Synthesis of small cyclic peptides constrained with 3-(3-aminomethylphenyl)propionic acid linkers using free radical-mediated macrocyclization

In this letter, we report that small peptides (di- and tri-) having a 3-bromobenzyl group at the C-termini and an acryloyl group at the N-termini undergo an efficient Bu₃SnH-AIBN mediated intramolecular free radical cyclization to afford cyclic peptides in good yields. We also propose that these cyclizations are occurring via a pre-organized acyclic structure dictated by a reverse turn (γ/β-turn).     

Synthesis and conformation of Gly-Gly dipeptides constrained with phenylalanine-like aminocaproic acid linkers

[structure: see text] The constraint of dipeptides with linkers derived from 6-aminocaproic acid (Aca) is a useful means of constructing a beta-turn peptidomimetic. The extension of this concept to the mimicry of a tripeptide entails the incorporation of a side chain moiety on either end of the Aca chain. The synthesis and conformational analysis of two exemplary compounds is discussed.     

Synthesis and analytical properties of (S)-(+)-2-methoxy-2-(9-phenanthryl)propionic acid

2-Methoxy-2-(9-phenanthryl)propionic acid was synthesized as a novel chiral resolving agent. The absolute configuration of (+)-2-methoxy-2-(9-phenanthryl)propionic acid was determined to be S by using X-ray structural analysis of the (1R,2S,5R)-menthyl ester. In the crystal, the methoxyl and carbonyl groups of the ester are in a syn-periplanar position. The syn-periplanar conformations of (1R,2S,5R)-menthyl esters were also observed by the NMR analyses in CDCl₃. The utility of (S)-(+)-2-methoxy-2-(9-phenanthryl)propionic acid was exemplified by the resolution of (±)-3-octanol.     

Heterocyclic compounds from 3-(4-phenyl) benzoyl propionic acid

3-(4-Phenyl) benzoyl propionic acid was used as the starting material for the synthesisof furanones (2), pyrrolinones (5), pyridazinones (7), benzoxazinones (8) and quinazolinones (9-11). The behaviour of the derivatives of furanones and benzoxazinones toward different nucleophiles is reported.     

Synthesis of α-amino-β-(1-methyl-2-benzimidazolyl)propionic acid

Depending on the reaction conditions, reaction of 1-methyl-2-formylbenzimidazole with hydantoin gives an aldol or crotonoid condensation product. Alkaline hydrolysis of these products gives 1, 2-dimethylbenzimidazole. The dihydro derivative of the crotonoid condensation product can be hydrolyzed to -amino--(1-methyl-2-benzimidazolyl)-propionic acid.     

Synthesis of 1,3-diketones from 3-(4-R-phenyl)propionic acids

Self-acylation of 3-(4-R-phenyl)propionic acids (R = H, Br, 1-adamantyl) in trifluoroacetic anhydride catalyzed by trifluoromethanesulfonic acid provides a simple and efficient synthesis of 1,3-diketones. Indan-1-ones formed in the first step undergo acylation to give the corresponding 2-(3-phenyl-1-oxopropyl) indan-1-ones as the major products. One-pot synthesis of polysubstituted pyrazoles directly from 3-(4-R-phenyl)propionic acids is described.     

Synthesis and reactions of β-(5-halo-3-uracyl) propionic acids

The reaction of elementary bromine and iodine with -(3-uracyl)-propionic acid has given the corresponding -(5-bromo-3-uracyl) and -(5-iodo-3-uracyl)propionic acids. The methyl esters and amides of the acids have also been synthesized for the first time.     

Synthesis of 2-(5-hydroxymethyl-2-formylpyrrol-1-yl)propionic acid lactone

2-(5-Hydroxymethyl-2-formylpyrrol-1-yl)propionic acid lactone was synthesized in six steps with a 17.0% overall yield, starting from L-alanine. The synthetic route involved the Clauson-Kaas reaction, Vilsmeier reaction, and transesterification. The transesterification was the key step in the formation of the target compound.     

Synthesis and reactivity of 3-(trichlorogermyl)propanoic acid and 3-(triphenylgermyl) propanoic acid

3-(Trichlorogermyl)propanoic acid (la) reacts with phenylmagnesium bromide in malar ratio 1:4 to give 3-(triphenylgermyl)propanoic acid (2a).In the compounds la and 2a theβ-carboxylic functional group shows some unusual properties when they react with excess of phenylmagnesium bromide.The compound la reacts with phenylmagnesium bromide in molar ratio 1:5 to give phenyl 2-(triphenylgermyl)ethylketone (3a) and in molar ratio 1:6 to give l,l-diphenyl-3-(triphenylgermyl)propanol (4a).The compound 2a reacts with phenylmagnesium bromide in molar ratio 1:2 to give 3a and in molar ratio 1:3 to give 4a also.Dehydration of the compound 4a with dilute hydrochloric acid seems especially easy.Moreover,the compound la reacted with phenylmagnsium bromide in molar ratio 1:6,then the mixture was treated with dilute hydrochloric acid to give 1,1-diphenyl-3-(triphenylgermyl)-1-propene (5a) in one pot reaction.Alkyl Ge-C bond in the compound 5a can be cleaved selectively by lithium aluminium hydride ( LiAlH4) in good yiel     

Synthesis of 2-alkyl-2-(3-cyanopyridin-2-ylthio)propionic acids

Derivatives of 2-alkyl-2-mercaptopropionic acid were synthesized based on the substituted 3-cyanopyridin-2(1H)-thiones. The synthesis was carried out by the heating of a mixture of thione, alkyl methyl ketone, and chloroform in the presence of a base. The reaction proceeds readily for acetone, whereas alkyl methyl ketones require a prolonged heating in the presence of a phase-transfer catalyst. Methyl esters were prepared from the acids obtained. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 1967–1970, October, 2007.