ABSTRACT
A novel approach to the production of chiral 1,3-cyclohexadienals has been developed. The organocatalysed asymmetric reaction of different ß-disubstituted-α,ß-unsaturated aldehydes with a chiral α,ß-unsaturated aldehyde in the presence of a Jørgensen-Hayashi organocatalyst provides easy and stereocontrolled access to the cyclohexadienal backbone. This method allows for the synthesis of potential photoprotective chiral 1,3-cyclohexadienals and extra extended conjugation compounds in a simple manner.
Subject(s)
Aldehydes/chemistry , Cyclohexenes/chemical synthesis , Carbon-13 Magnetic Resonance Spectroscopy , Crystallography, X-Ray , Cyclohexenes/chemistry , Models, Molecular , Proton Magnetic Resonance Spectroscopy , Spectrometry, Mass, Electrospray Ionization , StereoisomerismABSTRACT
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.
Subject(s)
4-Butyrolactone/analogs & derivatives , Sesterterpenes/chemistry , Sesterterpenes/chemical synthesis , 4-Butyrolactone/chemical synthesis , 4-Butyrolactone/chemistry , 4-Butyrolactone/pharmacology , Cell Line, Tumor , Cellular Reprogramming Techniques , Chemistry Techniques, Synthetic , Humans , Sesterterpenes/pharmacology , StereoisomerismABSTRACT
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.
Subject(s)
Sesquiterpenes/chemical synthesis , Silicon/chemistry , Cyclization , Molecular Structure , Sesquiterpenes/chemistry , StereoisomerismABSTRACT
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.
Subject(s)
4-Butyrolactone/analogs & derivatives , Antineoplastic Agents/chemical synthesis , Furans/chemical synthesis , Neoplasms/drug therapy , Sesterterpenes/chemical synthesis , 4-Butyrolactone/chemical synthesis , 4-Butyrolactone/chemistry , 4-Butyrolactone/pharmacology , Animals , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Australia , Cell Line, Tumor , Cell Proliferation/drug effects , Diterpenes/chemistry , Furans/chemistry , Furans/pharmacology , Humans , Indicators and Reagents/chemistry , Molecular Conformation , Molecular Structure , Neoplasms/pathology , Osmolar Concentration , Pacific Ocean , Porifera/chemistry , Sesterterpenes/chemistry , Sesterterpenes/pharmacology , StereoisomerismABSTRACT
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.
