Synthesis of tetrahydro- 1H-β-carbolines via ultrasound one-pot Ugi- azide/Pictet–Spengler process

The β-carboline are a group of natural and synthetic indole alkaloids that contain a common tricyclic pyrido[3,4-b]indole ring in their structure. The saturated members are known as tetrahydro-β-carboline (TH-β-Cs) and they are well documented for their biological properties. Natural or synthetic derivatives of TH-β-Cs are privileged molecules because they are present in a wide variety of bioactive compounds and some commercial drugs. On the other hand, 1,5-disubstituted-tetrazoles (1,5-DS-T) are a privileged heterocyclic bioisosteres of the cis-amide bond in peptides by mimicking their structure, polarity, and hydrogen donor/bond sites. The Ugi azide (UA) consists in a four-component condensation of amines, aldehydes, trimethylsilyl azide as hydrazoic acid precursor and isocyanides.

UA is the most efficient methodology for the synthesis of 1,5-DS-T. The combination with post- transformation reactions, for example Pictet Spengler (P-S) allows to increase molecular complexity and diversity of final products. The strategy UA/P-S reaction has been exploited for the construction of complex nitrogen heterocycles , however commonly it involves prolonged reaction times and is carried out at elevated temperatures. Herein we developed the one-pot synthesis of tetrahydro-1H-b-carbolines via the UA)/(P-S) strategy, under mild reaction conditions. The complex product contains two privileged heterocyclic: 1,5-disubstituted-1H-tetrazole and tetrahydro- β-carboline that may find application in medicinal chemistry.