cas 4465-44-5, N-Trityl-L-serine methyl ester

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Preparation method of 2,3-diamido methyl propionate
The invention provides a preparation method of 2,3-diamido methyl propionate. According to the method, serine is used as a raw material, in methyl alcohol, thionyl chloride is used as a catalyst for preparing serine methylester, then the serine methyleste
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Paragraph 0036; 0039; 0041

(2019/02/04)

MACROCYCLIC COMPOUNDS AS PROTEASOME INHIBITORS
The compounds of the present invention are represented by the following compounds having Formula I and Formula (I'): where the substituents R1, R2, R2', R3, R4, R5, R', R", X, Y, and Z are as defined herein and where the substituents R1, R2, R3, R4, R5, R', R", X, Y, and Z are as defined herein. These compounds are used in the treatment of bacterial infections, parasite infections, fungal infections, cancer, immunologic disorders, autoimmune disorders, neurodegenerative diseases and disorders, inflammatory disorders, or muscular dystrophy or for providing immunosuppression for transplanted organs or tissues.
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Paragraph 0507

(2019/05/02)

Highly Chemoselective Deprotection of the 2,2,2-Trichloroethoxycarbonyl (Troc) Protecting Group
Nonreducing, pH-neutral conditions for the selective cleavage of the 2,2,2-trichloroethoxycarbonyl (Troc) protecting group are reported. Using trimethyltin hydroxide in 1,2-dichloroethane, Troc-protected alcohols, thiols, and amines can be selectively unmasked in the presence of various functionalities that are incompatible with the reducing conditions traditionally used to remove the Troc group. This mild deprotection protocol tolerates a variety of other hydrolytically sensitive and acid/base-sensitive moieties as well.
Trost, Barry M.,Kalnmals, Christopher A.,Tracy, Jacob S.,Bai, Wen-Ju
supporting information
p. 8043 - 8046
(2019/01/04)

Activation of Remote meta-C?H Bonds in Arenes with Tethered Alcohols: A Salicylonitrile Template
Palladium-catalyzed activation of remote meta-C?H bonds in arenes containing tethered alcohols was achieved with high regioselectivity by using a nitrile template. Computational studies on the macrocyclic transition state of the regioselectivity-determini
Zhang, Lanlan,Zhao, Chaoyue,Liu, Yang,Xu, Jiancong,Xu, Xiufang,Jin, Zhong
supporting information
p. 12245 - 12249
(2017/09/06)

PHOSPHONATE COMPOUNDS FOR TREATMENT OF IMMUNE AND INFLAMMATORY DISORDERS
Compounds, methods of use, and processes for making inhibitors of complement Factor D are provided comprising Formula I, I" and I''' or a pharmaceutically acceptable salt or composition thereof. The inhibitors described herein target Factor D and inhibit
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Paragraph 0585

(2017/03/14)

Copper(I)-Mediated Denitrogenative Macrocyclization for the Synthesis of Cyclic α3β-Tetrapeptide Analogues
A copper(I)-mediated denitrogenative reaction has been successfully developed for the preparation of cyclic tetrapeptides. The key reactive intermediate, ketenimine, triggers intramolecular cyclization through attack of the terminal amine group to generate an internal β-amino acid with an amidine linkage. The chemistry developed herein provides a new synthetic route for the preparation of cyclic α3β-tetrapeptide analogues that contain important biological properties and results in rich structural information being obtained for conformational studies. With the success of this copper(I)-catalyzed macrocyclization, two histone deacetylase inhibitor analogues consisting of the cyclic α3β-tetrapeptide framework have been successfully synthesized.
Chen, Chun-Chi,Wang, Sheng-Fu,Su, Yung-Yu,Lin, Yuya A.,Lin, Po-Chiao
p. 1326 - 1337
(2017/06/23)

NOVEL COMPOUNDS
A compound of formula (I) or a pharmaceutically acceptable derivative thereof, (formula 1) wherein R1,R2, R3, R4, R5, X, m and n are defined in the specification; a process for preparing such compounds; a pharmaceutical composition comprising such compounds; and the use of such compounds in medicine.
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Page/Page column 101

(2016/02/26)

Facile and Versatile Chemoenzymatic Synthesis of Enterobactin Analogues and Applications in Bacterial Detection
Siderophores, such as enterobactin (Ent), are small molecules that can be selectively imported into bacteria along with iron by cognate transporters. Siderophore conjugates are thus a promising strategy for delivering functional reagents into bacteria. In this work, we present an easy-to-perform, one-pot chemoenzymatic synthesis of functionalized monoglucosylated enterobactin (MGE). When functionalized MGE is conjugated to a rhodamine fluorophore, which affords RhB-Glc-Ent, it can selectively label Gram-negative bacteria that utilize Ent, including some E. coli strains and P. aeruginosa. V. cholerae, a bacterium that utilizes linearized Ent, can also be weakly targeted. Moreover, the targeting is effective under iron-limiting but not iron-rich conditions. Our results suggest that the RhB-Glc-Ent probe is sensitive not only to the bacterial strain but also to the iron condition in the environment.
Lee, Albert A.,Chen, Yi -Chen S.,Ekalestari, Elisa,Ho, Sheng -Yang,Hsu, Nai -Shu,Kuo, Tang -Feng,Wang, Tsung -Shing Andrew
supporting information
p. 12338 - 12342
(2016/10/13)

Straightforward synthesis and antioxidant studies of chalcogenoaziridines
Herein we reported the synthesis of chalcogenoaziridines through the introduction of the organoselenium moiety in the aziridine framework through the nucleophilic substitution of the OTs leaving group. In addition, the antioxidant activity, as reflected b
Borges, Rodrigo,Andrade, Floyd C.D.,Schwab, Ricardo S.,Sousa, Fernanda S.S.,de Souza, Maurice Neto,Savegnago, Lucielli,Schneider, Paulo H.
supporting information
p. 3501 - 3504
(2016/07/15)

LMP7 INHIBITORS
The present disclosure provides compounds that are Large Multifunctional Protease 7 (LMP7) inhibitors and are therefore useful for the treatment of diseases treatable by inhibition of LMP7. Also provided are pharmaceutical compositions containing such compounds and processes for preparing such compounds.
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Page/Page column 48

(2016/04/26)

Methodology for Synthesis of Enantiopure 3,5-Disubstituted Pyrrol-2-ones
A new synthetic route towards chiral 3,5-disubstituted pyrrol-2-ones by starting from amino acids has been developed. The sequence features the conversion of amino acids into their corresponding alkynoic acid derivative followed by a Pd-catalyzed hydrosta
Krenk, Ondej,Kratochvl, Ji,pulk, Marcel,Buchta, Vladimr,Kune, Ji,Novkov, Lucie,Ghavre, Mukund,Pour, Milan
p. 5414 - 5423
(2015/08/24)

Studies on the synthesis of orthogonally protected azalanthionines, and of routes towards β-methyl azalanthionines, by ring opening of N-activated aziridine-2-carboxylates
Orthogonally protected azalanthionines were successfully synthesised by the ring-opening of N-activated aziridine-2-carboxylates with protected diaminopropanoic acids (DAPs). The required DAPs were also prepared by ring-opening of N-activated aziridine-2-carboxylates with para- methoxybenzylamine, but it was found that the choice of aziridine protecting groups dictated both the success of the reaction as well as the regioselectivity of the isolated products. Attempts to extend the methodology to the preparation of the more sterically demanding β-methyl azalanthionines have, so far, been unsuccessful.
O'Brien, Keith,ó Proinsias, Keith,Kelleher, Fintan
supporting information
p. 5082 - 5092
(2014/07/08)

Studies on the synthesis of orthogonally protected azalanthionines, and of routes towards β-methyl azalanthionines, by ring opening of N-activated aziridine-2-carboxylates
Orthogonally protected azalanthionines were successfully synthesised by the ring-opening of N-activated aziridine-2-carboxylates with protected diaminopropanoic acids (DAPs). The required DAPs were also prepared by ring-opening of N-activated aziridine-2-carboxylates with para-methoxybenzylamine, but it was found that the choice of aziridine protecting groups dictated both the success of the reaction as well as the regioselectivity of the isolated products. Attempts to extend the methodology to the preparation of the more sterically demanding β-methyl azalanthionines have, so far, been unsuccessful.
O'Brien, Keith,ó Proinsias, Keith,Kelleher, Fintan
supporting information
p. 5082 - 5092
(2014/12/10)

Synthesis of 1,2- trans -2-Acetamido-2-deoxyhomoiminosugars
The first synthesis of 1,2-trans-homoiminosugars devised as mimics of I-d-GlcNAc and I-d-ManNAc is described. Key steps include a regioselective azidolysis of a cyclic sulfite and a I-amino alcohol skeletal rearrangement applied to a polyhydroxylated azep
Blriot, Yves,Tran, Anh Tuan,Prencipe, Giuseppe,Jagadeesh, Yerri,Auberger, Nicolas,Zhu, Sha,Gauthier, Charles,Zhang, Yongmin,Dsir, Jrme,Adachi, Isao,Kato, Atsushi,Sollogoub, Matthieu
supporting information
p. 5516 - 5519
(2015/02/19)

Synthesis of nucleo aminooxy acid derivatives
Nucleobase-functionalized peptides have attracted increasing interest because of their well-ordered secondary structures and stability toward enzymatic degradations. We have designed and synthesized nucleo aminooxy acids as novel building blocks for nucle
Noel, Olivier,Xie, Juan
p. 134 - 140
(2013/03/13)

Process research for multikilogram production of etamicastat: A novel dopamine β-hydroxylase inhibitor
In order to develop a manufacturing route to etamicastat, three synthetic approaches to the pivotal chiral 3-aminochroman intermediate have been studied as well as four methods for the construction of the 2-aminoethyl imidazolethione fragment. The evoluti
Beliaev, Alexandre,Wahnon, Jorge,Russo, Domenico
scheme or table
p. 704 - 709
(2012/07/03)

Proteomic searches comparing two (R)-lacosamide affinity baits: An electrophilic arylisothiocyanate and a photoactivated arylazide group
We have advanced a novel strategy to search for lacosamide ((R)-1) targets in the brain proteome where protein binding is expected to be modest. Our approach used lacosamide agents containing "affinity bait" (AB) and "chemical reporter" (CR) units. The affinity bait moiety is designed to irreversibly react with the target, and the CR group permits protein detection and capture. In this study, we report the preparation and evaluation of (R)-N-(4-azido)benzyl 2-acetamido-3-(prop-2-ynyloxy)propionamide ((R)-3) and show that this compound exhibits potent anticonvulsant activities in the MES seizure model in rodents. We compared the utility of (R)-3 with its isostere, (R)-N-(4-isothiocyanato)benzyl 2-acetamido-3-(prop-2-ynyloxy)propionamide ((R)-2), in proteomic studies designed to identify potential (R)-1 targets. We showed that despite the two-fold improved anticonvulsant activity of (R)-3 compared with (R)-2, (R)-2 was superior in revealing potential binding targets in the mouse brain soluble proteome. The difference in these agents' utility has been attributed to the reactivity of the affinity baits (i.e., (R)-2: aryl isothiocyanate moiety; (R)-3: photoactivated aryl azide intermediates) in the irreversible protein modification step, and we conclude that this factor is a critical determinant of successful target detection where ligand (drug) binding is modest. The utility of (R)-2 and (R)-3 in in situ proteome studies is explored.
Park, Ki Duk,Stables, James P.,Liu, Rihe,Kohn, Harold
scheme or table
p. 2803 - 2813
(2010/08/21)

NOVEL N-BENZYLAMIDE SUBSTITUTED DERIVATIVES OF 2-(ACYLAMIDO)ACETIC ACID AND 2-(ACYLAMIDO)PROPIONIC ACIDS: POTENT NEUROLOGICAL AGENTS
A first aspect of the invention is a compound (sometimes also referred to herein as an "active agent" or "active compound") of Formula (I) or ( Ia): or a pharmaceutically acceptable salt or prodrug thereof. Compositions thereof and methods of using the same (e.g. for the treatment of a neurological disease) are also described.
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Page/Page column 27

(2009/12/27)

An enantiospecific approach to triazolylalanine derivatives
An efficient and practical route to an enantiomerically pure aziridinylmethyl azide is described that can be transformed to the corresponding triazole by a copper-catalysed [3+2] alkyne cycloaddition reaction. The transformation of these intermediates int
Jamookeeah, Clare E.,Beadle, Christopher D.,Harrity, Joseph P. A.
scheme or table
p. 133 - 137
(2009/06/18)

The in vitro transport of model thiodipeptide prodrugs designed to target the intestinal oligopeptide transporter, PepT1
A thiodipeptide carrier system is shown to be effective at enabling a range of covalently bound molecules, including benzyl, benzoyl and ibuprofen conjugates, to be transported via the intestinal peptide transporter PepT1, demonstrating its potential as a rational drug delivery target.
Foley, David,Pieri, Myrtani,Pettecrew, Rachel,Price, Richard,Miles, Stephen,Lam, Ho Kam,Bailey, Patrick,Meredith, David
supporting information; experimental part
p. 3652 - 3656
(2009/10/23)

Lacosamide isothiocyanate-based agents: Novel agents to target and identify lacosamide receptors
(R)-Lacosamide ((R)-2, (R)-N-benzyl 2-acetamido-3-methoxypropionamide) has recently gained regulatory approval for the treatment of partial-onset seizures in adults.Whole animal pharmacological studies have documented that (R)-2 function is unique. A robust strategy is advanced for the discovery of interacting proteins associated with function and toxicity of (R)-2 through the use of (R)-2 analogues, 3, which contain "affinity bait (AB)" and "chemical reporter (CR)" functional groups. In 3, covalent modification of the interacting proteins proceeds at the AB moiety, and detection or isolation of the selectively captured protein occurs through the bioorthogonal CR group upon reaction with an appropriate probe. We report the synthesis, pharmacological evaluation, and interrogation of the mouse soluble brain proteome using 3 where the AB group is an isothiocyanate moiety. One compound, (R)-N-(4-isothiocyanato)benzyl 2-acetamido-3-(prop-2-ynyloxy) propionamide ((R)-9), exhibited excellent seizure protection in mice, and like (R)-2, anticonvulsant activity principally resided in the (R)-stereoisomer. Several proteins were preferentially labeled by (R)-9 compared with (S)-9, including collapsin response mediator protein 2. 2009 American Chemical Society.
Ki, Duk Park,Morieux, Pierre,Salomé, Christophe,Cotten, Steven W.,Reamtong, Onrapak,Eyers, Claire,Gaskell, Simon J.,Stables, James P.,Liu, Rihe,Kohn, Harold
supporting information; experimental part
p. 6897 - 6911
(2010/04/24)

Oxinobactin, a siderophore analogue to enterobactin involving 8-hydroxyquinoline subunits: Synthesis and iron binding ability
Oxinobactin, a siderophore analogue to enterobactin but possessing 8-hydroxyquinoline instead of catechol complexing subunits, has been synthesized starting from l-serine and 8-hydroxyquinoline. Comparative iron binding studies showed that oxinobactin is as effective as enterobactin for the complexation of FeIII at physiological pH but with improved complexing ability at acidic pH.
du Moulinet d'Hardemare, Amaury,Alnaga, Nivine,Serratrice, Guy,Pierre, Jean-Louis
scheme or table
p. 6476 - 6478
(2009/10/01)

COMPOUNDS
This invention relates to new 6,8-difluorochroman-3-yl-1,3-dihydroimidazole-2-thiones, their preparation, and their use as a medicament.
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Page/Page column 22

(2008/12/07)

Synthesis of a homologous series of side-chain-extended orthogonally protected aminooxy-containing amino acids
Practical methodology is reported for the synthesis of a homologous series of side-chain-extended amino acids containing aminooxy functionality bearing orthogonal protection suitable for Fmoc peptide synthesis. These reagents may be useful for the preparation of libraries containing fragments joined by peptide linkers. Georg Thieme Verlag Stuttgart.
Liu, Fa,Thomas, Joshua,Burke Jr., Terrence R.
experimental part
p. 2432 - 2438
(2009/04/11)

First synthesis of N-[(aziridin-2-yl)methyl]benzimidazolequinone and analysis of toxicity towards normal and Fanconi anemia cells
A diazole is N-substituted with 1-trityl-2-methylaziridine and demethylated and oxidised with NBS under acidic conditions to give a benzimidazolequinone; this novel anti-tumour agent is marginally more cytotoxic than mitomycin C (MMC) towards the normal h
O'Donovan, Liz,Carty, Michael P.,Aldabbagh, Fawaz
scheme or table
p. 5592 - 5594
(2009/04/13)

Novel polymer-bound aminoalcohol ligands for the asymmetric addition of diethylzinc to aldehydes
The synthesis of several novel polymer-supported aziridine-containing aminoalcohol chiral ligands has been accomplished, and the polymers have been used as ligands for the catalytic asymmetric addition of diethylzinc to benzaldehyde, giving up to 89% ee. Incorporation onto a polymer support prevents the variation of ee with time that is observed in reactions of one unsupported ligand, perhaps as a result of site isolation of the ligand within the polymer, preventing cooperative effects. Copyright Taylor & Francis Group, LLC.
Page, Philip C. Bulman,Allin, Steven M.,Dilly, Suzanne J.,Buckley, Benjamin R.
p. 2019 - 2030
(2008/02/05)

Use of the Mitsunobu reaction in the synthesis of orthogonally protected α,β-diaminopropionic acids
Orthogonally protected α,β-diaminopropionic acids have been synthesised in good yields by the reaction of N-trityl l-serine esters with N-substituted sulfonamides under Mitsunobu reaction conditions (DEAD, PPh3, THF). The best isolated yields w
Kelleher, Fintan,Proinsias, Keith ó
p. 4879 - 4882
(2008/02/05)

(2,5-DIOXOIMIDAZOLIDIN-I-YL)-N-HYDROXY-ACETAMIDES AS METALLOPROTEINASE INHIBITORS
The invention provides compounds of the formula (I) wherein the variables are as defined in the specification. The compounds of the invention are inhibitors of metalloproteinase MMP-12 and are among other things useful for the treatment of obstructive air
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Page/Page column 51; 52

(2008/06/13)

Stereoselective syntheses of 4-oxa diaminopimelic acid and its protected derivatives via aziridine ring opening
Regio- and stereoselective aziridine ring opening with oxygen nucleophiles derived from serine and threonine provides a route to stereochemically pure 4-oxa-2,6-diaminopimelic acid (oxa-DAP) and its methyl-substituted derivatives. Oxa-DAP is a substrate of DAP epimerase, a key enzyme for biosynthesis of L-lysine and formation of peptidoglycan precursors. Orthogonally protected analogues of lanthionine and/β-methyllanthionine wherein oxygen replaces sulfur were prepared that could be used for solid-supported peptide synthesis to make oxa derivatives of lantibiotics.
Liu, Hongqiang,Pattabiraman, Vijaya R.,Vederas, John C.
p. 4211 - 4214
(2008/03/13)

SUBSTITUTED CHIRAL FUSED [1,2]IMIDAZO[4,5-C] RING COMPOUNDS
Substituted fused [1,2]imidazo[4,5-c] ring compounds (e.g., imidazo[4,5-c]quinolines, 6,7,8,9-tetrahydroimidazo[4,5-c]quinolines, imidazo[4,5-c]naphthyridines, and 6,7,8,9-tetrahydroimidazo[4,5-c]naphthyridines) with a -CH(-R1)- group in the fused ring at the 1-position of the imidazo ring, wherein Rl includes a functional group, for example, an amide, sulfonamide, urea, carbamate, ester, ketone, ether, a thio analog of the forgoing, sulfone, oxime, or hydroxylamine, pharmaceutical compositions containing the compounds, intermediates, methods of making the compounds, and methods of use of these compounds as immunomodulators, for inducing cytokine biosynthesis in animals and in the treatment of diseases including viral and neoplastic diseases, are disclosed.
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Page/Page column 141

(2008/06/13)

Total synthesis of the cytotoxic cyclopeptide mollamide, isolated from the sea squirt Didemnum molle
Full details of a total synthesis of the novel reverse prenyl substituted cyclic peptide mollamide, isolated from the ascidian Didemnum molle, are described.
McKeever, Benedict,Pattenden, Gerald
p. 2701 - 2712
(2007/10/03)

Stereochemical control in the preparation of α-amino N-methylthiazolidine masked aldehydes used for peptide aldehydes synthesis
Chiral N-methyl thiazolidines masked α-amino aldehydes are used for solid phase peptide aldehyde elongation. Contrary to N-Boc-protected α-amino aldehydes, N-trityl protection secures the chiral integrity of the incoming aldehyde chiral C1′ carbon atom du
Gros, Christel,Boulègue, Cyril,Galeotti, Nathalie,Niel, Gilles,Jouin, Patrick
p. 2673 - 2680
(2007/10/03)

A new and expeditious asymmetric synthesis of (R)- and (S)-2-aminoalkanesulfonic acids from chiral amino alcohols
The mechanism for the transformation of β-amino alcohol methanesulfonate hydrochlorides into sodium β-amino alkanesulfonates using sodium sulfite was investigated. The results show that sodium sulfite initially neutralizes the β-amino alcohol methanesulfonate hydrochloride to give a free β-amino alcohol methanesulfonate, which then cyclizes to a 2-alkylaziridine. Attack by the previously formed sodium bisulfite at the less hindered carbon atom of the aziridine ring then yields a β-amino alkanesulfate sodium salt. Based on this mechanistic proposal, a new and rapid asymmetric synthesis of (R)- and (S)-2-aminoalkanesulfonic acids from chiral amino alcohols was developed. Chiral amino alcohols were converted to chiral aziridines through the Wenker method or Mitsunobu reaction and the resulting aziridines were reacted with sodium bisulfite to produce chiral β-amino alkanesulfonic acids.
Xu, Jiaxi
p. 1129 - 1134
(2007/10/03)

Inhibitors or bone reabsorption and antagonists of vitronectin receptors
Novel inhibitors of bone reabsorption and antagonists of vitronectin receptors The present invention relates to 5-membered ring heterocycles of the formula I, in which E, F, G, W, Y and Z have the meaning given in the patent claims, to their preparation a
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(2008/06/13)

Stereospecific synthesis of functionalized ether phospholipids
A new stereospecific synthesis of functionalized alkyl ether phospholipids is reported. The synthesis is based upon the following: (1) the use of (R)-glycidyl tosylate as a chiral glycerol precursor; (2) the opening of a boron trifluoride catalyzed epoxide ring to introduce the functionalized sn-1-alkyl substituents; (3) the role of tetrahydropyranyl in protecting the sn-2-glycerol position; and (4) the elaboration of the sn-3-carbinol function, via the base hydrolysis of the acetoxy intermediate, obtained from the displacement of the toluenesulfonyl group of the substrate in dipolar aprotic media. Phosphorylation, using two different methods, has led to the development of two major classes of alkyllysophospholipids. For preparation of 'modulator-phospholipid' analogues, the substituted glycerol is coupled with 2,2,2-trichloro-tert-butyl phosphodichloridite and an N-protected amino acid ester, while elaboration of the phosphocholine headgroup of the target platelet-activating factor (PAF) analogues is achieved via the 2-chloro-2- oxo-1,3,2-dioxaphospholane/trimethylamine sequence. The synthesis provides rapid and efficient access to both types of phospholipids: (1) construction of the functionalized/substituted glycerol skeleton is achieved in a straightforward four-step sequence in better than 50% overall yield, and (2) phosphitylation or phosphorylation of the respective glycerol intermediates relies on reagents that require minimal use of protecting groups. The phospholipid compounds prepared include (1) the first synthetic analogue exhibiting modulator activity in conjunction with the glucocorticoid-receptor complex and (2) an sn-1-(ωamino)alkyl derivative of PAF, suitable for introduction of chain-terminal spectroscopic labels for biological and physicochemical studies to elucidate the mechanism of action of this highly potent alkyl ether phospholipid. The synthetic methods described herein have a great deal of flexibility, thus providing convenient general routes to a wide range of alkyl ether phospholipids.
Kazi, Abul B.,Shidmand, Sean,Hajdu, Joseph
p. 9337 - 9347
(2007/10/03)

High-yield synthesis of the enterobactin trilactone and evaluation of derivative siderophore analogs
A novel one-step synthesis of the macrocyclic triserine trilactone scaffold of the siderophore enterobactin, which eliminates the β-lactonization step of N-tritylserine, is presented. The cyclization reaction is based on a stannoxane template and leads to an overall yield of ~ 50%. This enables the practical functionalization of the trilactone by attaching chelating groups other than catecholamides. The conformational stability of the trilactone ring has been examined by high-resolution X-ray diffraction studies of the N-trityl intermediate: crystals grown from methylene chloride:methanol are orthorhombic, space group P212121 With unit cell dimensions a = 9.2495(5) A?, b = 11.3584(1) A?, c = 48.945(1) A?, V = 5142.1(2) A?3, and Z = 4. A hydroxypyridinonate analog of enterobactin, N,N',N''-tris[(3-hydroxy-1-methyl-2-oxo-(1H-pyridinyl)carbonyl]-4-cyclotriseryl trilactone (hopobactin), has been prepared by attachment of three 3-hydroxy-1-methyl-2(1H)-pyridinonate (3,2-HOPO) moieties to the triserine trilactone. This ligand represents the first enterobactin analog that retains the trilactone scaffold, but employs chelates other than catecholamides. Crystals of the chiral ferric complex grown from DMF:diethyl ether are monoclinic, space group P21, with unit cell dimensions a 13.0366(9) A?, b = 22.632(2) A?, c = 27.130(2) A?, b = 100.926(1)(o), V = 7860(1) A?3, and Z = 8. The Δ configuration of enterobactin metal complexes is also enforced in those of hopobactin and persists in aqueous or methanolic solution, as demonstrated by circular dichroism. The ferric hopobactin complex is the first reported chiral complex of hydroxypyridinonate ligands. The solution coordination chemistry of this new ligand and its iron(III) and iron(II) complexes have been studied by means of 1H NMR, potentiometric, spectrophotometric, and voltammetric methods. The average protonation constant of the hopobactin free ligand (log K(av) = 6.1) is typical of other 3-hydroxy-1-methyl-2-oxo-1H-pyridin-4-carboxamide ligands. The stability constants of the iron(III) complex formed with hopobactin (log β110 = 26.4) and with the tris(2-aminoethyl)amine-based analog, TRENHOPO, (log β110 to = 26.7) are of the same order of magnitude, unlike the catecholamide-based species, where enterobactin (log β110 = 49) is 6 orders of magnitude more stable than TRENCAM (log β110 = 43.6). The stability enhancement reflects the specific predisposition by the triserine scaffold of the catecholamide binding units. In spite of a significantly lower affinity of 3,2-hydroxypyridinonates for iron(III) compared with the more basic catecholates, hopobactin is an extraordinarily powerful chelating agent under acidic conditions: No measurable dissociation is observed even in 1.0 M HCl. In contrast to enterobactin and its synthetic derivatives, the hopobactin ferric complex undergoes no sequential protonation above pH 1. The affinity of hopobactin and TRENHOPO for iron(III) relative to iron(II) results in strongly negative reduction potentials, -782 mV vs 0.01 M Ag+/Ag in CH3CN or -342 mV vs NHE in water and -875 mV vs 0.01 M Ag+/Ag in CH3CN or -435 mV vs NHE in water, respectively.
Meyer,Telford,Cohen,White,Xu,Raymond
p. 10093 - 10103
(2007/10/03)

Efficient synthesis of (6R)-6-amino-1-methyl-4-(3-methylbenzyl)-hexahydro-1H-1,4-diazepine from methyl (2R)- and (2S)-1-benzyloxycarbonylaziridine-2-carboxylates
An efficient and practical method for the synthesis of (6R)-6-amino-1-methyl-4-(3-methylbenzyl)hexahydro-1H-1,4-diazepine 2, which serves as the amine part of DAT-582, a potent and selective 5-HT3 receptor antagonist, is described. The key inte
Kato, Shiro,Harada, Hiroshi,Morie, Toshiya
p. 3219 - 3225
(2007/10/03)

Synthesis of Amino Acids with Modified Principal Properties 2: Amino Acids with Polar Side Chains
The synthesis and characterization of five new homochiral amino acids derived from L-serine are presented.In the modified amino acids, the side chain of serine has been elongated by the introduction of one or more ethyleneoxy moieties and the new compounds contain either a terminal hydroxy group or a terminal amino group.Full experimental details are given for the synthesis of the following amino acids: (2S)-2-amino-6-hydroxy-4-oxahexanoic acid, (2S)-2-amino-9-hydroxy-4,7-dioxanonanoic acid, (2S)-2-amino-12-hydroxy-4,7,10-trioxadodecanoic acid, (2S)-2,9-diamino-4,7-dioxanonanoic acid, and (2S)-2,12-diamino-4,7,10-trioxadodecanoic acid.These compounds were prepared with a view to obtaining amino acids which possess physical and chemical properties such that their principal properties would be different from previously known amino acids.The structural modifications were made with the objective of altering the principal properties related both to lipophilicity and to size.The principal properties are determined as latent variables in the principal component analysis of molecular property descriptors.Three new amino acids, (2S)-2-amino-9-hydroxy-4,7-dioxanonanoic acid, (2S)-2-amino-12-hydroxy-4,7,10-trioxadodecanoic acid and (2S)-2,12-diamino-4,7,10-trioxadodecanoic acid were found to have principal properties which are clearly different from those of previously known amino acids.The principal properties as measured by the principal component scores are given.
Larsson, Ulf,Carlson, Rolf
p. 511 - 516
(2007/10/02)

Amino Acid Synthesis via Ring Opening of N-Sulphonyl Aziridine-2-Carboxylate Esters with Organometallic Reagents.
Nucleophilic ring opening of optically active N-sulphonyl aziridine-2-carboxylate esters with organometallic reagents has been investigated as a method of preparation of optically active amino acids.Key Words: aziridine-2-carboxylate, cuprate, nucleophilic ring opening, amino acid
Baldwin, Jack E.,Spivey, Alan C.,Schofield, Christopher J.,Sweeney, Joseph B.
p. 6309 - 6330
(2007/10/02)

L-aminodicarboxylic-(O-cycloalkyl)-L-aminocarboxylate alkyl ester sweeteners
Dipeptides of certain α-amino dicarboxylic acids and etherified hydroxy α-amino-mono-carboxylic acid esters possess a high order of sweetness. These dipeptides have the following formula: STR1 wherein R is alkyl containing 1-3 carbon atoms; R1
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(2008/06/13)

L-aminodicarboxylic acid amides of alkoxyalkylamines
The present invention is directed to new sweeteners of the formula: STR1 wherein, A is H, alkyl containing 1-3 carbon atoms, hydroxyalkyl containing 1-3 carbon atoms, alkoxymethyl wherein the alkoxy group contains 1-3 carbon atoms, or CO2 R in
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(2008/06/13)