Convenient synthesis of furan-3-carboxylic acid and derivatives

A convenient synthesis of furan-3-carboxylic acid and derivatives from aromatization of 4-trichloroacetyl-2,3-dihydrofuran followed by nucleophilic displacement of the trichloromethyl group by hydroxide, alcohols, and amines, is presented.     

An efficient route to all stereoisomeric enantiopure 6-amino-3-alkyl-3- azabicyclo[3.2.1]octane-6-carboxylic acids

A single-step synthesis on a gram scale of four pure stereoisomers of the 6-amino-3-azabicyclo[3.2.1]octane-6-carboxylic acid was carried out using (R)-1-phenylethylamine to confer chirality. The phenylethyl group, and the p-methoxy group linked to the N-atom, are easily removed by hydrogenolysis to afford the corresponding NH-3 derivatives. A series of N-3-alkyl compounds were prepared by way of a "one-pot" deprotection-alkylation procedure starting from the above key compounds. Their biological activity has been evaluated on the GABA receptor.     

A novel synthesis of 3-cyanoindoles and a new route to indole-3-carboxylic acid derivatives

2-Alkyl-3-cyanoindoles are obtained when 1-alkylmethyl-2-chloro-(or 2-phenylsulfonyl)-3-phenylsulfonylindoles are reacted with excess azide ion (90°/DMF). The reaction is considered to occur by a fragmentation recombination process in which the Schiff's base $\text{12}$ is of central importance. This proposal is supported by the formation of 2-substituted indole-3-carboxylates $\text{17}$ from aldehydes and the α-phenylsulfonyl-$\text{o}$-aminophenylacetic acid ester derivative $\text{16}$.     

Convenient synthetic route to an enantiomerically pure FMOC alpha-amino acid

A strategy for the facile alpha-amination of carboxylic acid menthyl esters is described. The resulting diastereomers, readily separable, can be individually carried on to each enantiomer of the FMOC alpha-amino acid. A variety of unnatural side chains were compatible with this approach. The menthyl ester was easily removed from the FMOC alpha-amino acid without racemization.     

Convenient route to enantiopure substituted butyrolactones: application in a formal synthesis of both enantiomers of enterolactone

A simple route for the synthesis of enantiopure substituted γ-butyrolactones involving a highly diastereoselective alkylation of an enantiomerically pure substituted latent succinate ester is described. This route provides entry into both enantiomers of 3,4-disubstituted butyrolactones from a single enantiomer, 2,3-di-O-cyclohexylidine-R-(+)-glyceraldehyde. The synthetic potential of this methodology has been demonstrated by a formal synthesis of both enantiomers of enterolactone.     

A novel route to enantiopure cyclopentene carboxylic acids based on 3-endo-bromocamphor

A novel four-step synthetic route to enantiopure cyclopentene carboxylic acids starting from commercially available 3-endo-bromocamphor is described. The synthesis is straightforward and practical. The key transformations involve firstly, an enantiospecific Wagner–Meerwein rearrangement of a bromocamphor derived cyanohydrin, and secondly the regiospecific C-(1)C-(2) bond scission of a 7-bromonorbornan-2-one.     

Convenient route to enantiopure aryl cyclopentanes via Diels-Alder reaction of asymmetric dienes. Total synthesis of (+)-herbertene and (+)-cuparene

A general route for the synthesis of highly substituted aryl cyclopentanes has been developed involving Diels-Alder reaction of asymmetric dienes prepared from (+)-camphoric acid followed by aromatization of the resulting cyclohexene derivatives. Employing this protocol enantiospecific synthesis of (+)-herbertene and (+)-cuparene has been accomplished.     

A practical synthetic route to enantiopure 6-substituted cis-decahydroquinolines

Starting from 4-substituted cyclohexanones, a practical synthetic route to enantiopure 6-substituted cis-decahydroquinolines has been developed, the key steps being a stereoselective cyclocondensation of an unsaturated δ-keto ester derivative with (R)-phenylglycinol and the stereoselective hydrogenation of the resulting tricyclic oxazoloquinolone lactams.     

A new highly efficient synthetic route to enantiopure 10-bromocamphor

A new enantiospecific synthetic route to the interesting chiral synthetic intermediate 10-bromocamphor starting from readily available camphor is described. The procedure takes place straightforwardly in only three synthetic steps with high overall yield. Mechanistically, two interesting enantiospecific Wagner–Meerwein rearrangements involving 2-norbornyl carbocations take place during the process.     

A new approach to 3-hydroxyquinoline-2-carboxylic acid

Quinoline-2-carboxylic acid derivatives cap the N-terminal of several natural cyclic peptides with antitumoral activity. A new and convenient route for the preparation of 3-hydroxyquinoline-2-carboxylic acid is discussed. The preparation of the title compound is accomplished by a four-step procedure from 3-hydroxyquinoline via MOM protection of the hydroxyl group, followed by a 1,2-addition of methyllithium to the quinoline ring with concomitant oxidation, and, finally, a two-step oxidation procedure for the transformation of the methyl group to the carboxylic acid along with removal of the MOM group. Furthermore, different attempts to its preparation led to other interesting quinolines, such as 2-chloro-3-hydroxyquinoline-4-carboxylic acid and a protected 3,3′-dihydroxy-2,2′-biquinoline.     

Convenient preparations of racemic and enantiopure methyl 6-oxopipecolate

Short, convenient syntheses of racemic and enantiopure methyl 6-oxopipecolate are described, starting from either pipecolic acid or (S)-lysine respectively. The sequence for the latter compound relies upon improved methodology for the oxidation of C-6 of lysine.     

Convenient synthesis of 3,4-methano-1,2,3, 4-tetrahydroisoquinoline-3-carboxylic acid and its derivatives as doubly constrained nonproteinogenic amino acid derivatives

Three strategies for the synthesis of the novel, doubly constrained, 3,4-methano-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid and its derivatives were evaluated. Only cyclocondensation of the mono(triphenyl)phosphonium salt derived from 1, 2-bis(bromomethyl)benzene with N-alkoxycarbonyloxamates in 1, 2-dimethoxyethane in the presence of potassium carbonate and subsequent cyclopropanation with dimethylsulfoxonium methylide in dimethyl sulfoxide furnished suitable O- and N-protected derivatives of 3,4-methano-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid in a convenient way. A detailed 2D DQF-COSY and 2D NOESY NMR analysis of the rotational isomerism of the latter bicyclic amino acid derivatives was performed. Various O- and N-protection protocols were worked out to afford access to a whole range of new derivatives of the title amino acid, suitable for peptide synthesis.     

Zirconocene-mediated route to enantiopure 9-oxabicyclononanes functionalized on both carbon bridges

[reaction: see text] A zirconocene-mediated ring contraction of 4-vinylfuranosides generated either from d-arabinose or d-glucose is followed by sequential oxidation to the ketone and alkynyl Grignard addition. The resulting cis-cyclobutanediols are subjected in turn to thermal rearrangement and intramolecular oxymercuration-demercuration. The regiochemistry of the final ring closure is controlled by the nature of R.     

The reaction of aromatic dialdehydes with enantiopure 1,2-diamines: an expeditious route to enantiopure tricyclic amidines

The condensation of enantiopure 1,2-diamines with terephthalaldehyde, isophthalaldehyde or 2-iodo-, 2-alkyl- or 2-aryl-1,3-benzenedialdehydes in toluene followed by treatment with NBS in dichloromethane gives direct access to enantiopure 1,4-, and 1,3-di(4,5-dihydro-1H-imidazol-2-yl)benzenes (diamidines). The condensation of o-phthalaldehyde, and other ortho-disubstituted aromatic dialdehydes, with enantiopure 1,2-diamines, without NBS, gives enantiopure 3,5-dihydro-2H-imidazol-[2,1]-isoindoles.     

Shortcut to fmoc-protected phosphinic pseudodipeptidic blocks

A three-component condensation reaction of Fmoc-carbamate, aldehydes, and alkylphosphinic acids provides a new, direct, and efficient method for synthesizing Fmoc-protected phosphinic pseudodipeptidic blocks, directly usable for solid-phase peptide synthesis. [reaction: see text]     

A facile synthesis of enantiopure 7-benzyloxycarbonyl-7-azabicyclo[2.2.1]heptane-2-carboxylic acid

An efficient procedure for the preparation of enantiopure 7-benzyloxycarbonyl-7-azabicyclo[2.2.1]heptane-2-carboxylic acids is described.     

Convenient route to super-expanded calixpyrroles: synthesis of Calix

meso-Alkylporphyrinogen-like cyclic oligomers containing furans and pyrroles have been synthesized by "3 + 2" and "4 + 2" approaches. Condensation of 5,5,10,10,15,15-hexaethyl-21, 22-dioxatetrapyrromethane with 2,5-bis[(alpha-hydroxy-alpha, alpha-dimethyl)furan] resulted in the formation of cyclic hexamer and cyclic dodcamer. Effects of catalysts, temperature, inorganic additives, solvent, and reaction concentration were examined.     

Convenient route to water-sensitive sol-gel precursors using click chemistry

The CuAAC-'click' reaction under anhydrous conditions is reported as a new tool for the preparation of moisture-sensitive triethoxysilyl compounds that are obtained in 5 minutes in excellent yield with simple purification.