Mimicry of peptide backbone geometry and heteroatomic side-chain functionality: synthesis of enantiopure indolizidin-2-one amino acids possessing alcohol, acid, and azide functional groups

Indolizidinone amino acids possessing various heteroatomic side chains at their 5- and 7-positions have been synthesized through modification of hydroxymethyl indolizidinone amino acids 5 and 6. Displacements of the methanesulfonates from alcohols 5 and 6 with sodium azide, as well as oxidation of alcohol 5, have been used to furnish orthogonally protected indolizidin-2-one diamino carboxylates 7 and 8, and indolizidin-2-one amino dicarboxylate 9. Both 5- and 7-hydroxymethylindolizidinone amino acids 5 and 6 were obtained from sequences commencing with the Claisen condensation of alpha-tert-butyl gamma-methyl l-N-(PhF)-L-glutamate to furnish di-tert-butyl 4-carbomethoxy-5-oxo-2,8-di-[N-(PhF)amino]azelate 10 (PhF = 9-(9-phenylfluorenyl)). Subsequent hydride reduction of 10 to an isomeric mixture of diols 12, selective protection of the primary alcohol as tert-butyldimethylsilyl ether 14 and oxidation of the secondary alcohol gave di-tert-butyl 4-tert-butyldimethylsilyloxymethyl-5-oxo-2,8-di-[N-(PhF)amino]azelate 15 as a separable diastereomeric mixture. Linear ketone 15 and alcohol 14 were then converted to the indolizidinone heterocycles by routes featuring reductive aminations, methanesulfonate displacements, and lactam cyclizations. A series of rigid scaffolds designed to mimic the conformations of dipeptides possessing serine, lysine, and glutamate residues has thus been synthesized by this new route for installing heteroatomic side-chain functional groups onto the indolizidin-2-one system.     

Mimics of peptide turn backbone and side-chain geometry by a general approach for modifying azabicyclo[5.3.0]alkanone amino acids

Peptide mimics with constrained backbone and side-chain geometry are important tools for studying structure activity relationships of biologically active candidates. A general method for creating β-turn mimics possessing side-chain diversity has been developed featuring diastereoselective S(N)1 displacements of an iodide precursor. In particular, 6-iodo-pyrroloazepin-2-one amino ester 10 has served as a common precursor in reactions with a variety of alcohol, phenol, nitrate, and azide nucleophiles to provide an array of constrained peptide mimics.     

Synthesis of 3-acetylbicyclo[3.1.0]-2-hexen-4-one

Conclusions The synthesis of 3-acetylbicyclo[3.1.0]-2-hexen-4-one was accomplished.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 10, pp. 2350–2352, October, 1972.     

Synthesis of 2-Methylbenzanthreno[2,3-d]imidazol-7-one

The synthesis of the benzanthrone based heterocyclic compound 2-methylbenzanthreno[2,3-d]imidazol-7-one has been achieved. It shows a strong luminescence intensity in the yellow-green region of the spectrum.     

Synthesis of unnatural amino acids: spiro[4.5]-2-aza-decan-3-carboxylic acid

Spiro[4.n]-2-aza-alkan-carboxylic acids represent bulky proline analogues with increased lipophilicity. They are readily available from cyclic nitriles via alkylation with bromoacetaldehyde acetals, reduction to the corresponding amine, cyclisation to the imine and subsequent Strecker synthesis.     

Condensed as-triazines. Synthesis of 7-aryl-8H-[1,4]thiazino[2,3-e]-1,2,4-triazin-3(2H)-one

Ring closure of 6-amino-3-oxo-as-triazine-5-thione with α-haloketones provides the thiazino[2,3-e]-1,2,4-triazines which dehydrate via an unusual pathway to give 7-aryl-8H[1,4]thiazino[2,3-e]-1,2,4-triazin-3(2H)-ones.     

A New and Simple Synthesis of 3H-Benzo[f]chromen-3-one and 2H-Benzo[h]chromen-2-one Derivatives

Summary.  Protonation of the highly reactive 1:1-intermediate produced in the reaction between triphenylphosphine and dimethyl acetylenedicarboxylate by naphthols lead to vinyl triphenylphosphonium salts which undergo an aromatic electrophilic substitution reaction with the conjugated base to produce the title compounds. Received August 14, 2001. Accepted November 22, 2001     

Synthesis of enantiopure 3-azabicyclo[3.3.0]octen-7-one derivatives via intramolecular Pauson-Khand cycloaddition reaction using tri-O-acetyl-D-glucal as starting material

Some N-substituted-3-azabicyclo[3.3.0]octen-7-one derivatives have been synthesized in an enantiomerically pure form starting from tri-O-acetyl-D-glucal via intramolecular Pauson-Khand (IPK) cycloaddition.     

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.     

Synthesis of 2-Phenyl-3-oxa-5-azatricyclo[4.4.0.02 , 7]decan-4-one

Cleavage of the lactone ring in 7-phenylbicyclo[3.1.1]heptan-6,7-carbolactone by the action of ammonia and hydrazine and subsequent oxidative cyclization of the resulting hydroxy amide and hydroxy hydrazide gave a cyclic carbamate, 3-oxa-5-azatricyclo[4.4.0.0^{2 , 7}]decan-4-one.     

Synthesis of 7-(4-piperidyl)- [1,6]naphthyridin-5-one and 3-(4-piperidyl)isoqunolin-1-one

7-(4-Piperidyl)[1,6]napththiridin-5-one was synthesized on the basis of 2-methylnicotinic acid. 3-(4-Piperidyl)isoquinolin-1-one was synthesized from the diethylamide of o-toluic acid and Weinreb's amide of N-Boc-isonipecotic acid.     

Synthesis of 4-substituted 3-oxabicyclo[3.1.0]hexan-2-one

Cyclopropanedicarboxylic acid anhydride can be converted to 4-substituted 3-oxabicyclo-[3.1.0]hexan-2-one by reaction with Grignard reagents in ether or tetrahydrofuran solution.     

Synthesis and Properties of 3-Thia-9-azabicyclo[3.3.1]nonan-7-one

N-Benzyl-3-thia-9-aza-bicyclo[3.3.1]nonan-7-one has been prepared from methyl 4-bromocrotonate by reaction sequence involving sodium sulfide, benzylamine, and Dieckmann condensation. Some spectral and chemical properties of this system are also reported.     

Synthesis of 4,7,9-trimethyl-2H-thieno[3,2-g]-1-benzopyran-2-one. A psoralen isostere

The title compound, an isostere of 4,5′,8-trimethylpsoralen, was prepared in good yield from 7-[(2-bromo-allyl)thio]-4,8-dimethylcoumarin via a thio-Claisen rearrangement. The structure of the final product was determined by proton nmr decoupling experiments.     

Synthesis and mesomorphic properties of 7-alkoxybezopyrano[2,3-c]pyrazol-3-one

A new series of fused polyheterocyclic aromatic compounds, 7-alkoxybezopyrano[2,3-c]pyrazol-3-one (C- n BPP), were synthesised and characterised by infrared, ¹H-nuclear magnetic resonance (NMR), ¹³C-NMR and two-dimensional ¹H-¹³C cosy spectra. Their phase transition behaviour was investigated by differential scanning calorimetry and polarising optical microscopy. All of these compounds showed enantiotropic mesophases with temperature domains of 12–60°C and 22–69°C on heating and cooling processes for a carbon number of the alkoxy chain from 2 to 10. The effect of the length of the alkoxy chain on the mesomorphic properties was discussed. Comparison of C- n BPP and several kinds of coumarin derivatives indicated that the intermolecular hydrogen bonding acted as the driving force of the mesophase formation.     

Tricyclo[7.2.1.02,7]dodec-2(7)-en-12-one. Synthesis and Some Reactions

Tricyclo[7.2.1.02,7]dodec-2(7)-en-12-one was synthesized by dehydration of the corresponding hydroxy ketone and was brought into the Leuckart reaction. The resulting N-tricyclo[7.2.1.0^2,7]dodec-2(7)-en- 12-ylformamide was hydrolyzed to 12-aminotricyclo[7.2.1.02,7]dodec-2(7)-ene and was converted into 2,7-epoxy derivative. The structure of the latter was determined by X-ray analysis. Hydrolysis of the amide group gave 12-amino-2,7-epoxytricyclo[7.2.1.02,7]dodecane. The stereochemistry of hydroamination of the bridging carbonyl group is discussed.     

Intramolecular [2 + 2] photocycloaddition of alkenes incorporated in a carbohydrate template. Synthesis of enantiopure bicyclo[3.2.0]heptanes and -[6.3.0]undecanes

Intramolecular [2 + 2] photocycloaddition of alkenes with a furano sugar placed between them have been investigated under both copper(I)-catalyzed and sensitized conditions. The copper(I)-catalyzed photocycloaddition of the dienes 4a, 4b, and 4c led to unexpected formation of the thermodynamically less stable cis-syn-cis 4-5-5 tricyclic adducts 5a, 5b, and 5c, respectively. The sensitized photocycloaddition of the diene 14 also gave the cis-syn-cis adduct 15 showing that the copper(I) catalyst does not have any influence on the stereochemical course through coordination with the anomeric ring oxygen of the furano sugar. The identical stereochemical course observed under both catalyzed and sensitized photoaddition reactions have been attributed to be of steric origin. Bis(dienes) 25a and 25b, which gave an intractable mixture on copper(I)-catalyzed irradiation, underwent smooth photocycloaddition in the presence of benzophenone, and the resulting 1,2-divinyl cyclobutanes underwent spontaneous [3.3]-rearrangement at room temperature to produce bicyclo[6.3.0]undecanes 30a and 30b, respectively. This investigation provides an approach for the construction of enantiopure bicyclo[3.2.0]heptanes and -[6.3.0]undecanes.