Ring-closing metathesis as key step in the synthesis of Luffarin I, 16-epi-Luffarin I and Luffarin A.

Natural sesterterpenolides, luffarin I and luffarin A, from Luffariella geometrica have been synthesized, and this is the first reported synthesis of luffarin A. The Yamaguchi esterification of the nor-diterpenic fragment, obtained from 2.8-15µM, with the appropriate furane alcohols yielded the necessary diene intermediates for the synthesis of the target molecules. The key strategic step in this synthesis was the ring-closing metathesis (RCM) reaction of the diene intermediates. This strategy allowed for the synthesis of 16-epi-luffarin I and analogues for structure-activity relationship (SAR) studies. The most active compound exhibited antiproliferative activity against a panel of six human solid tumour cell lines with [Formula: see text] values in the range 2.8-15 M.

Synthesis of Luffarin L and 16-epi-Luffarin L Using a Temporary Silicon-Tethered Ring-Closing Metathesis Reaction.

The first synthesis of luffarin L (1) and 16-epi-luffarin L (2) by a silicon-tethered ring closing metathesis as a key step has been achieved. The stereochemistry and absolute configuration of the natural sesterterpenolide luffarin L (1) and a new route for the stereoselective synthesis of sesterterpenolides with a luffarane skeleton have been established.

Synthesis and bioactivity of Luffarin I.

The first synthesis of Luffarin I, sesterterpenolide isolated from sponge Luffariella geometrica, has been accomplished from commercially available sclareol. The key strategy involved in this synthesis is the diastereoselective reduction of an intermediate ketone. Luffarin I against human solid tumor cell lines showed antiproliferative activities (GI50) in the range 12-17 µM.

Biomimetic synthesis of two salmahyrtisanes: salmahyrtisol A and hippospongide A.

Sesterterpenes with a salmahyrtisane skeleton have been synthesized for the first time. (-)-Sclareol has been selected as a precursor for the synthesis of two novel natural products: salmahyrtisol A (1) and hippospongide A (2). Our results represent a biomimetic approach to obtaining salmahyrtisanes from hyrtiosanes. Salmahyrtisol A has shown an activity comparable to that of the standard anticancer drugs in the cell lines A549, HBL-100, HeLa, and SW1573.

Synthesis of Bioconjugate Sesterterpenoids with Phospholipids and Polyunsaturated Fatty Acids.

A series of sesterterpenoid bioconjugates with phospholipids and polyunsaturated fatty acids (PUFAs) have been synthesized for biological activity testing as antiproliferative agents in several cancer cell lines. Different substitution analogues of the original lipidic ether edelfosine (1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine) are obtained varying the sesterterpenoid in position 1 or 2 of the glycerol or a phosphocholine or PUFA unit in position 3. Simple bioconjugates of sesterterpenoids and eicosapentaenoic acid (EPA) have been obtained too. All synthetic derivatives were tested against the human tumour cell lines HeLa (cervix) and MCF-7 (breast). Some compounds showed good IC50 (0.3 and 0.2 µM) values against these cell lines.

Synthesis and biological activity of polyalthenol and pentacyclindole analogues.

A series of indole sesquiterpenes analogues of polyalthenol and pentacyclindole have been synthesized starting from ent-halimic acid in order to test their biological activity. These analogues include diverse oxidation levels at the sesquiterpenyl moiety and different functionalization on the indole ring. All synthetic derivatives were tested against a representative panel of Gram positive and Gram negative bacterial strains, and the human solid tumour cell lines A549 (non-small cell lung), HBL-100 (breast), HeLa (cervix), SW1573 (non-small cell lung), T-47D (breast) and WiDr (colon). Overall, the compounds presented activity against the cancer cell lines. The resulting lead, displaying a polyalthenol scaffold, showed GI50 values in the range 1.2-5.7 µM against all cell lines tested.

Sesquiterpenyl indoles.

The natural product sesquiterpenyl indoles are structural hybrids from farnesyl pyrophosphate and tryptophan or its precursors, often with unusual and complex structural features, many of them with interesting biological activities. In this review the compounds of this class known until now are classified, a biosynthetic approach of each group is proposed and a review of the synthesis or synthetic approaches is communicated.

Yamaguchi-type lactonization as a key step in the synthesis of marine metabolites: (+)-luffalactone.

A Yamaguchi-type cyclization of 5 and subsequent photochemical oxidation of the furanic ring are the key steps in the first synthesis of the marine metabolite (+)-luffalactone 4 and its epimer at C-16, 16-epi-luffalactone, 27. With this work, we have successfully established the absolute configuration of the natural product. The key intermediate 5 was obtained from the easily accessible diacetate 6a/6b.

Synthesis of an ent-halimanolide from ent-halimic acid.

An efficient synthesis of ent-halimanolide 2 (15,16-epoxy-12-oxo-ent-halima- 5(10),13(16),14-trien-18,2beta-olide), from ent-halimic acid has been achieved, corroborating the structure of the natural compound and establishing its absolute configuration.

Synthetic studies towards the ent-labdane diterpenoids: rearrangement of ent-halimanes.

For the first time ent-labdanes have been synthetised starting from ent-halimic acid, following a route that is the reverse of the biosynthetic one leading to the former compounds.

Synthesis of (R)-2-(benzyloxy)-tetrahydro-5,5-dimethylfuran by a new oxidative rearrangement.

The rearrangement under oxidative conditions of 3-(benzyloxy)-tetrahydro- 2,6,6-trimethyl-2H-pyran-2-carbaldehydes to afford a chiral protected tetrahydrofuran lactol is described.