Abstract
Molecular libraries of natural product-like and structurally diverse compounds are attractive in early drug discovery campaigns. In here, we present synthetic methodology for library production of hexahydropyrrolo[2,1-a]isoquinoline (HPIQ) compounds. Two advanced HPIQ intermediates, both incorporating two handles for diversification, were synthesized through an oxidative cleavage/Pictet–Spengler reaction sequence in high overall yields. A subsequent metal-catalyzed cross coupling/amidation protocol was developed and its utility in library synthesis was validated by construction of a 20-membered natural product-like molecular library in good overall yields.
Original language | English |
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Journal | Bioorganic & Medicinal Chemistry |
Volume | 23 |
Issue number | 11 |
Pages (from-to) | 2646-2649 |
Number of pages | 4 |
ISSN | 0968-0896 |
DOIs | |
Publication status | Published - 2015 |
Keywords
- Drug discovery
- Molecular libraries
- Heterocycles
- Pictet–Spengler
- Molecular diversity