cas 7149-65-7, Ethyl L-pyroglutamate | Articles data

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Studies towards the total synthesis of Batzelladine A: Synthesis of a model pyrrolo[1,2-c]pyrimidine
A new approach to the synthesis of fragments related to the batzelladine alkaloids has been developed using a formal asymmetric aza-Diels-Alder reaction.
Elliott, Mark C.,Long, Matthew S.
p. 9191 - 9194
(2002)
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IMPROVED PROCESS FOR THE PREPARATION OF (2S)-N-{(1S)-1-(2-CHLOROPHENYL)-2-[(3,3-DIFLUOROCYCLOBUTYL)-AMINO]-2-OXOETHYL}-1-(4-CYANOPYRIDIN-2-YL)-N-(5-FLUOROPYRIDIN-3-YL)-5-OXOPYRROLIDINE-2-CARBOXAMIDE
The present invention relates to improved process for the preparation of (2S)-N-{(1S)-1-(2-chlorophenyl)-2-[(3,3-difluorocyclobutyl)-amino]-2-oxoethyl}-1-(4-cyanopyridin-2-yl)-N-(5-fluoropyridin-3-yl)-5-oxopyrrolidine-2-carboxamide and its pharmaceutically acceptable salts represented by the following structural formula. Formula-1 The present invention relates to novel intermediates useful in the preparation of Ivosidenib of formula-1 and novel process for the preparation of (2S)-N-{(1S)-1-(2-chlorophenyl)-2-[(3,3-difluorocyclobutyl)-amino]-2-oxoethyl}-1-(4-cyanopyridin-2-yl)-N-(5-fluoropyridin-3-yl)-5-oxopyrrolidine-2-carboxamide. The present invention also relates to solid state forms of (2S)-N-{(1S)-1-(2-chlorophenyl)-2-[(3,3-difluorocyclobutyl)-amino]-2- oxoethyl}-1-(4-cyanopyridin-2-yl)-N-(5-fluoropyridin-3-yl)-5-oxopyrrolidine-2-carboxamide.
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Page/Page column 29-30

(2021/04/30)

INHIBITORS OF HISTONE DEACETYLASE USEFUL FOR THE TREATMENT OR PREVENTION OF HIV INFECTION
The present invention relates to Compounds of Formula (I): Formula (I) and pharmaceutically acceptable salts or prodrug thereof, wherein R1, R2, R3, Ra, Rb, A and B are as defined herein. The present invention also relates to compositions comprising at least one compound of Formula (I), and methods of using the compounds of Formula (I) for treating or preventing HIV infection in a subject.
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Page/Page column 29

(2020/02/23)

Discovery and Development of 3-(6-Chloropyridine-3-yloxymethyl)-2-azabicyclo[3.1.0]hexane Hydrochloride (SUVN-911): A Novel, Potent, Selective, and Orally Active Neuronal Nicotinic Acetylcholine α4β2 Receptor Antagonist for the Treatment of Depression
A series of chemical optimizations guided by in vitro affinity at the α4β2 receptor in combination with selectivity against the α3β4 receptor, pharmacokinetic evaluation, and in vivo efficacy in a forced swim test resulted in identification of 3-(6-chloropyridine-3-yloxymethyl)-2-azabicyclo[3.1.0]hexane hydrochloride (9h, SUVN-911) as a clinical candidate. Compound 9h is a potent α4β2 receptor ligand with a Ki value of 1.5 nM. It showed >10 μM binding affinity toward the ganglionic α3β4 receptor apart from showing selectivity over 70 other targets. It is orally bioavailable and showed good brain penetration in rats. Marked antidepressant activity and dose-dependent receptor occupancy in rats support its potential therapeutic utility in the treatment of depression. It does not affect the locomotor activity at doses several folds higher than its efficacy dose. It is devoid of cardiovascular and gastrointestinal side effects. Successful long-term safety studies in animals and phase-1 evaluation in healthy humans for safety, tolerability, and pharmacokinetics paved the way for its further development.
Nirogi, Ramakrishna,Mohammed, Abdul Rasheed,Shinde, Anil K.,Ravella, Srinivasa Rao,Bogaraju, Narsimha,Subramanian, Ramkumar,Mekala, Venkat Reddy,Palacharla, Raghava Choudary,Muddana, Nageswararao,Thentu, Jagadeesh Babu,Bhyrapuneni, Gopinadh,Abraham, Renny,Jasti, Venkat
p. 2833 - 2853
(2020/03/05)

Synthesis and bioactivities evaluation of L-pyroglutamic acid analogues from natural product lead
A series of L-pyroglutamic acid analogues from natural product lead were designed and synthesized, as well as their antifungal activities against Phytophthora infestans, neuritogenic activities, antibacterial activities and anti-inflammatory activities are described. The bioassays and SAR study showed that the majority of L-pyroglutamic acid esters have a significant antifungal activity against P. infestans, especially 2d and 2j demonstrated the best activities with EC50 values of 1.44 and 1.21 μg mL?1, which were about seven times that of commercial azoxystrobin (7.85 μg mL?1). Moreover, compounds 2e, 2g and 4d displayed anti-inflammatory activity against LPS-induced NO production in BV-2 microglial cells; neuritogenic activity in NGF-induced PC-12 cells is the same activity. This study demonstrates that compounds 2d and 2j are potential drugs to control P. infestans.
Gang, Fang-li,Zhu, Feng,Li, Xiao-ting,Wei, Jie-lu,Wu, Wen-jun,Zhang, Ji-wen
p. 4644 - 4649
(2018/08/21)

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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Paragraph 0033-0034

(2017/11/16)

POLYMYXIN ANALOGS USEFUL AS ANTIBIOTIC POTENTIATORS
The disclosure provides compounds of the formula (I) or a tautomer thereof, or a pharmaceutically acceptable salt of either of the foregoing. The variables A, R1, and R2 are defined in the disclosure. The disclosure further includes pharmaceutical compositions comprising a compound of formula I together with at least one pharmaceutically acceptable carrier. The disclosure also includes a method of sensitizing bacteria to an antibacterial agent, comprising administering to a patient infected with the bacteria, simultaneously or sequentially, a therapeutically effective amount of the antibacterial agent and a compound of formula (I).
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Paragraph 0170

(2017/12/09)

Diastereoselective synthesis and biological evaluation of enantiomerically pure tricyclic indolines
Tricyclic indolines are common in both natural products and synthetic chemical probes. In this study we demonstrated that enantiomerically pure tricyclic indolines can be prepared from an inexpensive commercially available chiral starting material, pyroglutamic acid. The synthesis features a highly diastereoselective gold-catalyzed cyclization of alkyne-tethered indoles and subsequent diastereoselective reductive ring-opening reaction. Using this approach, we synthesized analogs of our previously discovered tricyclic indoline probes that possess antibacterial and resistance-modifying activity. The biological activity against methicillin-resistant Staphylococcus aureus (MRSA) of these analogues was evaluated and reported. The synthetic approach reported may be leveraged in the future to prepare diastereopure chemical probes for the determination of biological targets for drug discovery.
He,Griffiths,Wang,Wang
supporting information
p. 4241 - 4245
(2017/07/10)

PROCESS FOR PREPARING DIPEPTIDYL PEPTIDASE IV INHIBITORS AND INTERMEDIATES THEREFOR
A process for preparing an amine of the structure which comprises a. treating an aqueous solution of a keto acid of the structure with ammonium formate, nicotinamide adenine dinucleotide, dithiothreitol and partially purified phenylalanine dehydrogenase and/or formate dehydrogenase enzyme (PDH/FDH); and b. adjusting pH of the reaction mixture with sodium hydroxide to form the desired amine which is substantially free of undesirable excess ammonium ions.
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Paragraph 0041; 0042; 0110

(2016/07/27)

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)

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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Page/Page column 170

(2015/12/17)

SPIRO COMPOUNDS AS HEPATITIS C VIRUS INHIBITORS
Disclosed are spiro compounds of formula (I), or stereomers, geometric isomers, tautomers, nitrogen oxides, hydrates, solvates, metabolites, pharmaceutically acceptable salts or prodrugs thereof. The compounds can be used to treat hepatitis C virus (HCV) infection or hepatitis C disease. Furthermore disclosed are pharmaceutical compositions containing the compounds and the method of using the compounds or pharmaceutical compositions in the treatment of HCV infection or hepatitis C disease.
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Paragraph 0449

(2015/11/09)

Stereoselective construction of a key hydroindole precursor of epidithiodiketopiperazine (ETP) natural products
An asymmetric synthetic strategy for constructing the divergent-synthesis monomer of epidithiodiketopiperazine (ETP) natural products has been successfully developed. The functionalized 2,3,3a,4,7,7a-hexahydroindole scaffold was constructed by a diastereoselective inverse electron-demand Diels-Alder (IEDDA) reaction. This journal is the Partner Organisations 2014.
Feng, Minghao,Jiang, Xuefeng
supporting information
p. 9690 - 9692
(2014/08/18)

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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Page/Page column 26-27

(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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Page/Page column 20

(2011/02/26)

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
scheme or table
p. 2772 - 2776
(2011/06/23)

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)

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)

Chemical reactivity of 6-diazo-5-oxo-l-norleucine (DON) catalyzed by metalloporphyrins (Fe,Ru)
The transfer of the metallocarbene derived from N- and O-protected 6-diazo-5-oxo-l-norleucine (DON) catalyzed by metalloporphyrins undergoes dimerization, cyclopropanation, N-H and S-H insertion reactions, respectively. An efficient and direct synthesis of 5-oxo-l-pipecolic acid from DON is described from unprotected 6-diazo-5-oxo-l-norleucine.
Le Maux, Paul,Nicolas, Irène,Chevance, Soizic,Simonneaux, Gérard
experimental part
p. 4462 - 4468
(2010/07/06)

Practical synthesis of the C-1027 aminosugar moiety
A concise and reliable synthetic route to the aminosugar moiety of the C-1027 chromophore was developed. The aminosugar moiety was synthesized from l-glutamic acid in 11 steps and 13% overall yield.
Hirai, Keiichiro,Tamura, Yukio,Sato, Itaru,Hirama, Masahiro
supporting information; scheme or table
p. 2156 - 2158
(2010/11/02)

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)

A practical ruthenium-catalyzed cleavage of the allyl protecting group in amides, lactams, imides, and congeners
A convenient methodology for the deprotection of N-allylic amide-like moieties was developed. The first examples accounting for the ruthenium-catalyzed deallylation of amides, lactams, imides, pyrazolidones, hydantoins, and oxazolidinones have been achieved by the sequential use of Grubbs carbene (isomerization step) and RuCl3 (oxidation step). A variety of substrates, including enantiopure multifunctional β- and γ-lactams, can be employed.
Alcaide, Benito,Almendros, Pedro,Alonso, Jose M.
p. 2874 - 2879
(2008/02/03)

Trans-2,5-Disubstituted pyrrolidines: Rapid stereocontrolled access from sulfones
A direct method for the reliable synthesis of trans-2,5-distributed pyrrolidines from pyroglutamic acid that was conducted at scale and without chromatographic purification of key intermediates was investigated. An analogous reaction involving the partial reduction of succinimides and displacement of the resulting lactol with benzenesulfinic acid yields sulfonyl pyrrolidinones. It was found that a highly diastereoselective and general approach to 2,5-difunctionalized pyrrolidines could be achieved by applying this strategy to the pyroglutamate system. The four step synthesis required no chromatographic purification of intermediates, where the product sulfone was readily purified by recrystallization and the sequence proceeded in 52% overall yield. The results show that such an approach would be of great importance for the preparation of substituted pyrrolidines in natural product systems.
Moloney, Mark G.,Panchal, Terry,Pike, Richard
p. 3894 - 3897
(2008/09/18)

Synthesis of macrocyclic analogues of the neuroprotective agent glycyl-l-prolyl-l-glutamic acid (GPE)
The syntheses of seven macrocyclic analogues of the neuroprotective tripeptide glycyl-l-prolyl-l-glutamic acid (GPE) 1 are described. Macrocycles 6 and 7 mimic the cis conformer of GPE whereas macrocycles 2-5, 8, and 9 mimic the trans conformer of GPE. The macrocyclic peptides of well-defined geometry were prepared via Grubbs ring closing metathesis of an appropriate diene precursor. In turn each of the diene precursors were prepared from the readily available allyl-substituted amino acid building blocks 12, 13, 14, 27, 36 and 51. The Royal Society of Chemistry 2006.
Harris, Paul W. R.,Brimble, Margaret A.
p. 2696 - 2709
(2008/02/08)

An improved synthesis of (-)-martinellic acid via radical addition-cyclization-elimination reaction of chiral oxime ether
A concise formal synthesis of (-)-martinellic acid has been accomplished by preparing optically active dipyrroloquinoline as a key synthetic intermediate, which was prepared via the radical addition-cyclization-elimination of oxime ether carrying an unsaturated ester followed by two chemoselective reductions of the carbonyl groups. Georg Thieme Verlag Stuttgart.
Miyata, Okiko,Shirai, Atsushi,Yoshino, Shintaro,Takeda, Yoshifumi,Sugiura, Makiko,Naito, Takeaki
p. 893 - 896
(2007/10/03)

A novel azetidinyl γ-lactam based peptide with a preference for β-turn conformation
Synthesis of a new azetidinyl γ-lactam based peptides 1-3 with the preference for β-turn conformation is discussed. The tripeptide model compounds, namely the trans and the corresponding cis isomers, were studied by H NMR spectroscopy to measure the temperature coefficients of the two NH photons. It was observed that temperature coefficient NH of glycine was lowest, phenyl alanine-NH has higher temperature coefficient, and for both the cis tripeptides the temperature coefficients of shifts for all the NHs are above 5.0. The results show that the stereochemistry of β-lactam ring plays a key role in controlling the conformation of the peptides.
Basak, Amit,Ghosh, Subhash C.,Das, Amit K.,Bertolasi, Valerio
p. 4050 - 4052
(2007/10/03)

Studies towards the total synthesis of batzelladine A
Application of a diastereoselective three-component coupling to the bicyclic core of the batzelladine alkaloids is described. The synthesis features the elaboration of glutamic acid by use of Eschenmoser sulfide contraction. An earlier approach is also included, which shows some limitations of dithiane chemistry when applied to the particular compounds required for this target.
Elliott, Mark C.,Long, Matthew S.
p. 2003 - 2011
(2007/10/03)

Novel ruthenium-catalyzed cleavage of allyl protecting group in lactams
A convenient and general method of synthesis of NH-lactams via Grubbs' carbene promoted isomerization of the respective N-allyl lactams followed by RuCl3-catalyzed enamide cleavage has been developed.
Alcaide, Benito,Almendros, Pedro,Alonso, José M.
p. 8693 - 8695
(2007/10/03)

A concise synthesis of (2S,4R)- and (2S,4S)-4-methylglutamic acid
A concise, multi-gram scale method for producing the bioactive and enantiomerically pure epimers, (2S,4R)- and (2S,4S)-glutamic acids, in a single synthetic scheme is described.
Gu, Zi-Qiang,Li, Min
p. 3203 - 3205
(2007/10/03)

Five- and six-membered ring opening of pyroglutamic diketopiperazine
A variety of ring-opening reactions of pyroglutamic diketopiperazine at both the five-membered and six-membered rings is described. Mild, basic conditions facilitate nucleophilic attack by amines at the diketopiperazine carbonyls giving pyroglutamides in excellent yield. Reaction with nucleophiles under acidic conditions give bis-glutamate derivatives of 2,5-diketopiperazine (DKP). These reactions provide simple, two-step sequences to pyroglutamides and symmetrical diketopiperazines from commercial pyroglutamic acid with control of product dictated by reaction conditions, catalyst, and nucleophile.
Parrish, Dennis A.,Mathias, Lon J.
p. 1820 - 1826
(2007/10/03)

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)

C-glycosylation of cyclic N-acyliminium ions with trimethylsilyloxyfuran
C-glycosylation of 2-methoxy-5-alkoxycarbonyl pyrrolidines with trimethylsilyloxyfuran allows us to obtain the corresponding pyrrolidines contigus to a α,β-unsaturated butyrolactone.
Pichon, Marianne,Figadere, Bruno,Cave, Andre
p. 7963 - 7966
(2007/10/03)

Functionalised pyrrolidinones derived from (S)-pyroglutamic acid
The generation of the lactam enolate derived from bicyclic lactams 2a-c, prepared from (S)-pyroglutamic acid 1a, and subsequent reaction with a range of electrophiles, is reported. Exo-diastereoselectivity is generally favoured. The deprotection of some of these adducts to give functionalised hydroxymethylpyrrolidinones is readily achieved by simple hemiaminal ether cleavage under acidic conditions.
Beard, Mark J.,Bailey, Jonathan H.,Cherry, David T.,Moloney, Mark G.,Shim, Sung Bo,Statham, Kathryn A.,Bamford, Mark J.,Lamont, R. Brian
p. 3719 - 3740
(2007/10/03)

SET-photosensitized reactions of α-silylamino-enones and ynones proceeding by 6-endo α-amino radical cyclization pathways
SET-photosensitized reactions of α,β-enones and -ynones containing tethered α-silylamine functions are described. The processes lead to hydropyridine ring construction via pathways involving 6-endo type α-amino radical cyclizations. High degrees of regio- and stereocontrol attend these reactions.
Khim, Seock-Kyu,Cederstrom, Ericka,Ferri, Dino C.,Mariano, Patrick S.
p. 3195 - 3222
(2007/10/03)

Cosmetic composition
A composition suitable for topical application to mammalian skin and hair for inducing, maintaining or increasing hair growth comprises a hair growth promoter chosen from glutamine derivatives and salts thereof. The composition preferably also comprises an activity enhancer which may be chosen from hair growth stimulants, penetration enhancers and cationic polymers.
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(2008/06/13)

Studies on pyrrolidones. An improved synthesis of pyroglutamoyl chloride
The reaction of trimethylsilyl pyroglutamate with oxalyl chloride at room temperature easily yields pyroglutamoyl chloride. This unstable compound, obtained with difficulty by other methods, is suitable for the preparation of pyroglutamic esters and amides.
Rigo,El Ghammarti,Gautret,Couturier
p. 2597 - 2607
(2007/10/02)

Asymmetric Radical Cyclization With Pyroglutamate: Synthesis of 7-Substituted Pyrrolizidinones
Chiral, non-racemic N-(2-iodoethyl)-5-vinylpyrrolidin-2-ones have been synthesized and then cyclized with tributyltin hydride and azoisobutyronitrile (AIBN) to produce chiral, non-racemic pyrrolizidin-2-ones, with high diastereoselectivity.Reduction of the lactam moiety provides a facile route to naturally occuring pyrrolizidine alkaloids.
Keusenkothen, Paul F.,Smith, Michael B.
p. 2485 - 2492
(2007/10/02)

5(R)-Methyl-1-(chloromethyl)-2-pyrrolidinone: A New Reagent for the Determination of Enantiomeric Composition of Alcohols
We have prepared a new chiral nonracemic reagent (5(R)-methyl-1-(chloromethyl)-2-pyrrolidinone) in enantiopure form that reacts with alcohols containing a stereogenic center to produce diastereomeric N-(alkoxymethyl)-2-pyrrolidinone derivatives.These derivatives exhibit large and easily observed diastereotopic signals in the proton NMR that allow direct determination of diastereomeric ratio (percent dr) for the product.
Smith, Michael B.,Dembofsky, Bruce T.,Son, Young Chan
p. 1719 - 1725
(2007/10/02)

Cosmetic composition containing DOPA derivatives
A composition for topical application to human hair or skin contains a chemical analogue of dihydroxyphenyl alanine (DOPA). This chemical analogue can be absorbed by skin or by a hair follicle and metabolised in-vivo, thus leading to the formation of melanin in skin or to the growth of melanin-pigmented hair. Consequently the composition can give controlled skin darkening to mimic sun-induced tanning or can bring about the growth of dar hair in place of the grey or white hair.
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(2008/06/13)

Cosmestic composition
A composition suitable for topical application to mammalian skin and hair for inducing, maintaining or increasing hair growth comprises a hair growth promoter chosen from glutamic acid derivatives and salts thereof. The composition preferably also comprises an activity enhancer which may be chosen from hair growth stimulants, penetration enhancers and cationic polymers.
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(2008/06/13)

Asymmetric radical cyclizations: The synthesis of 6-alkyl pyrrolizidin-2-ones
This work describes the use of ethyl (5S)-carboethoxy-2-pyrrolidinone (ethyl pyroglutamate) as a chiral starting material for use in radical cyclization reactions. Pyroglutamate is converted to a 5-iodomethyl-N-allylic-2-pyrrolidinone that undergoes radical cyclization under mild conditions. The products are 6-substituted pyrrolizidinone derivatives, produced with high diastereoselectivity.
Keusenkothen,Smith
p. 2977 - 2992
(2007/10/02)

Asymmetric synthesis of (S)-4-aminohex-5-enoic acid: A potent inhibitor of 4-aminobutyrate-2-oxoglutarate aminotransferase
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Kwon,Keusenkothen,Smith
p. 6169 - 6173
(2007/10/02)

Cosmetic composition
A composition suitable for topical application to mammalian skin or hair for inducing, maintaining or increasing hair growth comprises: (i) a first chemical inhibitor chosen from proteoglycanase inhibitors, glycosaminoglycanase inhibitors, glycosaminoglycan chain cellular uptake inhibitors or mixtures thereof; and (ii) a cosmetically acceptable vehicle for the chemical inhibitor; provided that when the first chemical inhibitor is a weak inhibitor, such that a 1 mM aqueous solution of the inhibitor reduces proteoglycanase activity, glycosaminoglycanase activity or cellular uptake of glycosaminoglycan chains, by from 5 to 50%, in accordance with at least one of the assay tests as herein described, then there is also present in the composition a second chemical inhibitor and/or an activity enhancer. When minoxidil is the sole chemical inhibitor, then the activity enhancer is a penetration enhancer chosen from a limited number of materials, including certain esters and cationic polymers. The total amount of chemical inhibitor present in the composition is sufficient to increase hair growth in the rat, when said composition is applied topically thereto, by at least 10% more than that obtainable using a control composition from which the said inhibitors have been omitted.
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(2008/06/13)

Amino Acid Synthesis Using (L)-Pyroglutamic Acid as a Chiral Starting Material
Deprotonation of protected pyroglutamates 1(c), 1(d), and 1(e) with lithium di-isopropylamine (LDA) or lithium hexamethyldisilazide (LiHDMS) in THF, followed by reaction with electrophiles, leads to the formation of 4-substituted pyroglutamates in good yield.This approach has been used for the synthesis of the novel amino acid (4).Key Words: pyroglutamic acid; chiral amino acid synthesis
Baldwin, Jack E.,Miranda, Tania,Moloney, Mark,Hokelek, Tuncer
p. 7459 - 7468
(2007/10/02)

PREPARATION OF OPTICALLY PURE ω-HYDROXYMETHYL LACTAMS
Thermal cyclization of L-glutamate and L-α-aminoadipate to the corresponding lactam esters can be achieved without racemization.LiBH4 reduction of the esters provides optically pure hydroxymethyl lactams.
Huang, Sung-Ben,Nelson, Jeffrey S.,Weller, Dwight D.
p. 3485 - 3496
(2007/10/02)

Amino Acids. 7. A Novel Synthetic Route to L-Proline
Reaction of L-5-oxoproline esters L-2 with phosgene at 0 deg C gives L-5,5-dichloro-1-(chlorocarbonyl)proline esters L-6, which readily lose hydrogen chloride to form L-5-chloro-1-(chlorocarbonyl)-4,5-dehydroproline esters L-7.Catalytic hydrogenation (Pd/C, 180 bar) of L-7 yields L-1-(chlorocarbonyl)proline esters L-15 and thence, upon hydrolysis, L-proline (L-17).A 'one-pot reaction' for the whole sequence is described, starting from easily accessible L-5-oxoproline esters and yielding L-proline in 78percent overall yield and 99.7percent optical purity.
Drauz, Karlheinz,Kleemann, Axel,Martens, Juergen,Scherberich, Paul,Effenberger, Franz
p. 3494 - 3498
(2007/10/02)

Process for preparing 5-vinyl-2-pyrrolidinone and intermediates therefor
4-Amino-5-hexenoic acid is prepared by: (a) reacting 5-oxo-2-pyrrolidine-acetonitrile with hydrogen and dimethylamine in the presence of a palladium catalyst to form N,N-dimethyl-2-[5'-oxo-2'-pyrrolidine]ethylamine; (b) oxidizing N,N-dimethyl-2-[5'-oxo-2'-pyrrolidine]-ethylamine to produce the corresponding N-oxide derivative; (c) pyrolysis of the N-oxide derivative to form 5-vinyl-2-pyrrolidinone; (d) optionally, separating N,N-dimethyl-2-[5'-oxo-2'-pyrrolidine]ethylamine by-product from the 5-vinyl-2-pyrrolidinone product; and (e) hydrolyzing 5-vinyl-2-pyrrolidinone to form 4-amino-5-hexenoic acid.
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(2008/06/13)

Intramolecular Aminolysis of Esters. O-Acetylserine and γ-Esters of Glutamic Acid
The kinetics of the concurrent hydrolysis and intramolecular aminolysis of γ-ethyl glutamate have been studied in aqueous solution (40 deg C) in range of pH 7.6-10.4.While hydrolysis contributes only 3percent to the overall rate of reaction of γ-ethyl glutamate at pH 10.4, its importance relative to aminolysis increases with decreasing pH; at pH 8, the hydrolysis pathway accounts for 32percent of the rate of disapperance of the ester.The pH-rate profile for the aminolysis pathway indicates the presence of water and a hydroxide-catalyzed reaction and provides no evidence for intermediates.The conversion of diethyl glutamate to pyrrolidone-5-carboxylate may occur through either of two competing pathways: (a) rate-determining aminolysis to ethyl pyrrolidone-5-carboxylate, followed by rapid hydrolysis of the ester; (b) rate-determining hydrolysis to γ-ethylglutamate, followed by rapid cyclization.The pH-rate profile for the intramolecular aminolysis of O-acetylserine, determined at zero buffer concentration (30 deg C), has the complex appearance characteristic for acyl-transfer reactions involving neutral and anionic tetrahedral intermediates.Quantitative support for the interpretation of the pH-rate profile comes from the analysis of the nonlinear increases in the rate of aminolysis observed in the presence of increasing concentrations of phosphate buffers.The results of this and earlier studies suggest that there may not be major differences in the mechanisms of the intra- and intermolecular aminolysis of weakly acidic alcohols.
Caswell, Michael,Chaturvedi, Rama K.,Lane, Stuart M.,Zvilichovsky, Bina,Schmir, Gaston L.
p. 1585 - 1593
(2007/10/02)