Model studies for the synthesis of the antibiotic lactonamycin and the discovery of new reactions and mechanisms for the construction of substituted heterocycles

A new and highly efficient route for the construction of a model for the synthesis of lactonamycin 1 is reported. The chemistry has been utilised for the synthesis of heterocyclic rings, and new reactions for the synthesis of dienes and alkynes are reported.     

Facile and stereo-controlled synthesis of 2-deoxynojirimycin, Miglustat and Miglitol

A novel and facile synthesis of a series of the biologically significant iminosugar derivatives including 2-deoxynojirimycin, Miglustat and Miglitol is reported. The synthesis features a strategic double inversion mechanism for securing the desired stereochemistry at C5 position of such glucose-type carbohydrate mimetics, representing a practical and remarkable improvement on the previously reported method that suffers from the loss of the stereo-control during the reaction process.     

Multicomponent macrocyclization reactions (MCMRs) employing highly reactive acyl ketene and nitrile oxide intermediates

An efficient synthesis of spiro-fused macrolactams by a multicomponent macrocyclization reaction (MCMR) is reported. The use of highly reactive, transient intermediates in this MCMR permits short reaction times, even at high dilution. The methods employed for this MCMR were first developed as a four-component strategy for the synthesis of β-ketoamide isoxazolines and a new macrocyclization reaction is reported.     

Synthesis and Characterization of Some Thallium Cyclopentadienide Fused Ring Pyridazines

Thallium cyclopentadiene (Cp) salts are important precursors for the synthesis of a variety of compounds having materials and commercial applications. The synthesis of 5,6-fused ring thallium Cp pyridazines 2a–d from previously reported 5,6-fused ring pyridazines is described herein. This route was quite general, and features an efficient and convenient two-step synthesis of a series of TlCp salts in a THF solution of thallium ethoxide. Full characterization of newly formed TlCp salts 3a–d are reported.     

Asymmetric synthesis of both the enantiomers of antidepressant venlafaxine and its analogues

Chemoenzymatic asymmetric synthesis of antidepressant agent venlafaxine and its analogue have been reported in this communication. The main highlight of the reported synthesis is the stereoselective synthesis of cyanohydrins by (S)-hydroxynitrile lyase (Hevea brasiliensis) followed by lipase catalyzed kinetic resolution.     

Total synthesis and reassignment of stereochemistry of obyanamide

The total synthesis of a marine cytotoxic cyclic depsipeptide obyanamide is reported. The synthesis has led to a reassignment of the C-3 configuration in β-amino acid residue. And this revision is also supported by biological test.     

Synthesis and fluorescent properties of a new photostable thiol reagent “BACM”

The 3-maleimidocoumarin BACM ( 2d ) is a new tag designed to react with thiols in biological materials to form fluorescent derivatives whose emission is in the 500 nm (green) region with good resistance to fading. The fluorescence properties of its N-acetyl-L-cysteine derivative are described. BACM itself is non-fluorescent, as is its predecessor, DACM ( 1a ). A synthesis of BACM is reported which avoids the formation of nitrocoumarin isomers obtained in the reported synthesis of DACM. The synthesis of the related 3-(4-maleimidophenyl)coumarin is also described.     

Synthesis and absolute configuration of cordiaquinone K, antifungal and larvicidal meroterpenoid isolated from the Panamanian plant, Cordia curassavica

Total synthesis of cordiaquinone K, a new antifungal and larvicidal meroterpenoid, is reported. The absolute configuration of cordiaquinone K was confirmed by the synthesis.     

Efficient metathesis route to the B-ring of eleutherobin and other medium-sized cyclic ethers

A short and efficient RCM route is reported for the synthesis of the B-ring of eleutherobin and other medium-sized cyclic ethers from readily available 1,2,5,6-diisopropylidene-d-glucose. This strategy is successfully extended to the synthesis of a few bicyclic ethers, which may find applications in the synthesis of novel bicyclic nucleosides.     

Synthesis of mono- and 1,4-dicarbonyl compounds based on the oxygenation of phosphonate carbanions. Synthesis of dihydrojasmone,allethrone and methylenomycin b

Oxidation of the α-alkylthio-substituted phosphonate carbanions was found to give the corresponding carbonyl compounds. A new synthesis of 1,4-dicarbonyl systems involving the oxygenation of phosphonate carbanions as a key step is described. Total synthesis of dihydrojasmone and allethrone and formal synthesis of methylenomycin B is reported.     

Synthesis of the western half of breviones C, D, F and G

The enantioselective synthesis of the diterpenic moiety in the abeo-breviano skeleton is reported. The synthesis is carried out starting from 2-methyl-1,3-cyclohexanedione and EVK in eleven steps following a ring-expansion strategy once the tricyclic perhydrophenantrene skeleton has been obtained. A new Tiffeneau-Demjanov rearrangement under dark conditions is reported in which the insertion of the new methylene group is directed towards the most hindered side of the carbonyl group. This result is new and opposite to those reported in the literature under light (filtered or un-filtered wavelengths) conditions where insertion in the less hindered side is usually preferred.     

Stereoselective synthesis of (-)-cephalotaxine and C-7 alkylated analogues

A total asymmetric synthesis of (-)-cephalotaxine is reported. The chemistry of alpha,beta-unsaturated gamma-lactams was used to access the 1-azaspiro[4.4]nonane skeleton in enantiomerically pure form via a stereocontrolled semipinacolic rearrangement of an alpha-hydroxyiminium ion. This spiro compound was transformed into (-)-cephalotaxine without any racemization or epimerization by following the racemic synthesis reported by Kuehne. We thus performed a total synthesis of (-)-cephalotaxine in 98.7% ee with an overall yield of 9.8% over a 16 steps sequence. This synthetic process was adaptable to the access of some alkylated analogues.     

A convergent Pd-catalyzed asymmetric allylic alkylation of dl- and meso-divinylethylene carbonate: enantioselective synthesis of (+)-australine hydrochloride and formal synthesis of isoaltholactone

The use of a mixture of dl- and meso-divinylethylene carbonate as an electrophile in palladium-catalyzed asymmetric allylic alkylation reactions is reported. From the diastereomeric mixture of meso and chiral racemic starting materials, a single product is obtained in high optical purity employing either oxygen or nitrogen nucleophiles. The resulting dienes have proven to be versatile synthetic intermediates as each carbon is functionalized for further transformation and differentiated by virtue of the reaction. A mechanism for this intriguing transformation is proposed and a concise enantioselective total synthesis of (+)-australine hydrochloride is reported as well as a formal synthesis of isoaltholactone.     

First total synthesis of (±)-floribundane B: An approach based on Johnson-Claisen rearrangement of a Morita-Baylis-Hillman adduct

The first total synthesis of (±)-floribundane B is reported. Johnson-Claisen rearrangement of a Morita-Baylis-Hillman adduct assembled all of the stereochemical features of this secoiridoid. The formal synthesis of (±)-oleocanthal and the synthesis of a chemical constituent of olive press juice is also reported.     

The total synthesis and reassignment of stereochemistry of dragonamide

The first total synthesis of dragonamide is reported. The synthesis has led to a reassignment of the configuration at the stereogenic centre on the alkyne-bearing fragment of the molecule.     

Oligo- and poly-nucleotides: 50 years of chemical synthesis

It is fifty years since the first chemical synthesis of a dinucleoside phosphate and a dinucleotide with natural 3'-->5'-internucleotide linkages was reported. The main developments in the methodology of oligo- and poly-nucleotide synthesis that have taken place since are described.     

Synthesis of Oligodeoxynucleotides by the Phosphite-Triester Method Using Dimer Units and Different Phosphorous-Protecting Groups

A simple synthesis of phosphoamidite dinucleotides with two different phosphorous-protecting groups and their use for the synthesis of 2′-oligodeoxynucleotides on a polymer support is reported.     

The first total synthesis of the natural product angoluvarin

The total synthesis of angoluvarin, a member of the dihydrochalcone family of natural products, is reported. Starting with 2-bromophenol, the synthesis was accomplished in eight steps with an overall yield of 2%. This represents the first reported synthesis of angoluvarin.     

A direct route to triazole boronic esters and their application in the synthesis of small molecule arrays

Alkynylboronates represent useful substrates for the direct synthesis of triazole boronic esters by their thermal cycloaddition with azides. A telescoped cycloaddition-cross-coupling protocol is reported and its employment in the synthesis of a small triazole array is disclosed.     

Highly regio- and stereocontrolled synthesis of β-substituted α-tributylstannyl enamides

The regio- and stereocontrolled synthesis of β-substituted α-stannyl enamides is reported starting from internal ynamides. The synthesis of new ynamides as well as bis-ynamides is also described. Finally first examples of successful cross-coupling to afford α/β-disubstituted enamides are also reported.