Moroidin

Moroidin, a bicyclic octapeptide, has been isolated from Dendrocnide moroides (also called Laportea moroides) and Celosia argentea. The structure of moroidin was confirmed in 2004 by X-ray crystallography. It contains two unusual crosslinks, one between leucine and tryptophan and the other between tryptophan and histidine. These linkages are also present in an analogous family of compounds, the celogentins. ==Total synthesis==

The total synthesis of moroidin has not yet been described. Partial syntheses including the Leu-Trp and Trp-His linkages have been achieved. In their total synthesis of celogentin C, Castle and coworkers first obtained the Leu-Trp cross-link. The formation of this bond involved an intermolecular Knoevenagel condensation followed by radical conjugate addition and nitro reduction. This gave a product mixture of diastereomers, with the major product having the desired configuration. Chen and coworkers demonstrated another stereoselective approach, which coupled iodotryptophan to 8-aminoquinoline by palladium catalysis to give a single diastereomer with the desired Leu-Trp linkage and configuration. The Trp-His cross-link is addressed by Castle and coworkers, who used oxidative coupling by NCS to form the C-N linkage. To prevent over-chlorination, NCS was incubated with Pro-OBn, which reacts with NCS so as to modulate its concentration. This method of cross-linking tryptophan and histidine was used in subsequent total synthesis efforts. ==Toxicity==

Stinging toxin Moroidin is one of several biologically active compounds isolated from the venom of Dendrocnide moroides, a member of the stinging nettle family. The plant stores its venom in silica hairs that break off when touched, delivering the toxins through the skin and inducing extreme pain. Moroidin also produces a similar pain response when injected subdermally, so it is thought to be partially responsible for the plant’s toxicity. However, moroidin injections are not as potent as injections of crude matter isolated from Dendrocnide moroides, suggesting that there are additional stinging toxins in the venom. Anti-mitotic agent Moroidin has shown to have anti-mitotic properties, chiefly by inhibiting the polymerization of tubulin. Tubulin protein polymers are the major component of microtubules. During mitosis, microtubules form the organizing structure called the mitotic apparatus, which captures, aligns, and separates chromosomes. The proper alignment and separation of chromosomes is critical to ensure that cells divide their genetic material equally between daughter cells. Failure to attach chromosomes to the mitotic apparatus activates the mitotic checkpoint, preventing cells from entering anaphase to proceed with cell division. Agents that disrupt microtubules therefore inhibit mitosis through activation of this checkpoint. Moroidin and its related compounds, the celogentins, inhibit tubulin polymerization. Of this family, celogentin C is the most potent (IC50 0.8×10−6 M), and it is more potent than the anti-mitotic agent vinblastine (IC50 3.0×10−6). Moroidin has the same potency as vinblastine. Because of this biological activity, compounds in this family have potential as anti-cancer agents. ==References==