improves the diagnosis of the etiology of fetal structural anomalies. This study aims to evaluate the diagnostic value of prenatal WES and to investigate the pathogenic variants in structurally abnormal fetuses. METHODS: We recruited 144 fetuses with structural anomalies between 14 and 2020 and 15 December 2021 in the study. Genetic screening was performed by WES combined with karyotyping and chromosomal microarray analysis. The molecular diagnostic yield of prenatal WES for each type of fetal structural anomaly and the identified pathogenic genes and mutations were reported. RESULTS: In this study, we retrospectively analyzed the clinical and genetic data of 145 structurally anomalous fetuses. These cases were classified into 9 phenotypic classes based on antenatal ultrasound findings. Thirty-eight pathogenic variants in 24 genes were identified in 35 of the 145 cases, including 14 novel variants in 13 genes (EP300, MYH3, TSC2, MMP9, CPLANE1, INVS, COL1A1, EYA1, TTC21B, MKS1, COL11A2, PDHA1 and L1CAM). Five additional pathogenic variants were classified as incidental findings. Our study showed that the overall diagnosis rate of WES was 28.1% (27/96) in the parent-fetus trio cases and 16.3% (8/49) in the proband-only cases. Fetuses with musculoskeletal anomalies had the highest diagnostic yield (51.4%, 19/37). In addition, FGFR3 and COL1A1 were the most common pathogenic genes. CONCLUSIONS: Our work expands the mutation spectrum of the genes associated with fetal structural anomalies and provides valuable information for future parental genetic counselling and pregnancy management of the structurally anomalous fetuses.

Annulation of α-bromocinnamaldehydes to access 3-formyl-imidazo[1,2-α]pyridines and pyrimidines under transition metal-free conditions.

An environmentally friendly and transition metal-free method for the annulation of α-bromocinnamaldehydes was established. 3-Formyl-imidazo[1,2-α]pyridines and pyrimidines were obtained in moderate to excellent yields. This approach features easily available starting materials, transition metal-free conditions, good functional group tolerance and operational simplicity.

Base-promoted highly efficient synthesis of nitrile-substituted cyclopropanes via Michael-initiated ring closure.

A convenient and efficient annulation reaction has been developed for the general synthesis of dinitrile-substituted cyclopropanes in moderate to excellent yields. A variety of 2-arylacetonitriles and α-bromoennitriles were compatible under the standard conditions. The reaction was achieved through tandem Michael-type addition followed by intramolecular cyclization. The preliminary application of this method was confirmed by the synthesis of the 2,4-dioxo-3-azabicyclo[3.1.0]hexane scaffold.

Iron(III)-catalyzed α-cyanation and carbonylation with 2-pyridylacetonitrile: divergent synthesis of α-amino nitriles and tetrahydroisoquinolinones.

Iron-catalyzed oxidative synthesis of N-aryl-substituted tetrahydroisoquinolines (THIQs) toward tetrahydroisoquinoline-based derivatives is reported. A wide range of α-amino nitriles and tetrahydroisoquinolinones are synthesized in moderate to good yields. This approach involves a new organic nitrile source, a cheap iron catalyst under an oxygen atmosphere, and temperature-controlled divergent synthesis and features complete selectivity and operational simplicity.