545433-88-3

Upstream product

• 13139-16-7 N-(tert-butyloxycarbonyl)-L-isoleucine 
• 17901-01-8 N-(tert-butoxycarbonyl)isoleucine methyl ester 
• 118517-05-8 C₁₅H₂₇NO₆ 
• 73-32-5 L-isoleucine 
• 24424-99-5 di-tert-butyl dicarbonate 
• 18598-74-8 methyl L-isoleucinate hydrochloride 
• 24629-25-2 (S)-isoleucinol 
• 66866-47-5 Boc-Ile-O-COOiBu 
• 13139-16-7 N-tert-butoxycarbonyl-D-alloisoleucine 
• 56577-28-7 methyl (2S,3S)-2-hydroxy-3-methylpentanoate 
• 1509-34-8 D-allo-isoleucine 
• 55721-65-8 Boc-D-Ile-OH 
• 248279-49-4 (2S)-2-amino-3-methyl-1-pentanol 
• 73-32-5 L-isoleucine 

Downstream Products

• 118171-79-2 N-(t-butoxycarbonyl)-isoleucine aldehyde 
• 87694-55-1 Boc-D-allo-isoleucinal 
• 1287205-76-8 tert-butyl [(2S,3S)-1-{4-bromophenyl-[(1R,2R)-2-(pyridin-2-yl)cyclopropanecarbonyl]amino}-3-methylpentan-2-yl]carbamate 

Relevant academic research and scientific papers

Urea based foldamers

N,N′-linked oligoureas are a class of enantiopure, sequence-defined peptidomimetic oligomers without amino acids that form well-defined and predictable helical structures akin to the peptide α-helix. Oligourea-based foldamers combine a number of features—such as synthetic accessibility, sequence modularity, and folding fidelity—that bode well for their use in a range of applications from medicinal chemistry to catalysis. Moreover, it was recently recognized that this synthetic helical backbone can be combined with regular peptides to generate helically folded peptide-oligourea hybrids that display additional features in terms of helix mimicry and protein-surface recognition properties. Here we provide detailed protocols for the preparation of requested monomers and for the synthesis and purification of homo-oligoureas and peptide-oligourea hybrids.

Asymmetric kinetic resolution of sulfides for the construction of unsymmetric sulfides and chiral 3,3-disubstituted oxindoles

A range of 3,3-disubstituted oxindoles accessed using para-quinone methides derived from isatins with thiols were used for the formation of unsymmetrical disulfides, and 3,3-disubstituted oxindoles with a chiral quaternary carbon center and unsymmetric di

Design, synthesis, and structure-activity relationship studies of L-amino alcohol derivatives as broad-spectrum antifungal agents

To discover broad spectrum antifungal agents, two strategies were applied, and a novel class of L-amino alcohol derivatives were designed and synthesized. 3-F substituted compounds 14i, 14n, 14s and 14v exhibited excellent antifungal activities with broad antifungal spectra against C. albicans and C. tropicalis, with MIC values in the range of 0.03–0.06 μg/mL, and against A. fumigatus and C. neoformans, with MIC values in the range of 1–2 μg/mL. Notably, Compounds 14i, 14n, 14s and 14v also displayed moderate activities against fluconazole-resistance strains 17# and CaR that were isolated from AIDS patients. Moreover, only compounds in the S-configuration showed antifungal activity. Preliminary mechanistic studies showed that the potent antifungal activity of compound 14v stemmed from inhibition of C. albicans CYP51. Compounds 14n and 14v were almost nontoxic to mammalian A549 cells, and their stability in human plasma was excellent.

Synthesis, biological evaluation, and molecular modeling studies of chiral chloroquine analogues as antimalarial agents

In a focused exploration, we designed, synthesized, and biologically evaluated chiral conjugated new chloroquine (CQ) analogues with substituted piperazines as antimalarial agents. In vitro as well as in vivo studies revealed that compound 7c showed potent activity (in vitro 50% inhibitory concentration, 56.98 nM for strain 3D7 and 97.76 nM for strain K1; selectivity index in vivo [up to at a dose of 12.5 mg/kg of body weight], 3,510) as a new lead antimalarial agent. Other compounds (compounds 6b, 6d, 7d, 7h, 8c, 8d, 9a, and 9c) also showed moderate activity against a CQ-sensitive strain (3D7) and superior activity against a CQ-resistant strain (K1) of Plasmodium falciparum. Furthermore, we carried out docking and three-dimensional quantitative structure-activity relationship (3D-QSAR) studies of all in-house data sets (168 molecules) of chiral CQ analogues to explain the structure-activity relationships (SAR). Our new findings specify the significance of the H-bond interaction with the side chain of heme for biological activity. In addition, the 3D-QSAR study against the 3D7 strain indicated the favorable and unfavorable sites of CQ analogues for incorporating steric, hydrophobic, and electropositive groups to improve the antimalarial activity.

Synthesis, SAR and biological studies of sugar amino acid-based almiramide analogues: N-methylation leads the way

Leishmaniasis, caused by the protozoan parasites of the genus Leishmania, is one of the most neglected diseases endemic in many continents posing enormous global health threats and therefore the discovery of new antileishmanial compounds is of utmost urgency. The antileishmanial activities of a library of sugar amino acid-based linear lipopeptide analogues were examined with the aim to identify potential drug candidates to treat visceral leishmaniasis. It was found that among the synthesized analogues, most of the permethylated compounds exhibited more activity in in vitro studies against intra-macrophagic amastigotes than the non-methylated analogues. SAR and NMR studies revealed that introduction of the N-methyl groups inhibited the formation of any turn structure in these molecules, which led to their improved activities.

Synthesis and biological activity evaluation of dolastatin 10 analogues with N-terminal modifications

We have described the synthesis of the two complex units (2R,3R,4S)-dolaproine (Dap) and (3R,4S,5S)-dolaisoleuine (Dil) of dolastatin 10 from natural amino acids. The stereoselective syntheses of N-Boc-Dap (4a) and N-Boc-(2S)-iso-Dap (4b) were performed by employing crotylation of N-Boc-L-prolinal as a key step. Barbier-type allylation of N-Boc-L-isoleucinal provided a mild and convenient approach for the synthesis of N-Boc-Dil (5a) and N-Boc-(3S)-iso-Dil (5b). Ten dolastatin 10 analogues have been designed and synthesized with N-terminal modifications based on the known compound monomethylauristatin F (MMAF, 3). In comparison with MMAF (3), four of the compounds showed enhanced potency against HCT 116 human colon cancer cells in?vitro.

Chemo- and Diastereoselective N-Heterocyclic Carbene-Catalyzed Cross-Benzoin Reactions Using N-Boc-α-amino Aldehydes

N-Boc-α-amino aldehydes are shown to be excellent partners in cross-benzoin reactions with aliphatic or heteroaromatic aldehydes. The chemoselectivity of the reaction and the facial selectivity on the amino aldehyde allow cross-benzoin products to be obtained in good yields and good diastereomeric ratios. The developed method is utilized as the key step in a concise total synthesis of d-arabino-phytosphingosine.

Design, synthesis and evaluation of novel indole derivatives as AKT inhibitors

Herein, we describe the discovery and synthesis of a new series of 1,2,4,7-tetra-substituted indole derivatives as novel AKT inhibitors by optimization of a weak hit methyl 4-(2-aminoethoxy)-1H-indole-2-carboxylate (1). Both representative compounds 6a and 6o exhibited the most potent inhibitory activities against AKT1, with inhibition rates of 72.5% and 78.6%, respectively, at concentrations of 10 nM. In addition, compounds 6a and 6o also potently inhibited the phosphorylation of the downstream GSK3 protein and displayed slightly better anti-proliferative activities in a prostate cancer cell line.

A rapid entry to amino acid derived diverse 3,4-dihydropyrazines and dihydro[1,2,3]triazolo[1,5-a]pyrazines through 1,3-dipolar cycloaddition

An efficient, general and practical synthesis of diverse 3,4-dihydropyrazines, 6,7-dihydro-[1,2,3]triazolopyrazines and 7,8-dihydro-[1,2,3]triazolodiazepines through intramolecular 1,3-dipolar cycloaddition from amino acid derived common intermediates with high yields is described. Moreover, one-pot access to optically active 3-aryl substituted 6,7-dihydro-[1,2,3]triazolo[1,5-a]pyrazines in the palladium-copper co-catalytic system has also been achieved in this work. The easy substrate availability and operational simplicity make the process suitable for further exploration. This journal is the Partner Organisations 2014.

Building a macrocyclic toolbox from C-linked carbohydrates identifies antiangiogenesis agents from zebrafish assay

We report the synthesis of four different types of macrocyclic-derived glycohybrids from carbohydrates that have an amino acid moiety in the large-ring skeleton. These macrocyclic glycohybrids were obtained from α-C-1H- and β-C-1H-linked carbohydrates. In one series, we utilized ring-closing metathesis as the "stitching technology" to obtain two different macrocycles, i.e., trans equatorial-axial C-1H and C-5H and cis axial-axial C-1H and C-5H. The click approach was the key reaction in our second series to obtain two other macrocyclic compounds, i.e., trans equatorial-axial C-1H and C-5H and cis axial-axial C-1H and C-5H. The evaluation of this toolbox resulted in the identification of two unique compounds as antiangiogenesis agents in an embryonic zebrafish assay. Interestingly, in both cases, the macrocyclic compounds that have a cis relationship (i.e., axial-axial orientation) between C-1H and C-5H showed activity and their other diastereomers (i.e., equatorial-axial C-1H and C-5 H) with a trans relationship did not show any effect. The synthesis of four different types of macrocyclic glycohybrids that contain an amino acid moiety in the large-ring skeleton is reported. Ring-closing metathesis and click chemistry approaches were utilized to obtain two different series of macrocycles. The evaluation of this toolbox resulted in the identification of two unique compounds as antiangiogenesis agents in an embryonic zebrafish assay. Copyright