Novel Fmoc-polyamino acids for solid-phase synthesis of defined polyamidoamines

A versatile solid-phase approach to sequence-defined polyamidoamines was developed. Four different Fmoc-polyamino acid building blocks were synthesized by selective protection of symmetrical oligoethylenimine precursors followed by introduction of a carboxylic acid handle using cyclic anhydrides and subsequent Fmoc-protection. The novel Fmoc-polyamino acids were used to construct polyamidoamines demonstrating complete compatibility to standard Fmoc reaction conditions. The straightforward synthesis of the building blocks and the high efficiency of the solid-phase coupling reactions allow the versatile synthesis of defined polycations.     

Novel orthogonal strategy toward solid-phase synthesis of 1,3,5-substituted triazines

[reaction: see text] To improve upon the previous orthogonal method for synthesis of a triazine library, an alternative strategy has been developed via oxidation-activation of the thioether to the sulfone. Through a comparison between these two methods, the sulfone strategy was demonstrated as an enhanced method in the generation of highly pure triazine library compounds.     

Novel approaches for the solid-phase synthesis of biheterocyclic dihydroimidazole analogues

The solid-phase syntheses of dihydroimidazolyl 2-alkylthiobenzimidazoles, dihydroimidazolyl 2-alkylsulfonylbenzimidazoles, dihydroimidazolyl dihydroquinoxalin-2,3-diones, and dihydroimidazolyl dihydrobenzimidazol-2-imines are described. Following reduction of a resin-bound amino acid amide, the primary amine of the resulting resin-bound diamine was N-acylated with 4-fluoro-3-nitrobenzoic acid. Treatment with POCl3 led to formation of a dihydroimidazole derivative via dehydrative cyclization. The resin-bound dihydroimidazole derivative was then used as the key starting material for the synthesis of the aforementioned biheterocycles. Following cleavage, the resulting compounds, obtained in moderate yield and good purity, were characterized by LC-MS and 1H NMR and 13C NMR spectroscopy.     

An efficient solid-phase synthesis of 3-substituted and 3,3-disubstituted 1,2-dialkylpyrazolidine-3,5-diones

An efficient and regioselective procedure for the synthesis of di-, tri- and fully-substituted pyrazolidine-3,5-diones on a solid-phase format is described. Microwave irradiation provided significant rate enhancement in this protocol. To demonstrate the versatility of this chemistry, a representative set of 25 compounds was prepared.     

Efficient solid-phase synthesis of a library of imidazo[1,2-a]pyridine-8-carboxamides

A versatile method for the solid-phase synthesis of imidazo[1,2-a]pyridine-based derivatives, imidazo[1,2-a]pyridine-8-carboxamides, has been developed. They were obtained by treatment of the amino group of the polymer-bound 2-aminonicotinate with different alpha-haloketones, followed by halogenation at the 3-position of the polymer-bound imidazo[1,2-a]pyridine. The derived polymer-bound imidazo[1,2-a]pyridines 5, 6, and 7 were finally cleaved from the solid-support with an excess of primary or secondary amines. The final crude products were purified from excess amines by solid-supported liquid-liquid extraction (SLE).     

Continuous-flow solid-phase peptide synthesis

We describe a simple manually operated synthesizer for solid-phase peptide synthesis (SPPS). The synthesis is performed on standard polystyrene-based resin in a flow reactor under low-pressure conditions. The usefulness of the present configuration of SPPS is exemplified on the synthesis of two octapeptide and one decapeptide amides.     

Microwave-assisted solid-phase synthesis of peptoids

Microwave irradiation reduces the reaction time for the solid-phase synthesis of peptoids. Under these conditions, coupling of each residue requires only 1 min. The purity and yields of peptoids synthesized in this way are as good as or better than those achieved using standard methods. [reaction: see text]     

Efficient solid-phase synthesis of sulfahydantoins

A novel solid-phase strategy allows the efficient preparation of "traceless" sulfahydantoins. A total of 28 derivatives, with crude purity generally higher than 85%, were prepared by parallel synthesis. Through reductive alkylations, Mitsunobu reactions, and sulfamoylation reactions on oxime resin, the synthetic strategy affords sulfahydantoin derivatives selectively substituted at N(2), N(5) and N(2), N(5) positions, although yields of disubstituted compounds are lower. The mild reaction conditions involved lead to sulfahydantoins without racemization.     

Microwave-assisted solid-phase synthesis of phthalimides

[reaction: see text] A traceless solid-phase synthesis of substituted phthalimides is proposed. The target compounds are obtained within minutes by a microwave-assisted cyclative cleavage in good yields and excellent purities.     

Versatile solid-phase synthesis of s-arylisothioureas

Resin-bound amines 4a-m condense with di(benzotriazol-1-yl)methanimine 6 to give 1H-benzotriazole-1-carboximidamide resins 7a-m, which subsequently react with thiols 9a'-g' followed by cleavage affording nonprotected isothioureas 1aa'-mg' in high yields and with good purities. Analogous reactions with secondary amines activated with EtMgBr lead to guanidines 2a,b,e-g in moderate yields. Resin-bound isothioureas 1 are converted by acyl chlorides or carboxylic acids into acyl derivatives 12a-n in high yields and with good purities.     

Novel proton acceptor immonium-type coupling reagents: application in solution and solid-phase peptide synthesis

A novel proton acceptor coupling reagent shows superiority to those described previously. The oxygen in the carbocation moiety confers more solubility to the reagent. Furthermore, it enhances coupling yields and decreases racemization, allowing the use of 1 equiv of base.     

Novel route to the synthesis of chalcogenolanes, chalcogenanes, and 1,2-dichalcogenaepanes*

The saturated heterocyclic compounds C₄H₈Y, C₅H₁₀Y, and C₅H₁₀Y₂ (Y = Se or Te) have been prepared by the reaction of 1,4-dibromobutane or 1,5-dibromopentane with potassium chalcogenides. The novelty of the route consists of the use of the hydrazine hydrate–KOH system for the reductive generation of potassium selenide, telluride, diselenide or ditelluride from elemental chalcogens.     

Rapid microwave-assisted solid-phase glycopeptide synthesis

Coupling of glycosylated Fmoc-Thr or Fmoc-Ser with N-terminal amino acids on a resin proceeded smoothly under microwave irradiation for 20 min with much higher efficiency (98% yield per coupling) than found in more general conditions. Compared with a conventional protocol, the present method greatly reduces the time required for solid-phase glycopeptide synthesis from 4 days to 7 h, as is the case with the synthesis of Muc-1-related 20-residue glycopeptide carrying five core-2 trisaccharide chains. [structure: see text]     

The synthesis of 1,2-diacetyl- and 1,2-diethylferrocenes

A method is described for the preparation of 1,2-diacetylferrocene, in which ferrocene is acetylated with acetyl chloride in the presence of AlCl₃ in methylene chloride. Addition of the ferrocene to an excess of the acetylation mixture over a prolonged period was found to be most favourable. The 1,2-diacetylferrocene formed proved to be free of the 1,3-isomer. It was reduced with LiAlH₄/AlCl₃ to 1,2-diethylferrocene.     

Stereoselective synthesis of 1,2-diamino-1,2-diarylethane derivatives

A procedure was developed for selective opening of the cis-2,4,5-triarylimidazoline ring to form erythro-1,2-diamino-1,2-diarylethane derivatives. These ring-opening products, erythro-ethylenediamine derivatives, can undergo quantitative isomerization to threo-ethylenediamine derivatives in the presence of strong bases in DMSO.__________Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 206–209, January, 2005.     

One-pot synthesis of rac-1,2-diphenylethylene-1,2-diamine

Russian Chemical Bulletin -