Letters in Organic Chemistry - Volume 4, Issue 2, 2007

A new type of Salen ligands derived from (2R, 3R)-N-benzyl-2,3-diaminopyrrolidine and aromatic hydroxyaldehydes was synthesized and tested in the enantioselective alkylation of aromatic aldehydes with diethylzinc, moderate selectivity being observed. This study represents the application of a new type of Zn- Salen ligands and opens the way to exploring these promising new structures in other enantioselective and biological processes.

A new synthetic approach to 3-aryl isoquinolines, based on the Pd-catalyzed Suzuki cross-coupling reaction, is reported. The described procedure represents an efficient method to prepare 3-aryl isoquinolines by reaction of a preformed 3-chloro isoquinoline with a phenylboronic acid, especially when the nitrogen atom is positively charged.

Treatment of the commercially available 3-methoxyphenylacetonitrile (6) with sodium bis (trimethylsilyl)amide and subsequent cyclobisalkylation with α,ω-dibromo or dichloroalkanes in THF at 0 °C produces adducts 7a-d, which serve as precursors to the new conformationally constrained phenylalkylamides 5a-h. Compounds 5a-f are melatonin receptor agonists in the Xenopus laevis melanophore assay and their potency depends on both the size of the R group and the size and shape of the β-substituent. The fact that the cyclohexano-substituted analogs 5g and 5h are, regardless of the size of the R group, melatonin receptor antagonists, implies that the nature of the β-substituent constitutes a functional probe in the receptor's dynamic agonist-antagonist conformational equilibrium.

Here, we report the C-terminal scaffold assembly of triple helical collagen mimetics using a triserine lactone (TSL) scaffold. It was found that the TSL scaffold can promote the triple helix formation and enhance the thermal stability of the resulting collagen-like structures.

The three-component Ugi reactions of 3,4-dihydroisoquinolines, isocyanides and acids furnished 2- acyl-N-substituted-1,2,3,4-tetrahydroisoquinoline-1-carboxamides in moderate to good yields. Chiral, nonracemic acids induced only poor diastereoselectivities in the condensations. Hydrolysis of the Ugi carboxamides gave the corresponding 1,2,3,4-tetrahydroisoquinoline-1-carboxylic acids, which due to their ready ability to undergo racemization, were obtained as racemic mixtures or with low enantiomeric excesses.

Secondary phosphine chalcogenides add to benzoylacetylene in KOH-THF suspension (the addition proceeds solely to the triple bond) to form depending on the PH-addend nature and reaction conditions either α,β- or β,β-diadducts, regardless of reactant ratio.

Anion binding properties of triindolylmethane was investigated by 1H NMR spectroscopy in CDCl3. Triindolylmethane selectively binds chloride anion over other anions tested. This selectivity will be attributed to the proper size of the binding pocket for chloride anion and the formation of the multiple hydrogen bonds between three indole NHs and chloride anion.

Thio-Claisen rearrangement of symmetrically substituted 1,4-but-2-ynes (3a,b and 4) exhibit tandem cyclization and afforded compounds 5a,b and 6 in good yields. These sulphides 3a,b and 4 were in turn prepared from commercially available thiophene. The key step in this transformation is tandem [3,3] sigmatropic rearrangement.

The first efficient synthesis of enantiopure homoketopinic acid, an interesting camphor derivative is firstly reported. The synthetic procedure uses 10-(triflyloxy)camphor as key electrophilic intermediate. The ability of 10-(triflyloxy)camphor to react selectively with a charged C-nucleophile (cyanide anion) without undergoing Grob fragmentation of the norbornane framework is also demonstrated.

A novel one-pot asymmetric reductive amination of 3-methoxyacetophenone with (S)- or (R)-α- methylbenzylamine using the combination of Ti(OiPr)4/Raney-Ni/H2 has been reported. This procedure provides excellent yield and diastereomeric excess. After cleaving the chiral auxiliary, (S)- or (R)-1-(3- methoxyphenyl)ethylamine was obtained in high yield.

Three-component aza-Diels-Alder reactions of Danishefsky's diene with aldehydes and amines took place smoothly to afford dihydro-4-pyridones with high yields in the presence of a catalytic amount of silica sulfuric acid (SSA). This new protocol consistently has the advantages of operational simplicity, economic consideration, and high yield.

A number of thieno [3,2-b] pyrimidines are regioselectively synthesized in good yields from 5-(4- aryloxybut-2-ynylthio) via sulfoxide rearrangement/tandem cyclization protocol by the treatment of the sulfides with one equivalent of m-CPBA in chloroform at 0-5°C with stirring the reaction mixture at room temperature for 2 h.

Fifteen new 3-[(4-hydroxy-6-methly-2(1H)-pyridinones)-3-yl]-4-substituted- (1H)-1,2,4-triazole-5- thione compounds were synthesized from methyl 4-hydroxy-6- methyl-2-oxo-1,2-dihydropyridine-3- carboxylate in good overall yields by four step reactions. Molecular structure of these compounds was confirmed by IR, NMR, MS, elemental analysis and X-ray diffraction. Their antitumor activities were evaluated in vitro by the SRB and MTT methods. The results show that there are two compounds which are highly effective against KB cells and one compound which is highly effective against Bel-7402 cells.

Concise and effective synthesis of alkyl tetrasaccharides were achieved from the key intermediates alkyl 2,3,4-tri-benzoyl-β-D-glucopyranoside (5) and 2,3,4,6-tetra-O-benzoyl-β-D-glucopyranosyl-(1→3)- [2,3,4,6-tetra-O-benzoyl-β-D-glucopyranosyl-(1→6)]-2,4-di-O-acetyl-α-D-glucopyranosyl trichloroacetimidate (6), followed by deacylation. Bioassay of the inhibition of S180 noumenal tumors showed that alkyl tetrasaccharides could be employed as potential agent for cancer treatment.

New methods have been developed for the functionalization of the non-aromatic C ring of morphinans with Suzuki-Miyaura cross-coupling of sulfonates and bromides.