A new and general route to 2-pyrrolylglycine, 2-pyrrolylalanine and homo-2-pyrrolylalanine derivatives

Sarkar, Kaushik; Singha, Sovan K.; Chattopadhyay, Shital K.

doi:10.1016/j.tetasy.2009.06.021

Cited by 12 publications

(4 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Only a few studies that prepared the g-heterocyclic a-aminobutanoic acid have been performed [36][37][38][39][40][41][42][43][44][45][46][47] but are not effective for preparing our targeted amino acids. Looking at the successful example reported by Roth and Thomas [48], key intermediates 12-14 for our targeted analogs 10 and 11 were prepared from commonly and commercially available starting material as PEPTIDIC PLASMIN INHIBITORS POSSESSING NITRILE AS WARHEAD depicted in Scheme 1.…”

Section: Resultsmentioning

confidence: 99%

Synthesis and evaluation of tripeptidic plasmin inhibitors with nitrile as warhead

Teno

Otsubo

Gohda

et al. 2012

Journal of Peptide Science

View full text Add to dashboard Cite

Plasmin is best known as the key molecule in the fibrinolytic system, which is critical for clot lysis and can initiate matrix metalloproteinase (MMP) activation cascade. Along with MMP, plasmin is suggested to be involved in physiological processes that are linked to the risk of carcinoma formation. Plasmin inhibitors could be perceived as a promising new principle in the treatment of diseases triggered by plasmin. On the basis of the peptidic sequence derived from the synthetic plasmin substrate, a series of peptidic plasmin inhibitors possessing nitrile as warhead were prepared and evaluated for their inhibitory activities against plasmin and other serine proteases, plasma kallikrein and urokinase. The most potent peptidic inhibitors with the nitrile warhead exhibit the potency toward plasmin (IC(50) = 7.7-11 μM) and are characterized by their selectivity profile against plasma kallikrein and urokinase. The results and molecular modeling of the peptidic inhibitor complexed with plasmin reveal that the P2 residue makes favorable contacts with the open binding pocket comprising the S2 and S3 subsites of plasmin.

show abstract

Section: Resultsmentioning

confidence: 99%

Synthesis and evaluation of tripeptidic plasmin inhibitors with nitrile as warhead

Teno

Otsubo

Gohda

et al. 2012

Journal of Peptide Science

View full text Add to dashboard Cite

show abstract

“…Our synthesis started with the preparation of bishomoallylglycine derivative 11 ( Scheme 1 ) from the known aspartic acid derived aldehyde 4 [ 13 ]. The latter was converted to its doubly homologated derivative 8 through four conventional steps viz.…”

Section: Resultsmentioning

confidence: 99%

Synthesis of 2-aminosuberic acid derivatives as components of some histone deacetylase inhibiting cyclic tetrapeptides

Chattopadhyay

Sil

Mukherjee

2017

Beilstein J. Org. Chem.

View full text Add to dashboard Cite

A new synthesis of the important amino acid 2-aminosuberic acid from aspartic acid is reported. The methodology involves the alternate preparation of (S)-2-aminohept-6-enoate ester as a building block and its diversification through a cross-metathesis reaction to prepare the title compounds. The utility of the protocol is demonstrated through the preparation of three suberic acid derivatives of relevance to the design and the synthesis of peptides of biological relevance.

show abstract

“…Histidine analogs (i.e., thienylalanine, furylalanine, triazolylalanine, tetrazolylalanine, thiazolylalanine, imidazolylalanine, and pyrazolylalanine) have been used to study the importance of the hydrogen bond acceptor and donator properties of the imidazole side chain. − Components of naturally occurring peptides from marine organisms, amino acids bearing five-membered heterocycle side chains have been employed in peptidomimetics, macromolecular scafolds, and high-throughput synthesis . Although pyrrolylalanine ( 1 , Figure ) represents a promising histidine surrogate, few syntheses give an enantiopure product suitable for peptide chemistry. , For example, the natural pyrrolylalanine analog from the poisonous mushroom Clitocybe acromelalga , (2 S )-3-(2-carboxy-4-pyrrolyl)alanine ( 2 ), has been synthesized in protected form as a racemate and in optically active form from l -aspartic acid. − Enantiomerically pure (>94% ee) (2 S )- N -Cbz-3-(2-pyrrolyl)alanine derivatives were synthesized by enantioselective hydrogenation of the corresponding methyl and tert- butyl ( Z )-α,β-didehydroalaninates . (2 S )- N -(Boc)- N ′-Acetyl-3-(2-pyrrolyl)alanine was also synthesized from l -aspartic acid by a route featuring ring-closing metathesis and aromatization to form the heterocycle .…”

Section: Introductionmentioning

confidence: 99%

“…(2 S )- N -(Boc)- N ′-Acetyl-3-(2-pyrrolyl)alanine was also synthesized from l -aspartic acid by a route featuring ring-closing metathesis and aromatization to form the heterocycle . Prior to our preliminary research, to the best of our knowledge, , pyrrolylalanine has been used only once in the synthesis of a peptide analog. Racemic N -Cbz- N ′-(Boc)-3-(2-pyrrolyl)alanine was introduced into a thyrotropin-releasing hormone (TRH, pGlu-His-Pro-NHMe) analog to investigate the role of the histidine residue; however, no biological activity was reported…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Protected 2-Pyrrolylalanine for Peptide Chemistry and Examination of Its Influence on Prolyl Amide Isomer Equilibrium

Dörr

Lubell

2012

J. Org. Chem.

View full text Add to dashboard Cite

Protected enantiopure 2-pyrrolylalanine was synthesized for application in peptide science as an electron-rich arylalanine (histidine) analog with π-donor capability. (2S)-N-(Boc)-N'-(Phenylsulfonyl)-, (2S)-N,N'-bis-(phenylsulfonyl)-, and (2S)-N,N'-bis-(Boc)-3-(2-pyrrolyl)alanines (10, 3, and 14, respectively) were made in 13-17% overall yields and six to seven steps from oxazolidine β-methyl ester 4. Homoallylic ketone 5 was prepared by a copper-catalyzed cascade addition of vinylmagnesium bromide to ester 4 and converted to pyrrolyl amino alcohol 7 by olefin oxidation and Paal-Knorr condensation. Protecting group shuffle and oxidation of the primary alcohol enabled the synthesis of pyrrolylalanines. The bis-Boc analog 14 proved useful in peptide chemistry and was employed to make N-acetyl-pyrrolylalaninyl-proline N''-methylamide 25. A study of the influence of the pyrrole moiety on the prolyl amide isomer equilibrium of 25 using (1)H NMR spectroscopy in chloroform, DMSO, and water demonstrated that the pyrrolylalanine peptide exhibited behavior and conformations different from those of other arylalanine analogs.

show abstract

A new and general route to 2-pyrrolylglycine, 2-pyrrolylalanine and homo-2-pyrrolylalanine derivatives

Cited by 12 publications

References 60 publications

Synthesis and evaluation of tripeptidic plasmin inhibitors with nitrile as warhead

Synthesis and evaluation of tripeptidic plasmin inhibitors with nitrile as warhead

Synthesis of 2-aminosuberic acid derivatives as components of some histone deacetylase inhibiting cyclic tetrapeptides

Synthesis of Protected 2-Pyrrolylalanine for Peptide Chemistry and Examination of Its Influence on Prolyl Amide Isomer Equilibrium

Contact Info

Product

Resources

About