cas 17342-08-4, L-Pyroglutaminol | Articles data

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INHIBITORS OF APOL1 AND METHODS OF USING SAME
The disclosure provides at least one entity chosen from compounds of formula (I), solid state forms of the same, compositions comprising the same, and methods of using the same, including use in treating focal segmental glomerulosclerosis (FSGS) and/or non-diabetic kidney disease (NDKD).
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(2020/07/14)

N-Heterocyclic carbene triazolium salts containing brominated aromatic motifs: Features and synthetic protocol
In this work, we provide a brief overview of the role of N-aryl substituents on triazolium N-heterocyclic carbene (NHC) catalysis. This synopsis provides context for the disclosed synthetic protocol for new chiral N-heterocyclic carbene (NHC) triazolium salts with brominated aromatic motifs. Incorporating brominated aryl rings into NHC structures is challenging, probably due to the substantial steric and electronic influence these substituents exert throughout the synthetic protocol. However, these exact characteristics make it an interesting N-aryl substituent, because the electronic and steric diversity it offers could find broad use in organometallic- A nd organo-catalysis. Following the synthetic reaction by NMR guided the extensive modification of a known protocol to enable the preparation of these challenging NHC pre-catalysts.
Raed, Anas Abo,Dhayalan, Vasudevan,Barkai, Shahar,Milo, Anat
p. 878 - 882
(2020/12/25)

Biphenyl compound as well as preparation method and medical application thereof
The invention discloses a biphenyl compound as well as a preparation method and medical application thereof, the structure of the biphenyl compound is shown as a formula (I) or a formula (II), and thebiphenyl compound or pharmaceutically acceptable salt, tautomer, meso-isomer, raceme, stereoisomer, metabolite, metabolite precursor, prodrug or solvate thereof is a PD-L1 inhibitor. The compound hasa remarkable inhibiting effect on the interaction of PD-1 and PD-L1 protein, so that the compound can be applied to the preparation of PD-L1 inhibitors and immunomodulator drugs for preventing or treating tumors, autoimmune diseases, organ transplant rejection, infectious diseases and inflammatory diseases.
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Paragraph 1517-1523

(2020/11/22)

Practical Synthesis of Chiral N-Heterocyclic Carbene Triazolium Salts Containing a Hydroxy Functional Handle
A library of functionalized chiral pyrrolidine-based N-heterocyclic carbene triazolium salts containing a hydroxy handle is prepared from readily accessible chiral (S)-pyroglutamic acid in eight steps. This improved synthetic protocol affords increased yields for known structures and 18 new NHCs are prepared by this method. The presence of a hydroxy handle offers potential for further functionalization and for non-covalent control over catalytic reactions in which the NHCs can serve as organocatalysts or ligands for organometallic catalysis.
Dhayalan, Vasudevan,Mal, Kanchan,Milo, Anat
p. 2845 - 2864
(2019/07/04)

5-HT7 Receptor Antagonists with an Unprecedented Selectivity Profile
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Ates, Ali,Burssens, Pierre,Lorthioir, Olivier,Lo Brutto, Patrick,Dehon, Gwenael,Keyaerts, Jean,Coloretti, Francis,Lallemand, Bénédicte,Verbois, Valérie,Gillard, Michel,Vermeiren, Céline
p. 795 - 802
(2018/04/02)

Discovery of Indolinone-Based Multikinase Inhibitors as Potential Therapeutics for Idiopathic Pulmonary Fibrosis
Idiopathic pulmonary fibrosis (IPF) is a serious and deadly disease for which treatment options are limited. The recent approval of antifibrosis agent nintedanib represents one of the first therapeutic approaches for the treatment of IPF. Here, we report novel indolinone-based multikinase inhibitors that target angiogenesis and fibrosis pathways and may serve as potential therapeutics for IPF. KBP-7018 is a novel, tyrosine kinase-selective inhibitor with potent effects on three fibrotic kinases (c-KIT, PDGFR, and RET). The pharmacokinetics (PK) properties of KBP-7018 were favorable in mice, rats, and dogs. In a bleomycin (BLM)-induced mouse pulmonary fibrosis model, 10, 30, and 100 mg/kg daily doses (q.d.) of KBP-7018 improved the 28-day survival rate in a dose-dependent manner. The improved efficacy of KBP-7018 compared to nintedanib provided a certain level of chemical validation for the involvement of PDGFR, c-KIT, and RET in IPF. Thus, KBP-7018 represents a novel multikinase inhibitor with differentiated activity, highly enhanced selectivity, and acceptable PK profiles that will enter phase I clinical trials.
Huang, Zhenhua,Li, Heran,Zhang, Qian,Lu, Fangzheng,Hong, Mei,Zhang, Zhigang,Guo, Xiaocui,Zhu, Yuanju,Li, Sanming,Liu, Hongzhuo
p. 1142 - 1147
(2017/11/15)

Compounding method for LCZ696 midbody
The invention discloses a compounding method for a LCZ696 midbody. The compounding route is as follows: wherein R1 is Me, Et or i-Pr; X is Cl, Br or I; R2 is Ms, Ts or Tf. According to the compounding method for the LCZ696 midbody disclosed by the invention, the methylating difficulty is reduced, the midbody is configured and overturned through the consequent reaction, the proportion of the required configuration is greatly increased, the product yield, purity and use ratio are increased and the industrial large-scale production is benefited.
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(2017/11/16)

Preparation method for L-hydroxyproline
The invention provides a preparation method for L-hydroxyproline. The preparation method comprises the following steps: preparing pyroglutamic acid; preparing pyroglutamate; preparing pyroglutamic acid alcohol; preparing (3R,7aS)-3-phenyltetrahydropyrrolo[1,2]oxazole-5(3H)-one; and preparing L-hydroxyproline. Compared with the prior art, the invention has the following beneficial effects: the method overcomes the problems that a traditional manner of extraction of L-hydroxyproline from an animal donor has potential safety hazards and that production of L-hydroxyproline is limited as biological raw materials are utilized, and can synthesize L-hydroxyproline under the condition of shortage of biological raw materials; synthetic methods for L-hydroxyproline are enriched; the added value of L-hydroxyproline is increased; the application scope of L-hydroxyproline can be further broadened; prepared L-hydroxyproline is high in yield and purity, so the synthesis purity of atazanavir is indirectly improved; and common raw materials can be selected in preparation of L-hydroxyproline, so production cost is low.
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(2016/10/10)

As tyrosine kinase inhibitors substituted indolinone derivatives
The invention belongs to the technical field of a medicine, and particularly relates to a substituted indole ketone derivative as a tyrosine kinase inhibitor shown in a general formula (I), a pharmaceutically acceptable salt, a deuterated article or a stereoisomer thereof, wherein R1, R2, R3, R4, R5, R6, R7, R8, Ra, Rb, Rc, Rd, n, n1, n2, n3, n4, a ring A and a ring B are defined in the specification. The invention also relates to a preparation method of the compound, a drug preparation containing the compound, and application of the compound in preparation of a drug for preventing or treating a fibrosis disease and treating an excessive hyperplasia disease.
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(2016/10/24)

CERTAIN PROTEIN KINASE INHIBITOR
Provided are certain CDK4/6 inhibitors, pharmaceutical compositions thereof, and methods of use therefor.
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Paragraph 184; 185

(2017/01/09)

CARBONITRILE DERIVATIVES AS SELECTIVE ANDROGEN RECEPTOR MODULATORS
The present invention relates to a compound of Formula 1, 2 or 3: I II III wherein A is N or -CR0--, where R0 is hydrogen, C1-C6 linear or branched chain alkyl, etc., Z is -CRe --, or, -N--, where Re is hydrogen, C1 -C6 linear or branched chain alkyl, etc.; R1 is hydrogen, C1 -C6 linear or branched chain alkyl, etc.; R2 are independently hydrogen or C1-C6 linear or branched chain alkyl; R3 and R4 are independently hydrogen, C1C6 linear or branched chain alkyl, etc.;. R5 and R6 are independently hydrogen or C1-C6 linear or branched chain alkyl, etc.; R8 is hydrogen, C1 -C6 linear or branched chain alkyl, etc.; R9 and R10 are independently hydrogen or C1- C6 linear or branched chain alkyl, etc.; Q is --CO--, --(CH2)q--, --(CHRs)q--, or -(CRsRt)q- -, where Rs and Rt are independently C1-C6 linear or branched chain alkyl, aryl, alkylaryl, heteroaryl or alkylheteroaryl; where q is 0, 1, 2, or 3; and, where n is 0, 1, 2, 3, 4 or 5; or, a pharmaceutically acceptable salt thereof, for the treatment of certain diseases, particularly those affected or mediated by the androgen receptor; to compbinations comprising such compounds with a second pharmaceutically active ingredient; to compositions containing such combinations; and to such combinations for the treatment of various diseases, particularly, those affected or mediated by the androgen receptor.
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(2015/12/17)

First total synthesis of oteromycin utilizing one-pot four-step cascade reaction strategy
The first total synthesis of oteromycin was investigated. Our previously reported convergent strategy for the synthesis of α-acyl-γ-hydroxy- γ-lactams was first applied for the total synthesis, however, the final deprotection of the methoxyaminal moiety could not be achieved since an unexpected intramolecular Diels-Alder (IMDA) reaction occurred. Therefore, a novel one-pot four-step cascade reaction starting from α-selenolactam was investigated. The efficient synthetic strategy was successfully developed to afford the desired oteromycin, and its complete structure elucidation including the stereochemistry at C24 position was also accomplished.
Uchiro, Hiromi,Shionozaki, Nobuhiro,Tanaka, Ryo,Kitano, Hiroyuki,Iwamura, Naoki,Makino, Kimiko
p. 506 - 511
(2013/02/23)

The fluorine-NHC gauche effect: A structural and computational study
Herein, we report the synthesis and X-ray structural analysis of a collection of fluorinated metal N-heterocyclic carbenes (Ag, Au, Pd, Rh, Ir) and their precursor salts. The common structural feature of these species is a flanking fluoroethyl group, which is either freely rotating or embedded within a bicyclic framework. Solid state analysis confirmed a gauche conformational preference in all cases with the fluorine adopting a syn clinal arrangement (φ[NCCF]～60°) with respect to the triazolium nitrogen at the vicinal position of the NHC. A density functional theory analysis was employed to quantify these effects and evaluate the influence of electronic modulation of the carbenic carbon [(CN+); neutral carbene (C:); metal-bound carbene (CM)], on the relative gauche/anti preference, thus highlighting the potential of this conformational phenomenon as a useful molecular design strategy for controlling the topology of organometallic complexes.
Paul, Susann,Schweizer, W. Bernd,Rugg, Graham,Senn, Hans Martin,Gilmour, Ryan
p. 5647 - 5659
(2013/07/11)

Straightforward synthesis of non-natural l-chalcogen and l-diselenide N-Boc-protected-γ-amino acid derivatives
The synthesis of new chiral seleno-, telluro-, and thio-N-Boc-γ-amino acids is described herein. These new compounds were prepared through a simple and short synthetic route, from the inexpensive and commercially-available amino acid l-glutamic acid. The products, with a highly modular character, were obtained in good to excellent yields, via hydrolysis of chalcogen pyroglutamic derivatives with overall retention of the l-glutamic acid stereochemistry. Also, an l-diselenide-N-Boc-γ-amino acid was prepared in good yield. This new synthetic route represents an efficient method for preparing new l-chalcogen- and l-diselenide-γ-amino acids with biological potential.
Kawasoko, Cristiane Y.,Foletto, Patricia,Rodrigues, Oscar E. D.,Dornelles, Luciano,Schwab, Ricardo S.,Braga, Antonio L.
p. 5173 - 5183
(2013/08/15)

Synthesis of new optically active 2-pyrrolidinones
A new class of optically active 2-pyrrolidinones was synthesized, starting from S-pyroglutamic acid, a well known natural chiral synthon. The synthetic design followed led to the insertion of various substituents at positions 1 and 5 of the 2-pyrrolidinone ring, including the imidazole moiety. Some of them possess two or three stereogenic centers, the configuration of which was retained under the mild conditions used. The new compounds also carry an imidazole moiety, which, along with the 2-pyrrolidinone template, may prove pivotal to several biological processes.
Moutevelis-Minakakis, Panagiota,Papavassilopoulou, Eleni,Mavromoustakos, Thomas
p. 50 - 73
(2013/03/14)

Synthesis, evaluation of anti-HIV-1 and anti-HCV activity of novel 2′,3′-dideoxy-2′,2′-difluoro-4′-azanucleosides
A series of 2′,3′-dideoxy-2′,2′-difluoro-4′- azanucleosides of both pyrimidine and purine nucleobases were synthesized in an efficient manner starting from commercially available L-pyroglutamic acid via glycosylation of difluorinated pyrrolidine derivative 15. Several 4′-azanucleosides were prepared as a separable mixture of α- and β-anomers. The 6-chloropurine analogue was obtained as a mixture of N 7 and N9 regioisomers and their structures were identified based on NOESY and HMBC spectral data. Among the 4′-azanucleosides tested as HIV-1 inhibitors in primary human lymphocytes, four compounds showed modest activity and the 5-fluorouracil analogue (18d) was found to be the most active compound (EC50 = 36.9 μM) in this series. None of the compounds synthesized in this study demonstrated anti-HCV activity.
Martínez-Montero, Saúl,Fernández, Susana,Sanghvi, Yogesh S.,Theodorakis, Emmanuel A.,Detorio, Mervi A.,McBrayer, Tamara R.,Whitaker, Tony,Schinazi, Raymond F.,Gotor, Vicente,Ferrero, Miguel
p. 6885 - 6893
(2013/01/15)

HEPATITIS C INHIBITOR COMPOUNDS
Compounds of Formula (I) and (II) wherein R1, R2, R3, R6, A and A' are defined herein. The compounds are useful as inhibitors of the function of NS5A protein encoded by HCV for the treatment of hepatitis C viral infection.
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(2012/05/04)

STRUCTURAL MIMETICS OF PROLINE-RICH PEPTIDES AND THE PHARMACEUTICAL USE THEREOF
The invention relates to compounds of general formula (I), which can be used particularly as structural mimetics of proline-rich peptides and are therefore capable of binding PRM binding domains (proline-rich motif binding domains) of proteins. The invention also relates to the use of said compounds as pharmaceutical active agents and the use of these pharmaceutical active agents for treating bacterial diseases, neurodegenerative diseases and tumours.
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(2011/02/26)

Synthesis, in silico docking experiments of new 2-pyrrolidinone derivatives and study of their anti-inflammatory activity
A new class of 2-pyrrolidinone derivatives was designed, synthesized, and tested for their antioxidant and anti-inflammatory activities. The compounds were evaluated for their inhibitory activity against LOX. The most potent among them, 14d [IC50 0.08 (±0.005) mM], and 14e [IC50 0.0705 (±0.003) mM], were also tested in vivo. The compound 14d induced equipotent inhibition against rat paw edema, which is very close to the effect produced by the commonly used standard, namely indomethacin (47%). The LOX inhibitory activity of the compound 14e proceeds in parallel to the % inhibitory value of lipid peroxidation meaning that this LOX inhibitory activity is supported by the lipid peroxidation inhibition. The molecular features that govern their bioactivity were explored through in silico docking experiments. The results showed that acidic moieties must be placed in certain distance and orientation in the active site of LOX enzyme in order to productively exhibit inhibitory activity. In addition, the 2-pyrrolidinone template significantly contributes in the inhibitory properties of the new compounds.
Moutevelis-Minakakis, Panagiota,Papavassilopoulou, Eleni,Michas, George,Georgikopoulou, Kalliopi,Ragoussi, Maria-Eleni,Neophytou, Niki,Zoumpoulakis, Panagiotis,Mavromoustakos, Thomas,Hadjipavlou-Litina, Dimitra
p. 2888 - 2902
(2011/06/17)

Asymmetric transfer hydrogenation of aromatic ketones using rhodium complexes of chiral N-heterocyclic carbenes derived from (S)-pyroglutamic acid
A new and flexible procedure for the preparation of chiral azolium salts derived from (S)-pyroglutamic acid has been developed. The efficiency of these ligands has been evaluated in the metal-catalyzed asymmetric transfer hydrogenation of aromatic ketones in isopropanol. Good enantioselectivities up to 90%ee were observed.
Aupoix, Audrey,Bournaud, Chloee,Vo-Thanh, Giang
p. 2772 - 2776
(2011/06/23)

Remote chiral induction in vinyl sulfonium salt-mediated ring expansion of hemiaminals into epoxide-fused azepines
The planet of the azepines: Epoxy-fused azepines have been synthesized in a highly selective reaction with hemiaminals and vinyl sulfonium salts. Stereochemistry is controlled by the substituent at the four- or five-position of the hemiaminal. The key step involves ring-opening of the hemiaminal, conjugate addition onto a vinyl sulfonium salt, and epoxidation of the aldehyde by the in situ formed sulfur ylide. Copyright
Yar, Muhammad,Unthank, Matthew G.,McGarrigle, Eoghan M.,Aggarwal, Varinder K.
p. 372 - 375
(2011/10/09)

Late-stage diversification of chiral N-heterocyclic-carbene precatalysts for enantioselective homoenolate additions
A library of chiral triazolium salts has been prepared by late-state diversification of a triazolium amine salt. By utilizing a primary amine as a functional handle, a single triazolium salt can be transformed into a variety of chiral N-heterocyclic carbene precatalysts. This approach makes the preparation of chiral N-heterocyclic carbenes possible by a single-step modification of a triazolium salt, rather than the usual need for multistep organic synthesis and challenging heterocycle formation for each member of a catalyst library. We have screened these catalysts for control of diastereo- and enantioselectivity in a γ-lactam-forming reaction between α,β-unsaturated aldehydes and cyclic ketimines. Saving the best for last: Enantioselective homoenolate additions have been hindered by the challenge of synthesizing N-mesityl-substituted azolium salts. A library of pyrrole-functionalized chiral triazolium salts was prepared by direct modification of the preformed azolium core. Copyright
Zheng, Pinguan,Gondo, Chenaimwoyo A.,Bode, Jeffrey W.
scheme or table
p. 614 - 620
(2011/10/12)

Synthesis of 3-guaninyl- and 3-adeninyl-5-hydroxymethyl-2-pyrrolidinone nucleosides
l- And d-glutamic acids, as well as trans-4-hydroxy-l-proline, are converted to the corresponding 3-guaninyl-5-hydroxymethyl-2-pyrrolidinone (4) or 3-adeninyl-5-hydroxymethyl-2-pyrrolidinone (5) nucleoside analog. The protecting group used to block the lactam nitrogen in key intermediates has a significant effect on the diastereoselectivity of the coupling reaction with adenine or guanine.
Saleh, Abdullah,D'Angelo, John G.,Morton, Martha D.,Quinn, Jesse,Redden, Kendra,Mielguz, Rafal W.,Pavlik, Christopher,Smith, Michael B.
scheme or table
p. 5574 - 5583
(2011/10/02)

Synthesis of chiral bifunctional (Thio)urea n-heterocyclic carbenes
The rapid and modular synthesis of the first bifunctional N-heterocyclic carbenes bearing a (thio)urea moiety as H-bond donor group was reported. Different analogues could be accessed in seven steps from cheap (S)-pyroglutamic acid in good overall yields (14-30%). The synthesized carbenes were active catalysts in the benzoin reaction. Georg Thieme Verlag Stuttgart - New York.
Brand, Jonathan P.,Siles, José Ignacio Osuna,Waser, Jér?me
supporting information; experimental part
p. 881 - 884
(2010/07/10)

Addressing protein-protein interactions with small molecules: A pro-pro dipeptide mimic with a PPII helix conformation as a module for the synthesis of PRD-binding ligands
X marks the spot: The synthetic tricyclic amino acid X (see structure; C gray, H cyan, N blue, O red, double bond yellow) can be incorporated, without loss of binding ability, as a Pro-Pro substitute into two peptides that bind to the proline-rich motif-recognizing domains Fyn-SH3. The dipeptide analogue X, which is locked in a polyproline type II helix conformation, is created by stereoselective introduction of a vinylidene bridge into a diproline unit.
Zaminer, Jan,Brockmann, Christoph,Huy, Peter,Opitz, Robert,Reuter, Cedric,Beyermann, Michael,Freund, Christian,Mueller, Matthias,Oschkinat, Hartmut,Schmalz, Hans-Guenther,Kuehne, Ronald
supporting information; experimental part
p. 7111 - 7115
(2010/12/18)

Functionalized pyrrolidine inhibitors of human type II α-mannosidases as anti-cancer agents: Optimizing the fit to the active site
Refining the chemical structure of functionalized pyrrolidine-based inhibitors of Golgi α-mannosidase II (GMII) to optimize binding affinity provided a lead molecule that demonstrated nanomolar competitive inhibition of α-mannosidases II and an optimal fit in the active site of Drosophila GMII by X-ray crystallography. Esters of this lead compound also inhibited the growth of human glioblastoma and brain-derived endothelial cells more than the growth of non-tumoral human fibroblasts, suggesting their potential for anti-cancer therapy.
Fiaux, Helene,Kuntz, Douglas A.,Hoffman, Daniela,Janzer, Robert C.,Gerber-Lemaire, Sandrine,Rose, David R.,Juillerat-Jeanneret, Lucienne
p. 7337 - 7346
(2008/12/23)

New chiral diamide ligands: synthesis and application in allylic alkylation
A new family of chiral diamide ligands has been designed and synthesised. These ligands have been successfully applied to an asymmetric allylic substitution reaction. A palladium complex of one of the diamide ligands achieved enantioselectivities of up to 93% in the allylic alkylation of 1,3-diphenyl-3-acetoxyprop-1-ene.
Bateman, Lorraine,Breeden, Simon W.,O'Leary, Patrick
p. 391 - 396
(2008/09/19)

An optimised synthetic approach to a chiral derivatising agent and the utilisation of a dimerisation reaction in the synthesis of a novel C2-symmetric diphosphine ligand
We report an optimised synthetic approach to the chiral derivatising agent (5R)-methyl-1-(chloromethyl)-2-pyrrolidinone. In addition, the observation of an unwanted dimerisation product is turned to our advantage by providing a method for the synthesis of a new class of C2-symmetric chiral diphosphine.
Williams, Glynn D.,Wade, Charles E.,Clarkson, Guy J.,Wills, Martin
p. 664 - 670
(2007/10/03)

Stereoselective conjugate addition of lactams to nitroalkenes and formal total synthesis of indolizidine 167B
Optically active 5-substituted pyrrolidin-2-ones underwent conjugate addition to nitroalkenes to give the corresponding adducts in a diastereoselective manner. The presence of 18-crown-6 was crucial to achieve good stereoselective addition. Addition of 6-substituted piperidin-2-ones also gave the corresponding adduct in a stereoselective manner. The adduct was readily converted into a bicyclic lactam through intramolecular nitroaldol reaction, and the formal synthesis of indolizidine 167B was achieved.
Kamimura, Akio,Nagata, Yoshiaki,Kadowaki, Ayako,Uchida, Kosuke,Uno, Hidemitsu
p. 11856 - 11861
(2008/03/13)

Copper(I) mediated cross-coupling of amino acid derived organozinc reagents with acid chlorides
This paper describes the development of a straightforward experimental protocol for copper-mediated cross-coupling of amino acid derived β-amido-alkylzinc iodides 1 and 3 with a range of acid chlorides. The present method uses CuCN·2LiCl as the copper source and for organozinc reagent 1 the methodology appears to be limited to reaction with more stable acid chlorides, providing the desired products in moderate yields. When applied to organozinc reagent 3, however, the protocol is more general and provides the products in good yields in all but one of the cases tested. The Royal Society of Chemistry 2006.
Hjelmgaard, Thomas,Tanner, David
p. 1796 - 1805
(2008/02/05)

Asymmetric intramolecular crossed-benzoin reactions by N-heterocyclic carbene catalysis
(Chemical Equation Presented) Getting cross: Excellent asymmetric inductions and very good yields are achieved in the generation of a quaternary stereocenter in α-hydroxy-substituted tetralones by using chiral N-heterocyclic carbene catalysts in an enantioselective intramolecular crossed-benzoin reaction. The synthesis of the corresponding α-hydroxyindanones with good ee values is also possible by this route.
Enders, Dieter,Niemeier, Oliver,Balensiefer, Tim
p. 1463 - 1467
(2007/10/03)

A unified synthetic strategy toward oroidin-derived alkaloids premised on a biosynthetic proposal
Details of the evolution of a synthetic strategy toward the spirocyclic chlorocyclopentane core of oroidin-derived alkaloids, including the axinellamines and potentially adaptable to palau'amine, are described. A proposed refinement of the Kinnel-Scheuer biosynthetic proposal for palau'amine is posited. Studies undertaken to improve the regioselectivity and efficiency of a key Diels-Alder reaction utilizing a novel protecting group strategy, microwave chemistry, and other strategies are described. Further insights regarding the suitability of different protecting groups during the epoxidation/chlorination/ring contraction sequence are disclosed. Several interesting by-products from this reaction sequence are reported. These studies have led to a unified synthetic strategy to the axinellamines and palau'amine.
Dransfield, Paul J.,Dilley, Anja S.,Wang, Shaohui,Romo, Daniel
p. 5223 - 5247
(2007/10/03)

ALTERNATIVE SYNTHESIS OF RENIN INHIBITORS AND INTERMEDIATES THEREOF
The present invention relates to synthetic routes to prepare a compound of the formula (A); wherein R1 is halogen, C1-6 halogenalkyl, C1-6 alkoxy-C1-6 alcoxy or C1-6alkoxy-C1-6alkyl; R2 is halogen, C1-4alkyl or C1-4alkoxy; R3 and R4 are independently branched C3-6alkyl; and R5 is cycloalkyl, C1-6alkyl, C1-6hydroxyalkyl, Cl-6alkoxy-C 1-6alkyl, C1-6alkanoyloxy-C1-6alkyl, C1-6aminoalkyl, C1-6alkylamino-C 1-6alkyl, Cl-6dialkylamino-C1-6alkyl, C1-6alkanoylamino- C1-6alkyl, HO(O)C-Cl-6alkyl, C1-6alkyl-O-(O)C-C1-6alkyl, H2N-C(O)-Cl-6alkyl, C1-6alkyl-HN-C(O)-C1-6alkyl or (C1-6alkyl)2N-C(O)-C1-6alkyl; or a pharmaceutically acceptable salt thereof as well as key intermediates obtained when following these routes as well as their preparation.
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Page/Page column 36; 37

(2010/10/20)

An enantioselective total synthesis of (-)-stemoamide
An enantioselective synthesis of (-)-stemoamide has been achieved in 14 steps starting from pyroglutamyl alcohol in ca. 7% overall yield. The key steps in the strategy are a conjugate addition of a vinyl copper reagent and a ring closing metathesis (RCM) reaction to form the seven-membered ring.
Sibi, Mukund P.,Subramanian, Thangaiah
p. 1211 - 1214
(2007/10/03)

Stereoselective synthesis of trans-threo-trans-oligopyrrolidines: Potential agents for RNA cleavage
The 2,5-trans-substituted oligopyrrolidines constitute a promising class of novel RNA-binding agents as well as potential building blocks for artificial anion channels. A convergent synthesis of terpyrrolidine 1 and pyrrolidino-THF-pyrrolidine 2 is reported, relying upon convergent coupling of 2,5-trans-pyrrolidinecarboxaldehydes through bridging alkyne units under Felkin-Anh control and subsequent closure of the central ring. After complete deprotection, the free polyamine products were isolated in excellent yield and purity. Crystal structure analyses of a terpyrrolidine and a pyrrolidino-THF-pyrrolidine documented their helical privileged conformations. The compounds were then screened for RNA cleavage activity. Unlike the only weakly active simple polyamines, p-nitrosulfonamide 33 was found to induce cleavage at mM concentrations under physiologically relevant conditions.
Arndt, Hans-Dieter,Welz, Ruediger,Mueller, Sabine,Ziemer, Burkhart,Koert, Ulrich
p. 3945 - 3962
(2007/10/03)

Process for chemical reaction of amino acids and amides yielding selective conversion products
The invention relates to processes for converting amino acids and amides to desirable conversion products including pyrrolidines, pyrrolidinones, and other N-substituted products. L-glutamic acid and L-pyroglutamic acid provide general reaction pathways to numerous and valuable selective conversion products with varied potential industrial uses.
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Page 6-7

(2008/06/13)

Synthesis and utility of the 3,3-dimethyl-5-substituted-2-pyrrolidinone 'Quat' chiral auxiliary
The synthesis and utility of the 3,3-dimethyl-5-substituted-2-pyrrolidinone 'Quat' chiral auxiliary in stereoselective enolate reactions of attached N-acyl side chains combined with the mild and non-racemising conditions required for the ultimate removal of the chiral side chain is described.
Davies, Stephen G.,Dixon, Darren J.,Doisneau, Gilles J.-M.,Prodger, Jeremy C.,Sanganee, Hitesh J.
p. 647 - 658
(2007/10/03)

Efficient synthesis of (S)-3,4-dihydro-2-pivaloyloxymethyl-2H-pyrrole 1-oxide
A convenient synthesis of the title nitrone is reported. The sequence starts from ethyl L-pyroglutamate as the source of chirality and the key step is the generation of an unstable α-methoxy-N-carboxylate ion, which readily decomposes to an imine. The oxidation of the imine with methyl(trifluoromethyl)dioxirane provides the enantiopure nitrone, which is trapped with dimethyl acetylenedicarboxylate.
Busque, Felix,De March, Pedro,Figueredo, Marta,Font, Josep,Gallagher, Timothy,Milan, Sergio
p. 437 - 445
(2007/10/03)

Catalytic Hydrogenation of Chiral α-Amino and α-Hydroxy Esters at Room Temperature with Nishimura Catalyst without Racemization
The hydrogenation of carboxylic acid derivatives at room temperature was investigated. With a mixed Rh/Pt oxide (Nishimura catalyst), low to medium activity was observed for various α-amino and α-hydroxy esters. At 100 bar hydrogen pressure and 10% catalysts loading, high yields of the desired amino alcohols and diols were obtained without racemization. The most suitable α-substituents were NH2, NHR, and OH, whereas β-NH2 were less effective. Usually, aromatic rings were also hydrogenated, but with the free bases of amino acids as substrates, some selectivity was observed. No reaction was found for α-NR2, α-OR, and unfunctionalized esters; acids and amides were also not reduced under these conditions. A working hypothesis for the mode of action of the catalyst is presented.
Studer, Martin,Burkhardt, Stefan,Blaser, Hans-Ulrich
p. 802 - 808
(2007/10/03)

Synthesis of optically active functionalised cyclic ketimines and their application in enantioselective catalysis
The synthesis of enantiomerically pure cyclic ketimines attached to moieties containing additional donor atoms is described. The resulting optically active chelating ligands are tested in the rhodium-catalysed enantioselective hydrosilylation of acetophenone with respect to their inductive potential.
Graf v. Keyserlingk, Nikolai,Martens, Juergen
p. 2213 - 2222
(2007/10/03)

Diastereoselective formation of a quaternary center in a pyroglutamate derivative. Formal synthesis of Monatin
In this communication we describe a highly diastereoselective formation of a quaternary center present in the structure of Monatin, a potent sweetening agent isolated from natural sources. The synthesis of a derivative useful for biological studies on the interactions of this type of sweetening substance on taste receptors is described. The strategy relies on the oxidation of an enolate originating from a pyroglutamate derivative followed by a highly diastereoselective alkylation with an electrophile obtained from indole.
Oliveira, Davi De Jesus,Coelho, Fernando
p. 6793 - 6796
(2007/10/03)

Synthesis and analysis of the sterically constrained L-glutamine analogues (3S,4R)-3,4-dimethyl-L-glutamine and (3S,4R)-3,4-dimethyl-L-pyroglutamic acid
The nonproteinogenic amino acids (3S,4R)-3,4-dimethyl-L-pyroglutamic acid and (3S,4R)-3,4-dimethyl-L-glutamine - found in the cyclic depsipeptides callipeltin B, callipeltin A, and papuamide A - were synthesized from a common intermediate derived from L-pyroglutamic acid. The diastereoselective introduction of the methyl groups was accomplished by cuprate addition and enolate alkylation, followed by a kinetic epimerization of the C-4 methyl substituent. (3S,4R)-3,4-Dimethyl-L-glutamine shows a conformational restriction of its side chain which may be related to its biological function in the natural products where it is found.
Acevedo, Cristina M,Kogut, Eugene F,Lipton, Mark A
p. 6353 - 6359
(2007/10/03)

A facile entry to bicyclic systems from L-glutamic acid
An efficient synthesis of bicyclic heterocycles has been realized from L-glutamic acid. The key step is the construction of the pyrrole ring in a single step, using tosylmethyl isocyanide (TosMIC) methodology. Structures of reaction intermediates and final products were investigated using density functional theory calculations.
Frieman, Bryan A.,Bock, Charles W.,Bhat, Krishna L.
p. 2099 - 2108
(2007/10/03)

Highly diastereoselective alkylation of a pyroglutamate derivative with an electrophile obtained from indole. Synthesis of a potential intermediate for the preparation of the natural sweetener (-)-Monatin
The synthesis of a potential intermediate for the preparation of the very intensive sweetening agent (-)-Monatin is described. The synthesis is based on a highly diastereoselective alkylation reaction of a pyroglutamate derivative with an electrophile obtained from indole.
Oliveira, Davi De Jesus,Coelho, Fernando
p. 2143 - 2159
(2007/10/03)

Synthesis of amino alcohol derivatives from (L)-pyroglutamic acid on solid-phase
A procedure for the solid phase synthesis of optically active substituted N-tosyl amines from the corresponding N-tosyl lactams has been developed. A variety of N-tosyl amines were synthesized by ring-opening of N- tosyl lactams by various nucleophiles such as alkoxides, amines or Grignard reagents.
Cossy, Janine,Tresnard, Ludovic,Gomez Pardo, Domingo
p. 409 - 411
(2007/10/03)

Total synthesis of (+)-calyculin A and (-)-calyculin B: Cyanotetraene construction, asymmetric synthesis of the C(26-37) oxazole, fragment assembly, and final elaboration
A convergent total synthesis leading to (+)-calyculin A and (-)-calyculin B (1 and 2), antipodes of the potent, highly selective and remarkably cell-permeable phosphatase inhibitors calyculins A and B, has been achieved. In the preceding paper we outlined the asymmetric synthesis of the C(9-25) spiroketal dipropionate subunit (+)-BC; herein we describe construction of the C(1-8) cyanotetraene, an asymmetric synthesis of the C(26-37) oxazole, fragment assembly and final elaboration to (+)-1 and (-)-2. Highlights of the synthesis include: application of a one-pot three-component Suzuki reaction for the construction of phosphonate A, a bifunctional triene precursor of the light sensitive C(1-8) cyanotetraene subunit, an asymmetric synthesis of the C(26-32) oxazole (-)-D, exploiting the Silks-Odom 77Se NMR protocol to assess enantiomeric purity, construction of the C(33-37) subtarget (-)-E in a highly stereocontrolled fashion via an acyliminium ion, and a concise, highly efficient sequence for fragment assembly and elaboration to (+)-calyculin A and (-)-calyculin B. The synthesis of (-)-2 also confirms the structure of calyculin B, previously based only on spectral comparison with calyculin A.
Smith III, Amos B.,Friestad, Gregory K.,Barbosa, Joseph,Bertounesque, Emmanuel,Duan, James J.-W.,Hull, Kenneth G.,Iwashima, Makoto,Qiu, Yuping,Spoors, P. Grant,Salvatore, Brian A.
p. 10478 - 10486
(2007/10/03)

Approaches to a synthesis of α-kainic acid
A formal synthesis of (-)-α-kainic acid was achieved from L- pyroglutamic acid. The C-4 substituent of the pyrrolidine ring was introduced by using a ketyl radical cyclization on an ene carbamate.
Cossy, Janine,Cases, Manuel,Pardo, Domingo Gomez
p. 6153 - 6166
(2007/10/03)

Fleming-Tamao oxidation and masked hydroxyl functionality: Total synthesis of (+)-pramanicin and structural elucidation of the antifungal natural product (-)-pramanicin
The total synthesis of (+)-pramanicin (41b) is reported, thereby establishing the relative and absolute stereochemistry of the naturally occurring antifungal agent. The key steps involve (i) conjugate addition of the diethyl((diethylamino)diphenylsilyl)zincate to a suitably protected γ- lactam 3 and quenching of the resultant enolate with the α,β-unsaturated γ,δ-epoxy aldehyde 2 (X = H), (ii) Ni(acac)2-catalyzed hydroxylation of a β-dicarbonyl array, and (iii) Fleming-Tamao oxidation to reveal the masked C-3 hydroxyl group.
Barrett, Anthony G. M.,Head, John,Smith, Marie L.,Stock, Nicholas S.,White,Williams
p. 6005 - 6018
(2007/10/03)

A formal synthesis of (-)-α-kainic acid
The formal synthesis of (-)-α-kainic acid was achieved from L-pyroglutamic acid. The C-4 substituent of the pyrrolidine ring was introduced by using a ketyl radical cyclization on an enecarbamate.
Cossy, Janine,Cases, Manuel,Gomez Pardo, Domingo
p. 507 - 509
(2007/10/03)

Stereoselective synthesis of a terpyrrolidine unit, a potential building block for anion recognition
The first stereoselective synthesis of a trans-threo-trans-threo-trans terpyrrolidine was achieved. A bidirectional strategy involving double acetylide coupling of two trans-N-BOC-pyrrolidine-aldehydes 3, epimerisation-free hydrogenation and ring closure via a seven-membered cyclic sulfate gives access to the terpyrrolidine scaffold.
Arndt, Hans-Dieter,Polborn, Kurt,Koert, Ulrich
p. 3879 - 3882
(2007/10/03)