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COMPOUNDS AND METHODS OF USE
Disclosed are heterocyclic compounds or their pharmaceutically acceptable salts with ferroptosis-inducing activity, Those compounds or their pharmaceutically acceptable salts can be used to treat cancer.
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(2022/03/09)

Thiamine hydrochloride as a recyclable organocatalyst for the efficient and chemoselective N-tert-butyloxycarbonylation of amines
Thiamin hydrochloride promoted highly efficient and ecofriendly approach has been described for the chemoselective N-tert-butyloxycarbonylation of amines under solvent-free conditions at ambient temperature. The demonstrated approach has been applicable for the N-Boc protection of variety of aliphatic, aryl, heteroaryl amines. The chemoselective protection of amino group occurs in chiral amines and amino alcohol without racemization in high yield. Thiamin hydrochloride is stable, economical, easy to handle and environmentally friendly.
Ingale, Ajit P.,Garad, Dnyaneshwar N.,Ukale, Dattatraya,Thorat, Nitin M.,Shinde, Sandeep V.
supporting information
p. 3791 - 3804
(2021/11/04)

Sulfated tungstate: A highly efficient, recyclable and ecofriendly catalyst for chemoselective N-tert butyloxycarbonylation of amines under the solvent-free conditions
Sulfated tungstate catalyzed an efficient and ecofriendly protocol has been described for the chemoselective N-tert-butyloxycarbonylation of amines under the solvent-free conditions at room temperature. The variety of functionalized aliphatic, aromatic and heteroaromatic amines efficiently undergoes the N-tert-butyloxycarbonylation under the developed protocol. The aminoalcohol, aminophenol, aminoester as well as various chiral amines underwent the chemoselective N-Boc protection under the optimized reaction condition. The rapid reaction rate, mild conditions, very good functional group tolerance, excellent yield, solvent-free, easy recovery products and excellent catalyst recyclability are the advantages of this protocol. This makes the protocol feasible, economical and environmentally benign.
Ingale, Ajit P.,Shinde, Sandeep V.,Thorat, Nitin M.
supporting information
p. 2528 - 2543
(2021/07/02)

Nanoceria as an efficient and green catalyst for the chemoselective N-tert-butyloxycarbonylation of amines under the solvent-free conditions
Nanocerium oxide mediated an efficient and green protocol has been described for the chemoselective N-tert-butyloxycarbonylation of amines under the solvent-free conditions at ambient temperature. Various aliphatic, aromatic and heteroaromatic amines were protected using developed protocol and several functional groups such as alcohol, phenol and ester were well tolerated under these conditions. The rapid reaction rate, mild conditions, very good functional group tolerance, excellent yield, solvent-free, easy recovery products and excellent catalyst recyclability are the advantages of this protocol. This makes the protocol feasible, economical and environmentally benign.
Garad, Dnyaneshwar N.,Ingale, Ajit P.,Shinde, Sandeep V.,Ukale, Dattatraya
supporting information
p. 1656 - 1668
(2021/04/05)

Structure Determination, Biosynthetic Origin, and Total Synthesis of Akazaoxime, an Enteromycin-Class Metabolite from a Marine-Derived Actinomycete of the Genus Micromonospora
A new enteromycin-class antibiotic, akazaoxime (1), possessing an aldoxime functionality in place of O-methyl nitronic acid, was isolated from the cultured extract of a marine-derived actinomycete of the genus Micromonospora, along with known A-76356 (2). The structure of 1, including the absolute stereochemistry of three chiral centers, was established by comprehensive analysis of nuclear magnetic resonance (NMR) and mass spectrometry data coupled with magnetic anisotropy analysis of its phenylglycine methyl ester derivatives. The stereochemistry of 2, not determined previously, was proven to be the same as that of 1 on the basis of the similarity of their NMR and specific rotation data. Precursor feeding experiments using 13C-labeled compounds elucidated that the carbon skeletons of 1 and 2 are constructed from propionate (methylmalonate), leucine, and glycine. Establishment of the concise and flexible synthetic route to 1 enabled us to implement biological evaluation of 1 and its unnatural analogues, demonstrating weak to moderate antimicrobial activities of 1 against Gram-positive Kocuria rhizophila [minimum inhibitory concentration (MIC) of 50 μg/mL] and those of synthetic analogues against a plant pathogen Glomerella cingulata (MIC of 50 μg/mL) and a human pathogen Trichophyton rubrum (MIC of 25-50 μg/mL).
Igarashi, Yasuhiro,Matsuyuki, Yoe,Yamada, Masayuki,Fujihara, Nodoka,Harunari, Enjuro,Oku, Naoya,Karim, Md. Rokon Ul,Yang, Taehui,Yamada, Katsuhisa,Imada, Chiaki,Fukaya, Keisuke,Urabe, Daisuke
p. 6528 - 6537
(2021/05/29)

Ultrasound promoted environmentally benign, highly efficient, and chemoselective N-tert-butyloxycarbonylation of amines by reusable sulfated polyborate
The sulfated polyborate catalyzed an efficient and chemoselective N-tert-butyloxycarbonylation of amines under ultrasonic irradiation is developed. A broad substrate scope has been demonstrated for N-Boc protection of various primary/secondary amines. It allows converting several aliphatic/aryl/heteroaryl amines, amino alcohol, aminoester, and chiral amines to their N-Boc-protected derivatives under solvent-free conditions with excellent yields. The protocol has several advantages such as easy catalyst, and product isolation, short reaction time, excellent yields, outstanding chemoselectivity, and catalyst recyclability, among others. This makes the process practicable, economical, and environmentally benign.
Pise, Ashok S.,Ingale, Ajit P.,Dalvi, Navnath R.
supporting information
p. 3768 - 3780
(2021/10/26)

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.
Yoo, Sung Hyun,Li, Bo,Dolain, Christel,Pasco, Morgane,Guichard, Gilles
p. 59 - 92
(2021/06/25)

Asymmetric 1,4-Addition Reactions Catalyzed by N-Terminal Thiourea-Modified Helical l-Leu Peptide with Cyclic Amino Acids
N-terminal thiourea-modified l-Leu-based peptide {(3,5-diCF3Ph)NHC(=S)-(l-Leu-l-Leu-Ac5c)2-OMe} with five-membered ring α,α-disubstituted α-amino acids (Ac5c) catalyzed a highly enantioselective 1,4-addition reaction between β-nitrostyrene and dimethyl malonate. The enantioselective reaction required only 0.5 mol % chiral peptide-catalyst in the presence of iPr2EtN (2.5 equiv.), and gave a 1,4-adduct with 93 % ee of an 85 % yield. As Michael acceptors, various β-nitrostyrene derivatives such as methyl, p-fluoro, p-bromo, and p-methoxy substituents on the phenyl group, 2-furyl, 2-thiophenyl, and naphthyl β-nitroethylenes could be applied. Furthermore, various alkyl malonates and cyclic β-keto-esters could be used as Michael donors. It became clear that the length of the peptide chain, a right-handed helical structure, amide N?Hs, and the N-terminal thiourea moiety play crucial roles in asymmetric induction.
Sato, Kazuki,Umeno, Tomohiro,Ueda, Atsushi,Kato, Takuma,Doi, Mitsunobu,Tanaka, Masakazu
supporting information
p. 11216 - 11220
(2021/06/21)

Vinyl sulfone-based inhibitors of trypanosomal cysteine protease rhodesain with improved antitrypanosomal activities
The number of reported cases of Human African Trypanosmiasis (HAT), caused by kinetoplastid protozoan parasite Trypanosoma brucei, is declining in sub-Saharan Africa. Historically, such declines are generally followed by periods of higher incidence, and one of the lingering public health challenges of HAT is that its drug development pipeline is historically sparse. As a continuation of our work on new antitrypanosomal agents, we found that partially saturated quinoline-based vinyl sulfone compounds selectively inhibit the growth of T. brucei but displayed relatively weak inhibitory activity towards T. brucei's cysteine protease rhodesain. While two nitroaromatic analogues of the quinoline-based vinyl sulfone compounds displayed potent inhibition of T. brucei and rhodesain. The quinoline derivatives and the nitroaromatic-based compounds discovered in this work can serve as leads for ADME-based optimization and pre-clinical investigations.
Ajayi, Oluwatomi,Collins, Jasmine,Crown, Olamide,Nyamwihura, Rogers,Ogungbe, Ifedayo Victor,Zhang, Huaisheng
supporting information

(2020/05/18)

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.
Zhao, Liyu,Tian, Linfeng,Sun, Nannan,Sun, Yin,Chen, Yixuan,Wang, Xinran,Zhao, Shizhen,Su, Xin,Zhao, Dongmei,Cheng, Maosheng
p. 374 - 385
(2019/06/05)

COMPOSITION FOR TREATMENT AND/OR PREVENTION OF PERIPHERAL NERVE DISORDER
The present invention provides a means for treating and/or preventing peripheral nerve disorder by facilitating regeneration of peripheral nerves. Specifically, the present invention provides a composition for treating and/or preventing peripheral nerve d
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(2019/10/29)

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.
Kondaparla, Srinivasarao,Debnath, Utsab,Dola, Vasantha Rao,Sinha, Manish,Katti, Seturam B.,Soni, Awakash,Srivastava, Kumkum,Puri, Sunil K.
(2019/01/05)

Synthesis of Enantiomerically Pure 3-Substituted Piperazine-2-acetic Acid Esters as Intermediates for Library Production
The piperazine heterocycle is broadly exploited in FDA-approved drugs and biologically active compounds, but its chemical diversity is usually limited to ring nitrogen substitutions, leaving the four carbon atoms underutilized. Using an efficient six-step synthesis, chiral amino acids were transformed into 3-substituted piperazine-2-acetic acid esters as diastereomeric mixtures whose cis and trans products (dr 0.56 a? 2.2:1, respectively) could be chromatographically separated. From five amino acids (both antipodes) was obtained a complete matrix of 20 monoprotected chiral 2,3-disubstituted piperazines, each as a single absolute stereoisomer, all but one in multigram quantities. In keeping with our overall purpose of constructing more Csp3-enriched compound libraries for drug discovery, these diverse and versatile piperazines can be functionalized on either nitrogen atom, allowing them to be used as scaffolds for parallel library synthesis and as intermediates for the production of novel piperazine compounds.
Reddy Guduru, Shiva Krishna,Chamakuri, Srinivas,Raji, Idris O.,MacKenzie, Kevin R.,Santini, Conrad,Young, Damian W.
p. 11777 - 11793
(2018/09/27)

Copper nanoparticles catalyzed N-H functionalization: An efficient solvent-free N-tert-butyloxycarbonylation strategy
A chemoselective transformation of amines to their tert-butyloxycarbonyl (Boc) protected derivatives (NBoc) is described using Cu-NPs under solvent-free conditions. Simple method, rapid reaction rate, mild conditions, tolerance of a wide range of functional groups, excellent yield, ease recovery and high catalytic turnover are the salient features of this approach. tert-Butyloxycarbonylation of chiral amino acid esters and amino alcohols were performed without racemization.
Deb, Barnali,Debnath, Sudipto,Deb, Anindita,Maiti, Dilip K.,Majumdar, Swapan
supporting information
p. 629 - 633
(2017/01/25)

A new family of 1,2,3-oxathiazolidine-2,2-dioxide phosphonate derivatives: Synthesis, characterization and anticancer evaluation
An efficient synthesis of a new series of organophosphorus compounds having a cyclic sulfamidates moiety is described. The cyclic sulfamidate precursors were prepared from α-amino acids after four steps (Reduction, N-Boc protection, cyclization and cleavage). The novel organophosphonates were synthesized within two steps starting from the cyclic sulfamidate (chloroacetylation following by phosphorylation via Arbuzov reaction). A particular compound 7-a (diethyl phosphonate {2-[(4S)-4-benzyl-1,2,3-oxathiazolidin-3-yl-2,2-dioxyde]-2-oxoethyl}) was essayed for their in vitro cytotoxic activities against a panel of four cell lines (Jurkat, K562, U266, and A431). For all of these cells, the synthesized compound showed low cytotoxicity, even at high concentration levels (4?mM).
K'tir, Hacène,Aouf, Zineb,Souk, Tan Otea,Zerrouki, Rachida,Berredjem, Malika,Aouf, Nour-Eddine
p. 555 - 559
(2017/05/01)

Synthesis and antimalarial activity of new 4-aminoquinolines active against drug resistant strains
In the present study we have synthesized a new class of 4-aminoquinoline derivatives via replacement of the diethylamine functionality of chloroquine (CQ) with acyclic and/or cyclic amine groups containing basic tertiary terminal nitrogen and bioevaluated them for antimalarial activity against Plasmodium falciparum in vitro (CQ-sensitive strain-3D7 & CQ-resistant strain-K1) and Plasmodium yoelii in vivo (N-67 strain). Among the series, thirteen compounds showed superior antimalarial activity against K1 strain as compared to CQ. In addition, all these analogs showed 100% suppression of parasitaemia on day 4 in the in vivo mouse model against N-67 strain when administered orally. Further, biophysical studies suggest that these compounds act on the heme polymerization target.
Kondaparla, Srinivasarao,Soni, Awakash,Manhas, Ashan,Srivastava, Kumkum,Puri, Sunil K.,Katti
p. 105676 - 105689
(2016/11/18)

Discovery of (S)-4-isobutyloxazolidin-2-one as a novel leucyl-tRNA synthetase (LRS)-targeted mTORC1 inhibitor
A series of leucinol analogs were investigated as leucyl-tRNA synthetase-targeted mTORC1 inhibitors. Among them, compound 5, (S)-4-isobutyloxazolidin-2-one, showed the most potent inhibition on the mTORC1 pathway in a concentration-dependent manner. Compound 5 inhibited downstream phosphorylation of mTORC1 by blocking leucine-sensing ability of LRS, without affecting the catalytic activity of LRS. In addition, compound 5 exhibited cytotoxicity against rapamycin-resistant colon cancer cells, suggesting that LRS has the potential to serve as a novel therapeutic target.
Yoon, Suyoung,Kim, Jong Hyun,Yoon, Ina,Kim, Changhoon,Kim, Sung-Eun,Koh, Yura,Jeong, Seung Jae,Lee, Jiyoun,Kim, Sunghoon,Lee, Jeewoo
p. 3038 - 3041
(2016/06/13)

Lissencephaly therapeutic agent
An object of the present invention is to provide a medicament and method for treating lissencephaly patients. The present invention provides a lissencephaly therapeutic or preventive agent comprising a compound represented by the general formula (I): wher
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(2016/07/27)

Investigations on the [2,3]-Wittig Rearrangement of Chiral 4-Aminopropargyloxy Acetates to Novel α-Hydroxy-γ-amino Acids Containing an Allene Unit
The [2,3]-Wittig rearrangement of propargyloxy acetates bearing a propargylic stereocenter opposite to the oxyacetic acid moiety gives α-hydroxy-γ-amino acids containing an allene unit under high stereocontrol. The resulting product displays a novel type of γ-amino acid with a potentially intriguing biological profile.
Griebenow, Nils,Cumine, Florimond,Dilmac, Alicia M.
p. 1702 - 1704
(2015/07/20)

ARYL ETHER-BASE KINASE INHIBITORS
The present disclosure is generally directed to compounds which can inhibit AAK1 (adaptor associated kinase 1), compositions comprising such compounds, and methods for inhibiting AAK1.
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(2015/03/28)

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.
Yang, Dezhi,Wang, Peng,Liu, Jianzhen,Xing, Hualu,Liu, Yang,Xie, Wencheng,Zhao, Guisen
p. 366 - 373
(2014/01/17)

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.
Bera, Saurav,Panda, Gautam
p. 3976 - 3985
(2014/06/09)

Hydrodehalogenation of alkyl iodides with base-mediated hydrogenation and catalytic transfer hydrogenation: Application to the asymmetric synthesis of N-protected α-methylamines
We report a very mild synthesis of N-protected α-methylamines from the corresponding amino acids. Carboxyl groups of amino acids are reduced to iodomethyl groups via hydroxymethyl intermediates. Reductive deiodination to methyl groups is achieved by hydrogenation or catalytic transfer hydrogenation under alkaline conditions. Basic hydrodehalogenation is selective for the iodomethyl group over hydrogenolysis-labile protecting groups, such as benzyloxycarbonyl, benzyl ester, benzyl ether, and 9-fluorenyloxymethyl, thus allowing the conversion of virtually any protected amino acid into the corresponding N-protected α-methylamine.
Mandal, Pijus K.,Birtwistle, J. Sanderson,McMurray, John S.
p. 8422 - 8427
(2015/03/18)

General solvent-free highly selective N-tert-butyloxycarbonylation strategy using protic ionic liquid as an efficient catalyst
A simple, rapid and solvent-free protocol is described for the chemo-selective transformation of amines to tert-butyloxycarbonyl protected derivatives (NHBoc) using Boc2O and imidazolium trifluoroacetate protic ionic liquid (5-20 mol%). Unwanted side products such as isocyanate, urea or N,N-di-Boc were not detected. The scope of the protection strategy was successfully explored for substrate alcohols, phenols and thiol at elevated temperatures. Optically pure amino acids, amino acid esters and amino alcohols were efficiently converted to the corresponding N-Boc protected derivatives in excellent yields without racemization at the chiral center. The distinct advantages of this method are: operational simplicity, cleaner reaction, high selectivity, excellent yield, rapid reaction convergence, easy preparation and recyclability of the catalyst.
Majumdar, Swapan,De, Jhinuk,Chakraborty, Ankita,Maiti, Dilip K.
p. 24544 - 24550
(2014/07/07)

A two-step synthesis of the bioprotective agent JP4-039 from N-Boc-l-leucinal
An expedited synthesis of the bioprotective agent JP4-039 is described from N-Boc-l-leucinal in 50% overall yield. The synthesis involves the use of an α,unsaturated diazoketone as the key intermediate, followed by a photochemical Wolff rearrangement in t
Bernardim, Barbara,Burtoloso, Antonio C.B.
p. 3291 - 3296
(2014/05/06)

A multifaceted secondary structure mimic based on piperidine-piperidinones
Minimalist secondary structure mimics are typically made to resemble one interface in a protein-protein interaction (PPI), and thus perturb it. We recently proposed suitable chemotypes can be matched with interface regions directly, without regard for secondary structures. Here we describe a modular synthesis of a new chemotype 1, simulation of its solution-state conformational ensemble, and correlation of that with ideal secondary structures and real interface regions in PPIs. Scaffold 1 presents amino acid side-chains that are quite separated from each other, in orientations that closely resemble ideal sheet or helical structures, similar non-ideal structures at PPI interfaces, and regions of other PPI interfaces where the mimic conformation does not resemble any secondary structure. 68 different PPIs where conformations of 1 matched well were identified. A new method is also presented to determine the relevance of a minimalist mimic crystal structure to its solution conformations. Thus dld-1-faf crystallized in a conformation that is estimated to be 0.91 kcal-mol-1 above the minimum energy solution state. Do we know, when designing a new peptidomimetic scaffold like the one shown, how it can resemble secondary structures? Design and modular synthesis of this elongated mimic is reported, and the structure is related to ideal and real structures at PPI interfaces.
Xin, Dongyue,Perez, Lisa M.,Ioerger, Thomas R.,Burgess, Kevin
p. 3594 - 3598
(2014/04/17)

A simple, rapid, and efficient N-Boc protection of amines under ultrasound irradiation and catalyst-free conditions
A green and simple approach for the N-Boc protection on structurally diverse amines under ultrasound irradiation is described. Selective N-Boc protection was achieved in excellent isolated yield in a short reaction time at room temperature. Mild conditions, inexpensive and an easily available reagent, and absence of any auxiliary substances are the main advantages of this procedure. Graphical abstract: [Figure not available: see fulltext.]
Amira, Aicha,K'Tir, Hacene,Berredjem, Malika,Aouf, Nour-Eddine
p. 509 - 515
(2014/03/21)

Aryl Ether-Base Kinase Inhibitors
The present disclosure is generally directed to compounds which can inhibit AAK1 (adaptor associated kinase 1), compositions comprising such compounds, and methods for inhibiting AAK1.
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(2013/09/26)

Tetrahydroquinoline-derived macrocyclic toolbox: The discovery of antiangiogenesis agents in zebrafish assay
A novel approach to incorporate the macrocyclic rings onto the privileged substructure, i.e., tetrahydroquinoline scaffold, is developed. The presence of an amino acid-derived moiety in the macrocyclic skeleton provides an opportunity to modulate the nature of the chiral side chain. Further, evaluation in a zebrafish screen identified three active small molecules (2.5b, 3.2d, and 4.2) as antiangiogenesis agents at 2.5 μM.
Reddy Guduru, Shiva Krishna,Chamakuri, Srinivas,Chandrasekar, Gayathri,Kitambi, Satish Srinivas,Arya, Prabhat
supporting information
p. 666 - 670
(2013/07/26)

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
Jogula, Srinivas,Dasari, Bhanudas,Khatravath, Mahender,Chandrasekar, Gayathri,Kitambi, Satish Srinivas,Arya, Prabhat
supporting information
p. 5036 - 5040
(2013/11/06)

β3R3-Peptides: Design and synthesis of novel peptidomimetics and their self-assembling properties at the air-water interface
In this study we present the design and synthesis of a novel class of peptidomimetics, the β3R3-peptides. Via alternating directions of the amide bonds along β-peptide sequences, β3R3-peptides can potentially extend the structural space available to β-peptidic foldamers. Detailed analysis at the air-water interface shows strand conformations and the formation of sheet assemblies with different degrees of crystallinity. Furthermore β3R3-peptides exhibit a high proteolytic stability thus making them an interesting new class of peptidomimetics for biomedical applications. The Royal Society of Chemistry.
Mosca, Simone,Dannehl, Claudia,M?ginger, Uwe,Brezesinski, Gerald,Hartmann, Laura
p. 5399 - 5403
(2013/09/02)

LISSENCEPHALY THERAPEUTIC AGENT
An object of the present invention is to provide a medicament and method for treating lissencephaly patients. The present invention provides a lissencephaly therapeutic or preventive agent comprising a compound represented by the general formula (I): wher
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(2013/10/22)

Catalytic asymmetric [4+2] annulation initiated by an aza-rauhut-currier reaction: Facile entry to highly functionalized tetrahydropyridines
Under control: The first example of chiral amino phosphine catalysts for the title reaction between vinyl ketones and N-sulfonyl-1-aza-1,3-dienes has been developed. Under ambient conditions, this protocol provides straightforward access to densely functionalized, enantioenriched tetrahydropyridines with high levels of sterecontrol in good to excellent yields. Copyright
Shi, Zugui,Yu, Peiyuan,Loh, Teck-Peng,Zhong, Guofu
supporting information; scheme or table
p. 7825 - 7829
(2012/09/08)

Synthesis of imidacloprid derivatives with a chiral alkylated imidazolidine ring and evaluation of their insecticidal activity and affinity to the nicotinic acetylcholine receptor
A series of imidacloprid (IMI) derivatives with an alkylated imidazolidine ring were asymmetrically synthesized to evaluate their insecticidal activity against adult female housefly, Musca domestica, and affinity to the nicotinic acetylcholine receptor of the flies. The bulkier the alkyl group, the lower was the receptor affinity, but the derivatives methylated and ethylated at the R-5-position of the imidazolidine ring were equipotent to the unsubstituted compound. Quantitative structure-activity relationship (QSAR) analysis of the receptor affinity demonstrated that the introduction of a substituent into the imidazolidine ring was fundamentally disadvantageous, but the introduction of a substituent at the R-5-position was permissible in the case of its small size. The binding model of the synthesized derivatives with the receptor supported the QSAR analysis, indicating the existence of space for a short alkyl group around the R-5-position in the ligand-binding site. In addition, positive correlation was observed between the insecticidal activity and receptor affinity, suggesting that the receptor affinity was the primary factor in influencing the insecticidal activity even if the imidazolidine ring was modified.
Nishiwaki, Hisashi,Kuriyama, Mituhiro,Nagaoka, Hikaru,Kato, Akira,Yamauchi, Satoshi,Shuto, Yoshihiro,Akamatsu, Miki
p. 6305 - 6312,8
(2012/12/11)

RTD-1 mimic containing γPNA scaffold exhibits broad-spectrum antibacterial activities
Macrocyclic peptides with multiple disulfide cross-linkages, such as those produced by plants and those found in nonhuman primates, as components of the innate immunity, hold great promise for molecular therapy because of their broad biological activities
Rapireddy, Srinivas,Nhon, Linda,Meehan, Robert E.,Franks, Jonathan,Stolz, Donna Beer,Tran, Dat,Selsted, Michael E.,Ly, Danith H.
p. 4041 - 4044
(2012/04/10)

Microwave-enhanced solid-phase synthesis of N,N′-linked aliphatic oligoureas and related hybrids
A practical and efficient microwave-assisted solid-phase method for the synthesis of N,N′-linked oligoureas and related amide/urea hybrid oligomers, featuring the use of succinimidyl (2-azido-2-substituted ethyl) carbamate monomers, is reported. The rate enhancement of urea formation under microwave irradiation combined with the mild conditions of the phosphine-based azide reduction makes this approach very effective for routine synthesis of oligoureas and possibly for library production.
Douat-Casassus, Céline,Pulka, Karolina,Claudon, Paul,Guichard, Gilles
supporting information; experimental part
p. 3130 - 3133
(2012/09/08)

A facile synthesis and crystallographic analysis of N-protected β-amino alcohols and short peptaibols
A facile, efficient and racemization-free method for the synthesis of N-protected β-amino alcohols and peptaibols using N-hydroxysuccinimide active esters is described. Using this method, dipeptide, tripeptide and pentapeptide alcohols were isolated in high yields. The conformations in crystals of β-amino alcohol, dipeptide and tripeptide alcohols were analysed, with a well-defined type III β-turn being observed in the tripeptide alcohol crystals. This method is found to be compatible with Fmoc-, Boc- and other side-chain protecting groups.
Jadhav, Sandip V.,Bandyopadhyay, Anupam,Benke, Sushil N.,Mali, Sachitanand M.,Gopi, Hosahudya N.
supporting information; experimental part
p. 4182 - 4187
(2011/06/28)

Synthesis and binding properties of guanidinium biscarboxylates
The ammonium ion binding site of the enzyme glutaminase HisF inspired us to design guanidinium biscarboxylates as potential self-organized ionophores in molecular recognition. The syntheses of the title compounds based on aliphatic and aromatic building b
Spaeth, Andreas,Gonschor, Janina,Koenig, Burkhard
experimental part
p. 1289 - 1308
(2012/06/15)

Synthesis of chiral iodo-N,O-acetonide aminal scaffolds via an efficient cascade reaction of amino acid-derived epoxides
Novel amino acid-derived iodo-N,O-acetonide aminals were developed as chiral, non-epimerizable scaffolds to facilitate complex molecule synthesis. These scaffolds are readily prepared from commercially available amino acid derivatives in ≤6 steps, contain an orthogonally-protected β-hydroxy amine moiety, and feature a directly reactive alkyl-iodide group for facile substitution chemistry. Further, a novel ring opening/cyclization cascade reaction was developed to prepare these compounds efficiently (59-72%) from readily available epoxide derivatives.
Paige Souder,Evans, Zachary M.,Driver, Joshua A.,Pozzo, Eric J.,Lampkins, Andrew J.
scheme or table
p. 6908 - 6910
(2012/02/15)

Synthesis and preliminary evaluation of peptidomimetic inhibitors of human β-secretase
Based on the structure of OM99-2 and the X-ray crystal structure of its complex with β-secretase, a series of compounds containing the Leu*Ala hydroxyethylene isostere as a scissile bond substitution were designed. 31 compounds were synthesized and their
Niu, Yan,Wang, Yuehua,Zou, Xiaomin,Yang, Xiaoming,Ma, Chao,Lü, Yang,Zhou, Bo,Yuan, Yue,Du, Guanhua,Xu, Ping
scheme or table
p. 2089 - 2094
(2010/06/17)

Addition of allylzinc to a-amino acid-derived imines: Synthesis of diamino alcohols by Hydroboration
Imines obtained by condensation of Z-pro- tected or Boc-protected α-amino aldehydes with α-amino tert-butyl esters or with O-silyl-protected amino alcohols were reacted with preformed allyl zinc yielding homoal- lylamines with yields around 50% and selectivities ranging from 50:50 to 90:10. Hydroboration of the terminal double bond furnished diamino alcohols with yields up to 97%. The configuration of the substrates was determined by X-ray-crystallographic analysis of a hydroboration product and comparison of physical data. Springer-Verlag 2010.
Virlouvet, Mickael,Goesmann, Helmut,Feldmann, Claus,Podlech, Joachim
experimental part
p. 177 - 198
(2010/08/05)

Synthesis, preferred conformation, and membrane activity of medium-length peptaibiotics: Tylopeptin B
The solid-phase synthesis and full chemical characterization of the medium-length (14-amino acid residues) peptaibol with antibiotic properties of tylopeptin B, originally extracted from the fruiting body of the mushroom Tylopilus neofelleus, are described. These data are accompanied by the results on the solution-phase synthesis via the segment condensation approach of a selected, side-chain protected, analog. A solution conformational analysis, performed by the combined use of FTIR absorption, circular dichroism, and 2D-NMR (the latter technique coupled to molecular dynamics calculations), favors the conclusion that the 3D-structure of tylopeptin B is largely helical with a preference for the α- or the 310-helix type depending upon the nature of the solvent. Helix topology and (partial) amphiphilic character are responsible for the observed membrane-modifying properties of this peptaibiotic.
Gobbo, Marina,Poloni, Claudia,De Zotti, Marta,Peggion, Cristina,Biondi, Barbara,Ballano, Gema,Formaggio, Fernando,Toniolo, Claudio
experimental part
p. 169 - 181
(2011/02/23)

A versatile synthetic platform based on strained propargyl amines
"Chemical Equation Presented" Divergent reactivity: Various ethynylaziridines behave as strained propargyl amines and can be directly converted into unprotected α-amino allenes by a highly diastereoselective SN2′ hydride delivery (see scheme). Additional reaction routes involve chemo- and regioselective transformation into either bicyclic aziridine/ enol ethers or highly strained azirine alkynes.
He, Zhi,Yudin, Andrei K.
p. 1607 - 1610
(2010/06/16)

Resolution of N-Protected amino alcohols by porcine pancreatic lipase
The resolution of 2-amino alcohols protected by urethane-type groups either via porcine pancreatic lipase (PPL) hydrolysis of the corresponding racemic acetates or via PPL catalyzed transesterification of racemic alcohols was studied. In both cases, Boc protecting group led to better chemical yields and enantiopurities than Z and Fmoc protecting groups. Furthermore, a simple and efficient method for the synthesis of the medicinally interesting optically pure (R)-2- aminohexadecanol was developed.
Magrioti, Victoria,Fotakopoulou, Irene,Athinaios, Nicolaos,Anastasopoulou, Panoula,Constantinou-Kokotou, Violetta,Kokotos, George
scheme or table
p. 159 - 162
(2010/08/19)

Syntheis of new chiral 5,6,7,8-tetrahydrotetrazolo[1,5-a]pyrazines from α-amino acid derivatives following "click" chemistry
An efficient and practical synthesis of new chiral fused tetrazoles have been synthesized following [3+2] cycloaddition reaction starting from α-amino acid derivatives.
Mohapatra, Debendra K.,Maity, Pradip K.,Ghorpade, Ravindra V.,Gurjar, Mukund K.
body text
p. 865 - 872
(2010/09/16)

Amphoteric amino aldehydes reroute the Aza-Michael reaction
(Chemical Equation Presented) Amphoteric amino aldehydes, which exist as stable dimers, participate in an aza-Michael/aldol domino reaction with α,β-unsaturated aldehydes to afford stable 1,5-aminohydroxyaldehydes in high yields and diastereoselectivies.
Hili, Ryan,Yudin, Andrei K.
supporting information; experimental part
p. 16404 - 16406
(2010/02/15)

Synthesis of β-secretase inhibitors containing a hydroxyethylene dipeptide isostere
β-Secretase inhibitors with a Leu* Ala hydroxyethylene dipeptide (HED) isostere have been an especially interesting topic in recent years. In this study, a template compound 17 was synthesized, featuring truncation at the P2′ position and changes at P2 an
Yang, Xiaoming,Zou, Xiaomin,Fu, Yiqiu,Mou, Ke,Fu, Gang,Ma, Chao,Xu, Ping
p. 9 - 24
(2007/10/03)

Synthesis and evaluation of chloromethyl sulfoxides as a new class of selective irreversible cysteine protease inhibitors
The synthesis and biological evaluation of a new class of selective irreversible cysteine protease inhibitors is described. A set of amino acid based chloromethyl sulfoxides was prepared and they were found to inhibit irreversibly the cysteine protease papain. They were selective for cysteine proteases since no inhibition was found for the serine protease chymotrypsin.
Brouwer, Arwin J.,Bunschoten, Anton,Liskamp, Rob M.J.
p. 6985 - 6993
(2008/03/28)

Chemoenzymatic synthesis of enantiomerically enriched α-chiral 3-oxy-propionaldehydes by lipase-catalyzed kinetic resolution and desymmetrization
Enantiomerically enriched phenylalanine- and leucine aldehyde analogues have been prepared by lipase catalyzed desymmetrization or kinetic resolution of 1,3-propanediol derivatives as key steps. Observations of unusual enantioselectivity were made, and mo
Wiktelius, Daniel,Larsson, Emma K.,Luthman, Kristina
p. 2088 - 2100
(2007/10/03)

Arylaminoethyl amides as noncovalent inhibitors of cathepsin S. Part 2: Optimization of P1 and N-aryl
A systematic study of anilines led to the discovery of a metabolically robust fluoroindoline replacement for the alkoxy aniline toxicophore in 1. Investigations of the P1 pocket resulted in the discovery of a wide tolerance of functionality leading to the discovery of 11 as a potent and selective inhibitor of cathepsin S.
Alper, Phillip B.,Liu, Hong,Chatterjee, Arnab K.,Nguyen, Khanhlinh T.,Tully, David C.,Tumanut, Christine,Li, Jun,Harris, Jennifer L.,Tuntland, Tove,Chang, Jonathan,Gordon, Perry,Hollenbeck, Thomas,Karanewsky, Donald S.
p. 1486 - 1490
(2007/10/03)