Total Synthesis and Pharmacological Evaluation of Phochrodines A–C
The first syntheses of the <i>Phomopsis</i>-isolated natural products phochrodines A-C are reported. Functional group manipulations on a key 5<i>H</i>-chromeno[4,3-<i>b</i>]pyridine intermediate, itself synthesized from intramolecular Suzuki-Miyaura coupling, enabled facile and high-yielding syntheses of all three natural products. Additionally, sufficient material was generated to enable detailed pharmacological profiling of each compound. Preliminary drug metabolism and pharmacokinetic (DMPK) experiments and ancillary pharmacology screening revealed phochrodine C (<b>3</b>) as an attractive scaffold for further modification, particularly for medicinal chemists working in the antidepressant space.
Authors
- Aaron M. Bender (ORCID: https://orcid.org/0000-0003-0432-1648)
- Darren W. Engers (ORCID: https://orcid.org/0000-0002-3633-3072)
- Jacob L. Bouchard (ORCID: https://orcid.org/0000-0002-5936-1244)
- Krishnan Srinivasan
- Craig W. Lindsley (ORCID: https://orcid.org/0000-0003-0168-1445)
- Nathan D. Schley (ORCID: https://orcid.org/0000-0002-1539-6031)
- Olivier G. Boutaud (ORCID: https://orcid.org/0000-0002-8910-0598)
- Julie L. Engers (ORCID: https://orcid.org/0009-0004-3654-5464)
- Christopher C. Presley (ORCID: https://orcid.org/0000-0002-4641-4597)
- Sichen Chang
Institutions
- Vanderbilt University (US)
- Center for Discovery (US)
Publication Details
- Journal
- Journal of Natural Products
- Published
- 2025-04-01
- DOI
- https://doi.org/10.1021/acs.jnatprod.5c00104
- Citations
- 1
- Primary Topic
- Biological and pharmacological studies of plants
- Type
- article
- Field-Weighted Citation Impact
- 1.39