Marine natural products : synthesis and isolation of bioactive analogues [article]

Alban R. Pereira
2008
Tauramamide (2-12), a linear acylpentapeptide recently isolated from cultures of Brevibacillus laterosporus (PNG-276) collected in Papua New Guinea, was synthesized in 9 steps and 29% overall yield. Besides confirming the proposed structure, synthetic (2-12) allowed the antimicrobial assessment of this novel antibiotic. Additionally, a new analogue of the surfactin depsipeptides family named dealkylsurfactin (2-48), was prepared in 10 steps and 14% overall yield. The compound was employed as a
more » ... was employed as a biological tool in binding studies between the mitotic regulator isomerase Pinl and the microtubule-associated protein tau, a crucial interaction involved in Alzheimer's disease. Chemical exploration of Garveia annulata, a seasonal hydroid collected in Barkley Sound, British Columbia, led to the isolation of twelve secondary metabolites including four new compounds (3-53 to 3-56). Nine of these metabolites showed inhibition of indoleamine 2,3- dioxigenase (IDO), with the annulins among the most potent in vitro IDO inhibitors isolated to date. IDO plays a central role in immune escape, which prevents the immunological rejection of tumors or the allogeneic fetus. The ceratamine inspired antimitotic agent (4-142) and inactive analogue (4-157) were synthesized in no more than 8 steps, with overall yields of 20% and 15% respectively. Activity evaluation of these analogues suggested that potency improves with planarity and that the synthetically laborious imidazo[4,5,d]azepine core heterocycle of ceratamines is not required for activity. Haplosamate A (5-62), isolated from the marine sponge Dasychalina fragilis collected in Papua New Guinea, was found to be the first member of a new family of cannabinoid-active sterols. Saturation transfer double-difference (STDD) NMR experiments confirmed that (5-62)specifically binds the cannabinoid human receptors CB1 and CB2 via the classical cannabinoid pharmacophore. A growing appreciation of the therapeutic potential of PI3K inhibitors has encouraged the development of new inhibitory compo [...]
doi:10.14288/1.0061556 fatcat:5nd5epz3mje6reyilhqjz5wmyi