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. 2025 Apr 25;88(4):996-1003.
doi: 10.1021/acs.jnatprod.5c00104. Epub 2025 Apr 1.

Total Synthesis and Pharmacological Evaluation of Phochrodines A-C

Jacob L Bouchard  1   2 , Sichen Chang  1   2 , Srinivasan Krishnan  1   2 , Christopher C Presley  1   2 , Olivier Boutaud  1   2 , Nathan D Schley  3 , Darren W Engers  1   2 , Julie L Engers  1   2 , Craig W Lindsley  1   2   3   4 , Aaron M Bender  1   2
Affiliations

Total Synthesis and Pharmacological Evaluation of Phochrodines A-C

Jacob L Bouchard et al. J Nat Prod. .

Abstract

The first syntheses of the Phomopsis-isolated natural products phochrodines A-C are reported. Functional group manipulations on a key 5H-chromeno[4,3-b]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 (3) as an attractive scaffold for further modification, particularly for medicinal chemists working in the antidepressant space.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
(A) Representation of Phomopsis and (B) chemical structures of phochrodines A–D (1–4). Artwork is courtesy of Paige Poppe.
Figure 2
Figure 2
Retrosynthetic strategy to access common 5H-chromeno[4,3-b]pyridine intermediate 5.
Scheme 1
Scheme 1. Synthesis of Suzuki–Miyaura Precursor 7
Scheme 2
Scheme 2. Synthesis of Phochrodines A–C (1–3)
See this image and copyright information in PMC

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