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A concise and direct synthetic strategy for the construction of benzo[a]carbazole-5-carboxylates has been disclosed via the Diels–Alder reaction of arynes and 3-alkenylindoles. The reaction is highly selective and affords the benzo[a]carbazole-5-carboxylates in good-to-excellent yields.

Background Bardet‐Biedl syndrome (BBS) is an autosomal recessive pleiotropic disorder of the primary cilia that leads to severe visual loss in the teenage years. Approximately 80% of BBS cases are explained by mutations in one of the 21 identified genes. Documented causative mutation types include missense, nonsense, copy number variation (CNV), frameshift deletions or insertions, and splicing variants. Methods Whole genome sequencing was performed on a patient affected with BBS for whom no mutations were identified using clinically approved genetic testing of the known genes. Analysis of the WGS was done using internal protocols and publicly available algorithms. The phenotype was defined by retrospective chart review. Results We document a female affected with BBS carrying the most common BBS1 mutation (BBS1: Met390Arg) on the maternal allele and an insertion of a ~1.7‐kb retrotransposon in exon 13 on the paternal allele. This retrotransposon insertion was not automatically annotated by the standard variant calling protocols used. This novel variant was identified by visual inspection of the alignment file followed by specific genome analysis with an available algorithm for transposable elements. Conclusion This report documents a novel mutation type associated with BBS and highlights the importance of systematically performing transposon detection analysis on WGS data of unsolved cases.

The direct assembly of benzo[c]carbazole derivatives via the Diels–Alder reaction of arynes and easily accessible 2-alkenylidoles was reported. By employing different aryne precursor loads, 6,7-dihydrobenzo[c]carbazoles or aryl-substituted 7,11b-dihydrobenzo[c]carbazoles could be controllably generated in good to excellent yields under a nitrogen atmosphere. On the other hand, when the reaction was conducted under oxygen, oxidated/aromatized product benzo[c]carbazoles could be generated directly with high selectivity and efficiency in a one-step manner. Interestingly, the benzo[c]carbazole-5-carboxamide amidation derivatives of the above products showed good antitumor activities. The inhibitory effect of these molecules against cancer cells was also described.

A concise and direct synthetic strategy for the construction of benzo[a]carbazole-5-carboxylates has been disclosed via the Diels–Alder reaction of arynes and 3-alkenylindoles. The reaction is highly selective and affords the benzo[a]carbazole-5-carboxylates in good-to-excellent yields.

Depending on the fluorinating reagent the reaction of arynes with aziridines affords fluorinated β-amino acid esters or unexpected spiro-derivatives.

Phenanthridines are prepared from various O-acetyloximes and in situ generated arynes through a C-H bond activation/insertion/cyclization/elimination sequence.