PhD Scientific Days 2026

Poster Session 2.G - Pharmaceutical Sciences and Health Technologies

Synthesis and unambiguous assignment of absolute configurations for bacillamide B–D and neobacillamide A alkaloids, and their antipodes

Name of the presenter

Pollák, Patrik

Institute/workplace of the presenter

Egis Pharmaceuticals Plc.

Authors

Patrik Pollák¹
1: Egis Pharmaceuticals Plc.

Text of the abstract

The increasing frequency of algal blooms in aquatic ecosystems has intensified interest in bacillamide alkaloids due to their notable algicidal properties.[1,2] During a critical review of the literature, we identified several inconsistencies and contradictory reports concerning the absolute configuration and the optical rotation of both naturally isolated and synthetically prepared bacillamides.
To resolve these issues, we developed a new enantioselective synthesis of bacillamides B–D, neobacillamide A, and their antipodes, starting from the respective enantiomers of 2-(1-hydroxy)ethyl-thiazole. This synthetic route enables the efficient and stereocontrolled preparation of all target compounds, including their antipodes.
Crucially, single-crystal X-ray diffraction (XRD) analysis of the picrate salt of (–)-bacillamide D provided an unambiguous assignment of its absolute configuration. Using this result as a stereochemical reference point, we reliably determined the absolute configurations and directions of optical rotation for the entire series of synthesized bacillamides and their enantiomers. Chiral HPLC methods has also been developed to confirm the enantiomeric excess (ee) for all alkaloids and their enantiomers.
Our findings correct earlier misassignments in the literature and provide a definitive structure–chirality–optical rotation correlation for this class of bioactive natural products. The clarified stereochemical data are essential for a deeper understanding of structure–activity relationships and for the future design of analogues with enhanced biological efficacy.

References:
[1] Wang, B.; Tao, Y.; Liu, Q.; Liu, N.; Jin, Z.; Xu, X. Mar. Drugs 2017, 15, 247.
[2] Wang, Y.; Liu, Q.; Wei, Z.; Liu, N.; Li, Y.; Li, D.; Jin, Z.; Xu, X. Sci. Rep. 2018, 8, 8555.