# Tetracyclic Bis-Piperidine Alkaloids: Structures, Bioinspired Synthesis, Synthesis, and Bioactivities

## TL;DR

This paper reviews complex natural compounds from marine sponges that show promise as anticancer drugs but are difficult to synthesize.

## Contribution

The paper provides a comprehensive review of recent advances in synthesizing and understanding tetracyclic bis-piperidine alkaloids for cancer treatment.

## Key findings

- TcBPAs show antiproliferative effects on various cancer cell lines at low micromolar concentrations.
- The complex structure of TcBPAs makes their synthesis challenging, limiting further drug development.
- Recent progress in synthesis and biological evaluation highlights their potential in anticancer drug discovery.

## Abstract

Tetracyclic bis-piperidine alkaloids (TcBPAs) are structurally complex natural products primarily isolated from marine sponges of the order Haplosclerida. Distinguished by their intricate architecture, TcBPAs feature two central piperidine units linked by dual macrocyclic rings. These unique structural motifs contribute significantly to their biological activities. For example, TcBPAs exhibit antiproliferative activities at low micromolar concentrations across various cancer cell lines, including leukemia, melanoma, breast, colon, fibrosarcoma, and glioblastoma. Despite this promising therapeutic profile, the structural intricacy of TcBPAs has posed considerable challenges to the development of efficient synthetic methodologies, thereby limiting comprehensive exploration and potential clinical advancement. This review highlights recent progress and persisting challenges in the synthesis, structural analysis, and biological evaluation of TcBPAs, underscoring their therapeutic potential in anticancer drug discovery.