Synthesis of a hexahydropyrrolo indole (HPI) compound library

Expansion of chemical space for collaborative lead generation and drug discovery: the European Lead Factory Perspective

“…Indeed, a significant number of unprecedented spiro, bridged, and fused polycycles with different degrees of saturation, conjugation, and substitution have been synthesized and expanded to a library format. This has been recently exemplified by several publications from the ELF chemistry groups detailing the associated design and validation aspects [21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38]. Given that most theoretical ring systems remains unexplored [39], the synthesis of novel rings represents one of the strategies embraced by the ELF chemistry consortium to expand the available chemical space.…”

Oxazolidinones and 2,5-Dihydrofurans via Zinc-Catalyzed Regioselective Allenylation Reactions of l-α-Amino Aldehydes

“…The data recorded matched that previously reported. 25 (S)-tert-Butyl 3-(2-((tert-Butoxycarbonyl)amino)-3-oxopropyl)-1H-indole-1-carboxylate (2f). The title compound 2f was obtained following the same procedure used for 2b with tert-butyl 3-(2-((tertbutoxycarbonyl)amino)-3-methoxy-3-oxopropyl)-1H-indole-1-carboxylate S2 (0.11 g, 0.26 mmol) and diisobutylaluminum hydride (5.7 M in n-hexane, 0.10 mL, 0.57 mmol, 2.2 equiv) in toluene (1 mL).…”

“…The resulting allenic products are direct precursors to 2,5-dihydrofurans with a pendant N (25,Scheme 1b) and allenyloxazolidinones (23,Scheme 1b), which are two key heterocycles in a diverse array of biologically active structures, fragrance compounds, antirheumatics and antidiabetics. 10,11 Diastereoselective methods to prepare oxazolidinones with pendant unsaturated moieties are severely limited, 12 and while the preparation of 2,5-dihydrofurans by Au-catalyzed cyclisation of allenes is well known, the same method to 2,5-dihydrofurans with pendant N are unknown -the only other routes involve long non-general multi-step synthesis.…”