Electrochemical Annulation of Indole-Tethered Alkynes Enabling Synthesis of Exocyclic Alkenyl Tetrahydrocarbazoles.

An electrochemical sulfonylation-triggered cyclization reaction of indole-tethered terminal alkynes with sulfinates as sulfonyl sources has been developed, which affords exocyclic alkenyl tetrahydrocarbazoles in good chemical yields. This reaction features convenient operation and tolerates a wide scope of substrates with a variety of electronically and sterically diverse substituents. Furthermore, high E-stereoselectivity is observed for this reaction, which provides an efficient method for the preparation of functionalized tetrahydrocarbazole derivatives.

Arylsulfonylation-Triggered Cyclization of 3-Alkenyl Indoles Enabling Synthesis of Tetrahydro-γ-carboline.

A visible-light promoted cyclization reaction of 3-alkenyl indole derivatives with arylsulfonyl chlorides as coupling partners has been developed, which afforded functionalized tetrahydro-γ-carbolines in good chemical yields. The reaction used 3-alkenyl indoles as radical acceptors and proceeded via the sequence of sulfonylation and intramolecular cyclization. The reaction was carried out under mild conditions and tolerated a wide range of substrates, which provides an efficient strategy for the synthesis of tetrahydro-γ-carboline derivatives.

New pharmaceuticals approved by FDA in 2020: Small-molecule drugs derived from amino acids and related compounds.

Amino acids (AAs) play an important role in the modern health industry as key synthetic precursors for pharmaceuticals, biomaterials, biosensors, and drug delivery systems. Currently, over 30% of small-molecule drugs contain residues of tailor-made AAs or derived from them amino-alcohols and di-amines. In this review article, we profile 12 AA-derived new pharmaceuticals approved by the FDA in 2020. These newly introduced drugs include Tazverik (epithelioid sarcoma), Gemtesa (overactive bladder), Zeposia (multiple sclerosis), Byfavo (induction and maintenance of procedural sedation), Cu 64 dotatate, and Gallium 68 PSMA-11 (both PET imaging), Rimegepant (acute migraine), Zepzelca (lung cancer), Remdesivir (COVID-19), Amisulpride (nausea and vomiting), Setmelanotide (obesity), and Lonafarnib (progeria syndrome). For each compound, we describe the spectrum of biological activity, medicinal chemistry discovery, and synthetic preparation.

Visible-Light-Irradiated Cascade Reaction of Indole-Tethered Alkenes to Access Tetracyclic Tetrahydro-γ-carbolines.

A series of indole-derived alkenes have been designed and applied in a photocatalytic cascade reaction with bromodifluoroacetate esters, affording an unknown type of tetracyclic tetrahydro-γ-carboline derivative in up to 90% yields. Mechanistic studies suggest that the reaction proceeds with tetrahydro-γ-carboline as a key intermediate. The reaction tolerates a diverse pool of substrates, which provides an efficient method for the construction of tetracyclic tetrahydro-γ-carboline compounds.