138108-37-9

Upstream product

• 3303-84-2 3-(tert-butyloxycarbonylamino)propionic acid 
• 100-51-6 benzyl alcohol 
• 99616-43-0 3-(benzyloxy)-3-oxopropan-1-aminium chloride 
• 1027977-74-7 C₁₃H₂₃NO₆ 
• 27019-47-2 β-alanine benzyl ester p-toluenesulfonate 
• 14529-00-1 benzyl 3-aminopropionate 

Downstream Products

• 108432-95-7 Boc-(β-Ala)4-OBzl 
• 138108-38-0 3-(3-Amino-propionylamino)-propionic acid benzyl ester 
• 144412-02-2 N-[N-[p-[N-(benzyloxycarbonyl)amidino]benzoyl]-β-alanyl]-β-alanine benzylester 
• 1027306-51-9 3-[3-(4-Carbamimidoyl-benzoylamino)-propionylamino]-propionic acid benzyl ester 
• 108432-94-6 Boc-β-Ala3-OBzl 

Relevant academic research and scientific papers

Mapping of the Modular Closthioamide Architecture Reveals Crucial Motifs of Polythioamide Antibiotics

Closthioamide, the first known secondary metabolite from an anaerobic microorganism (Clostridium cellulolyticum), represents a highly potent antibiotic that is active against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecalis (VRE) at nanomolar concentrations. To unveil structure-activity relationships of the unusual polythioamide natural product we have designed a synthetic grid to access analogues with altered terminal aromatic moieties, diverse p-phenyl substituents, different types and sizes of aliphatic spacers, varying numbers of thioamide residues, and diverse sizes and symmetries of the poly-β-thioalanyl backbone. A library of 28 closthioamide analogues was tested against a panel of human pathogenic bacteria. We found that aromatic terminal groups, the defined length of the spacer groups, the presence of all six thioamide residues and the modular arrangement of the β-thioalanyl units play essential roles for the antibiotic activity of closthioamide, yet there is a degree of freedom in the symmetry of the molecule. This study yields the first insights into pivotal structural motifs and the structural space of this new family of antibiotics, a prerequisite for the development of these promising antibiotics. Widening the scope: Structural motifs of closthioamide, the first antibiotic from strictly anaerobic microorganisms, were dissected and altered to unveil residues that are pivotal for antimicrobial activity. Using a modular approach, a library of 28 analogues was synthesized. First insights were gained into the structural space of this new family of antibiotics (see diagram).

Synthesis of chimeric tetrapeptide-linked cholic acid derivatives: Impending synergistic agents

Tetrapeptides derived from glycine and β-alanine were hooked at the C-3β position of the modified cholic acid to realize novel linear tetrapeptide-linked cholic acid derivatives. All the synthesized compounds were tested against a wide variety of microorganisms (Gram-negative bacteria, Gram-positive bacteria and fungi) and their cytotoxicity was evaluated against human embryonic kidney (HEK293) and human mammary adenocarcinoma (MCF-7) cell lines. While relatively inactive by themselves, these compounds interact synergistically with antibiotics such as fluconazole and erythromycin to inhibit growth of fungi and bacteria, respectively, at 1-24 μg/mL. The synergistic effect shown by our novel compounds is due to their inherent amphiphilicity. The fractional inhibitory concentrations reported are comparable to those reported for Polymyxin B derivatives.

Synthesis and structural study of cyclic 5-aminovaleric acid-linked β-Ala-β-Ala dipeptides

5-Aminovaleric acid and ornithine were evaluated as linkers for the cyclization of β-dipeptides. Two linked examples of β-Ala-β-Ala were prepared by standard coupling methods and their conformations probed by NMR, CD, and computational means. The data sug

Cyclic β-tetra- and pentapeptides: Synthesis through on-resin cyclization and conformational studies by X-ray, NMR and CD spectroscopy and theoretical calculations

The solution-phase synthesis of the simplest cyclic β-tetrapeptide, cyclo(β-Ala)4 (4), as well as the solid-phase syntheses through side chain anchoring and on-resin cyclization of the cyclic β3- tetrapeptide cyclo(-β3hPheβ33hLeu- β3hLys-β3hGln-) (14) and the first cyclic β3-pentapeptide cyclo(-β3hVal- β3hPhe-β3hLeu-β3hLys- β3hLys-) (19) are reported. Extensive computational as well as spectroscopic studies, including X-ray and NMR spectroscopy, were undertaken to determine the preferred conformations of these unnatural oligomers in solution and in the solid state. cyclo(β-Ala)4 (4) with no chiral side chains is shown to exist as a mixture of rapidly interchanging conformers in solution, whereas inclusion of chiral side chains in the cyclo- β3-tetrapeptide causes stabilization of one dominating conformer. The cyclic β3-pentapeptide on the other hand shows larger conformational freedom. The X-ray structure of achiral cyclo(β-Ala)4 (4) displays a Ci-symmetrical 16-membered ring with adjacent C=O and N-H atoms pointing pair wise up and down with respect to the ring plane. CD spectroscopic examinations of all cyclic β-peptides were undertaken and revealed results valuable as starting point for further structural investigations of these entities.

Acetic acid derivatives

Acetic acid derivatives of formula and hydrates, solvates and physiologically acceptable salts thereof are useful to inhibit the binding of adhesive proteins to blood platelets and also to inhibit blood platelet aggregation and cell-cell adhesion.

Low molecular weight, non-peptide fibrinogen receptor antagonists

The tetrapeptide H-Arg-Gly-Asp-Ser-OH (1) (RGDS), representing a recognition sequence of fibrinogen for its platelet receptor GP IIb-IIIa (integrin α(IIb)β3), served as lead compound for the development of highly potent and selective fibrinogen receptor antagonists. Replacement of the N- terminal arginine by p-amidinophenylalanine or the Gly moiety by m- aminobenzoic acid led to compounds which are superior to the lead peptide with regard to activity and selectivity for GP IIb-IIIa vs the closely related vitronectin receptor α(v)β3. By random screening [(p- amidinobenzenesulfonamido)ethyl]-p-phenoxyacetic acid derivatives have been identified as fibrinogen receptor antagonists. Further structure-activity relationship studies culminated in the preparation of N-[N-[N-(p- amidinobenzoyl)-β-alanyl]-L-α-aspartyl]-3-phenyl-L-alanine (29h, Ro 43- 5054) and [[1-[N-(p-amidinobenzoyl)-L-tyrosyl]-4-piperidinyl]oxy]acetic acid (37f, Ro 44-9883), which exhibit very high activity as platelet aggregation inhibitors (IC50s 0.06 and 0.03 μM, respectively, human PRP/ADP) as well as marked selectivity for GP IIb-IIIa vs α(v)β3. Since the activity of 37f in dogs declines according to a two-compartment model with an initial phase having a t( 1/2 ) of 8 min and a second phase with a t( 1/2 ) of 110 min, this compound is a suitable candidate for the development as iv platelet inhibitor.

Conformations in the Solid State and Solubility Properties of Protected Homooligopeptides of Glycine and β-Alanine

IR spectroscopic conformational analyses of Boc-Glyn-OBzl (n=3-7) and Boc-(β-Ala)n-OBzl (n=3-8) were performed in the solid state, suggesting the occurrence of the β-sheet structure in the higher oligomers (n=5-8).Solubility data ind