Abstract:
This thesis is an account of my investigation on the natural products deriving
from various marine algae and has resulted in the discovery of thirteen novel bioactive
metabolites. Isolation and characterization of these unique molecules were carried out
using different chromatographic techniques and by careful analyses of 1D and 2D NMR
data, respectively.
Two new thiazole-containing cyclic heptapeptides, cis,cis- and trans,trans-ceratospongamide,
were identified from an Indonesian red alga, Ceratodictyon
spongiosum Zanardini. These are a pair of stable conformers differing only in the
conformation of two proline amide bonds. The trans,trans-form was revealed to be a
potent anti-inflammatory agent in the inhibition of sPLA₂ expression in a cell-based
model.
The hermitamides are new malyngamide-type molecules isolated from a
collection of the marine cyanobacterium Lyngbya majuscula Gomont made in Papua
New Guinea. The semi-syntheses of these natural metabolites were achieved by
coupling the free-occurring C-14 lyngbic acid isolated from the microalga and the
commercially available aromatic amines. Two new semi-synthetic molecules, the N-methylated
derivatives of the hermitamides, were also prepared. The biological
properties of the hermitamides and synthetic derivatives were evaluated in several
bioassays.
The organic extract of another collection of L. majuscula Gomont from Papua
New Guinea was a prolific source of several novel cyclic depsipeptides, given the trivial
names clairamides A and B, wewakamide, carliamide, and guinamides A and B. These
molecules were characterized by having unique β-amino or β-hydroxy acid moieties,
one of which is being reported for the first time from the marine environment. The
absolute stereochemistry in clairamide A of one such unit, 2-methyl-3-amino-pentanoic
acid, is discussed. Clairamide B and carliamide exhibited moderate cytotoxic activities.
Investigation of another species of filamentous marine cyanobacterium, L.
bouillonii Hoffmann and Demoulin from Papua New Guinea yielded three novel
cytotoxic metabolites. These were two cyclic depsipeptides, bouillonamides A and B,
and a glycosidic macrolide, lyngbouilloside. The cytotoxic activities of these molecules
were evaluated in the neuro-2a mouse neuroblastoma cell assay. The isolation of these
metabolites demonstrated that L. bouillonii is a rich source of novel and biologically
active natural products.
