Letters in Organic Chemistry - Volume 4, Issue 3, 2007

Modifications at the largely unexplored C14 position of the baccatin III core of the taxanes were carried out. Oxidation at C14 of 7-TES-13-ketobaccatin III with benzeneseleninic anhydride resulted in novel A, B ring rearranged products. A probable mechanism for product formation and reductive transformations of the rearranged products are described.

Chiral oxazoline cyanocuprates were prepared and added to conjugated nitroalkenes. Stereoselectivity up to 80% was achieved with the cuprate prepared from the chiral oxazoline derived from (S)- Phenylalaninol.

A novel family of chiral ammonium-based ionic liquids containing a chiral moiety and a free hydroxyl function has been designed and synthesized from isosorbide. The synthesis of these ionic liquids is easy and practical owing to the commercially available starting materials. These new chiral ionic liquids can be used as chiral reaction media as well as catalysts in asymmetric synthesis, which are currently being investigated in our laboratory.

Dihydroxyethylene containing compounds, envisaged as aspartic protease inhibitors (cores), were easily synthesized in few steps, by a sequence involving ring opening of diacetyl tartaric anhydride, peptide coupling and de-esterification under basic conditions affording the desired diols in a simple and inexpensive method.

We have developed three new chiral 3-substituted BINOL Schiff base ligands for the asymmetric diethylzinc addition to aldehydes in the presence of titanium tetraisopropoxide. The reaction provided optically active second alcohols in high yield and moderate enantioselectivity (up to 67% ee).

The first polystyrene-supported chiral picolyl menthol has been prepared via a selective hydrosilylation route and evaluated for asymmetric catalysis. The new catalyst was efficient and reusable in the test reaction of diethylzinc addition to benzaldehyde at room temperature. The enantioselectivity was comparable with that of the soluble counterpart.

The CuCl-catalyzed reaction of (1-bromo-2-propenyl)trimethylsilane with silyl enol ethers or ketene silyl acetals in a CH3CN solution was studied. A new method for the preparation of ketone and ester derivatives bearing a vinylsilane functionality at the γ-position was developed.

The synthesis of a new push-pull fluorophore containing phosphane sulfide derivative was realized via organophosphorous reaction and Sonogashira cross-coupling reaction. This molecule exhibits high fluorescence quantum yields and large Stokes shift in polar solvents.

Some steroidal phosphorothioate, phosphoroselenoate, and phosphate derivatives conjugated with 3'-Azido-3'-deoxythymidine (AZT) have been synthesized in good yields and their structures were confirmed on the basis of spectral methods. The result has shown that some of bioconjugates possess activity against breast cancer MCF-7 in bioassay.

The reaction of lithium acetylenide ((R-C°CLi, where R = Ph, Pent, Bu) with 1,1,1-trihalo-4-alcoxy- 3-alken-2-ones [CX3C(O)C(R2)=C(R1)-OR3, where X = Cl, F; R1, R2 = H, Me; R3 = Me, Et] in the presence of BF3·Et2O to give 1,4- or 1,2-addition products is reported. The regiospecific formation of 1,4-addition products was observed for substrates with R1 = H, and for substrates which had the methyl group on C-4 (R1 = Me), the formation of 1,2-addition products was favored.

New 1,5-Dihydro-4-(3,4,5-trimethoxyphenyl)-3H-furo[3,4-b]carbazol-3-ones were synthesized via a key Diels-Alder reaction under microwave irradiation. Two routes were investigated to generate the dienoic precursors. Both started from 3-formylindole, which was used in a six steps synthesis to obtain the complex heterocycle. The use and removal of indolic protective groups such as t-Boc and benzenesulfonyl have been studied. The Diels- Alder reaction generating the carbazole ring was optimised under either thermal conditions or microwave irradiation.

In this work we present a convenient synthetic route to novel 5,6,7-substituted 3-phenyl-6,7-dihydroisoxazolo[ 4,5-d]pyrimidines. The key synthetic step is based on the cyclization of 4-amino-3- phenylisoxazole-5-carboxamides and ethyl 4-[(ethoxymethylene)amino]-3-phenylisoxazole-5-carboxylates. The developed methodology can be easily adapted to high-throughput combinatorial format.

Organophosphorus nerve agents such as sarin, cyclosarin or tabun are substances originally developed for military purposes. These compounds are able to inhibit an enzyme acetylcholinesterase (AChE; EC 3.1.1.7) via phosphorylation in its active site. AChE reactivators and anticholinergics are generally used as antidotes in the case of intoxication with these agents. In this work, reactivation potency of twenty-one structurally different AChE reactivators was tested in vitro and subsequently, relationship between their chemical structure and biological activity was described. Cyclosarin as an appropriate member of the nerve agents family was chosen to illustrate these relationships.

A nanoclay-catalyzed atom and energy-efficient low hazardous tandem conjugate additioncyclodehydration of cyclic thioureas (ethylenethiourea and 2-mercaptoimidazole/-benzimidazole) with dielectrophiles (chalcones) readily annulates a 1,3-thiazine ring on imidazoles to yield 7H-imidazo[2,1-b]-1,3- thiazines under solvent-free microwave irradiation in a one-pot procedure.

Synthesis of several spiro[4-aryl-5-hydroxy-2-(1-isoquinolinyl)-5-phenyl-4,5-dihydro-3H-pyrrole- 3,3'-3H-chroman-4'-ones] has been accomplished in satisfying yields by regioselective [4+2] cycloaddition reaction of a 2-benzoyl-1,2-dihydroisoquinoline-1-carbonitrile tetrafluoroborate salt across (E)-3-arylidene-4- chromanones. The spirocompounds evolve to pyrroles after acidic hydrolysis. The crystal structure of (10c) has been determined by an X-Ray study diffraction.