- Pharmacodynamic and pharmacokinetic profiles of a neurotensin receptor type 2 (NTS2) analgesic macrocyclic analog
-
The current opioid crisis highlights the urgent need to develop safe and effective pain medications. Thus, neurotensin (NT) compounds represent a promising approach, as the antinociceptive effects of NT are mediated by activation of the two G protein-coupled receptor subtypes (i.e., NTS1 and NTS2) and produce potent opioid-independent analgesia. Here, we describe the synthesis and pharmacodynamic and pharmacokinetic properties of the first constrained NTS2 macrocyclic NT(8–13) analog. The Tyr11 residue of NT(8–13) was replaced with a Trp residue to achieve NTS2 selectivity, and a rationally designed side-chain to side-chain macrocyclization reaction was applied between Lys8 and Trp11 to constrain the peptide in an active binding conformation and limit its recognition by proteolytic enzymes. The resulting macrocyclic peptide, CR-01-64, exhibited high-affinity for NTS2 (Ki 7.0 nM), with a more than 125-fold selectivity over NTS1, as well as an improved plasma stability profile (t1/2 > 24 h) compared with NT (t1/2 ~ 2 min). Following intrathecal administration, CR-01-64 exerted dose-dependent and long-lasting analgesic effects in acute (ED50 = 4.6 μg/kg) and tonic (ED50 = 7.1 μg/kg) pain models as well as strong mechanical anti-allodynic effects in the CFA-induced chronic inflammatory pain model. Of particular importance, this constrained NTS2 analog exerted potent nonopioid antinociceptive effects and potentiated opioid-induced analgesia when combined with morphine. At high doses, CR-01-64 did not cause hypothermia or ileum relaxation, although it did induce mild and short-term hypotension, all of which are physiological effects associated with NTS1 activation. Overall, these results demonstrate the strong therapeutic potential of NTS2-selective analogs for the management of pain.
- Chartier, Magali,Desgagné, Michael,Sousbie, Marc,Rumsby, Charles,Chevillard, Lucie,Théroux, Léa,Haroune, Lounès,C?té, Jér?me,Longpré, Jean-Michel,Boudreault, Pierre-Luc,Marsault, éric,Sarret, Philippe
-
-
- Synthesis of 2-D-L-tryptophan by sequential Ir-catalyzed reactions
-
Herein, we report a practical synthesis of 2-D-l-tryptophan via sequential Ir-catalyzed C–H borylation, and Ir-catalyzed C-2-deborylative deuteration steps. In this synthetic sequence, deprotection of the Boc and methyl ester groups proved challenging, due to replacement of deuterium with hydrogen. However, mild deprotection conditions were developed to avoid this D/H scrambling. Further, 2-D-L-Tryptophan is stable in many buffers used for biological studies.
- Vallakati, Ravikrishna,Plotnikov, Abel T.,Altman, Ryan A.
-
p. 2261 - 2264
(2019/03/04)
-
- Asymmetric and Geometry-Selective α-Alkenylation of α-Amino Acids
-
Both E- and Z-N′-alkenyl urea derivatives of imidazolidinones may be formed selectively from enantiopure α-amino acids. Generation of their enolate derivatives in the presence of K+ and [18]crown-6 induces intramolecular migration of the alkeny
- Abas, Hossay,Mas-Roselló, Josep,Amer, Mostafa Mahmoud,Durand, Derek J.,Groleau, Robin R.,Fey, Natalie,Clayden, Jonathan
-
supporting information
p. 2418 - 2422
(2019/02/09)
-
- Unlocking the potential of phenacyl protecting groups: CO2-based formation and photocatalytic release of caged amines
-
Orthogonal protection and deprotection of amines remain important tools in synthetic design as well as in chemical biology and material research applications. A robust, highly efficient, and sustainable method for the formation of phenacyl-based carbamate esters was developed using CO2 for the in situ preparation of the intermediate carbamates. Our mild and broadly applicable protocol allows for the formation of phenacyl urethanes of anilines, primary amines, including amino acids, and secondary amines in high to excellent yields. Moreover, we demonstrate the utility by a mild and convenient photocatalytic deprotection protocol using visible light. A key feature of the [Ru(bpy)3](PF6)2-catalyzed method is the use of ascorbic acid as reductive quencher in a neutral, buffered, two-phase acetonitrile/water mixture, granting fast and highly selective deprotection for all presented examples.
- Speckmeier, Elisabeth,Klimkait, Michael,Zeitler, Kirsten
-
p. 3738 - 3745
(2018/04/14)
-
- Synthesis, biological evaluation, and molecular modeling studies of chiral chloroquine analogues as antimalarial agents
-
In a focused exploration, we designed, synthesized, and biologically evaluated chiral conjugated new chloroquine (CQ) analogues with substituted piperazines as antimalarial agents. In vitro as well as in vivo studies revealed that compound 7c showed potent activity (in vitro 50% inhibitory concentration, 56.98 nM for strain 3D7 and 97.76 nM for strain K1; selectivity index in vivo [up to at a dose of 12.5 mg/kg of body weight], 3,510) as a new lead antimalarial agent. Other compounds (compounds 6b, 6d, 7d, 7h, 8c, 8d, 9a, and 9c) also showed moderate activity against a CQ-sensitive strain (3D7) and superior activity against a CQ-resistant strain (K1) of Plasmodium falciparum. Furthermore, we carried out docking and three-dimensional quantitative structure-activity relationship (3D-QSAR) studies of all in-house data sets (168 molecules) of chiral CQ analogues to explain the structure-activity relationships (SAR). Our new findings specify the significance of the H-bond interaction with the side chain of heme for biological activity. In addition, the 3D-QSAR study against the 3D7 strain indicated the favorable and unfavorable sites of CQ analogues for incorporating steric, hydrophobic, and electropositive groups to improve the antimalarial activity.
- Kondaparla, Srinivasarao,Debnath, Utsab,Dola, Vasantha Rao,Sinha, Manish,Katti, Seturam B.,Soni, Awakash,Srivastava, Kumkum,Puri, Sunil K.
-
-
- Selective Reductive Elimination at Alkyl Palladium(IV) by Dissociative Ligand Ionization: Catalytic C(sp3)?H Amination to Azetidines
-
A palladium(II)-catalyzed γ-C?H amination of cyclic alkyl amines to deliver highly substituted azetidines is reported. The use of a benziodoxole tosylate oxidant in combination with AgOAc was found to be crucial for controlling a selective reductive elimination pathway to the azetidines. The process is tolerant of a range of functional groups, including structural features derived from chiral α-amino alcohols, and leads to the diastereoselective formation of enantiopure azetidines.
- Nappi, Manuel,He, Chuan,Whitehurst, William G.,Chappell, Ben G. N.,Gaunt, Matthew J.
-
supporting information
p. 3178 - 3182
(2018/02/28)
-
- An environmentally friendly protocol for oxidative halocyclization of tryptamine and tryptophol derivatives
-
An environmentally friendly and efficient protocol (KX/oxone) for oxidative halocyclization of tryptamine/tryptophol derivatives was developed and demonstrated with 28 examples and concise total synthesis of cyclotryptamine alkaloid protubonines A and B. The distinct advantage of this protocol over all previous methods is that no organic byproduct is generated from a halogenating agent or oxidant, thus greatly reducing the environmental impact of halocyclization and facilitating the post-reaction purification.
- Xu, Jun,Tong, Rongbiao
-
supporting information
p. 2952 - 2956
(2017/07/24)
-
- Design, synthesis, and evaluation of novel Akt1 inhibitors based on an indole scaffold
-
A new series of potential Akt1 inhibitors with indole scaffold were designed and synthesized. The antiproliferative activity against PC-3 cell line and enzyme inhibitory activity against Akt1 were evaluated. Among them, some compounds showed much more potent antiproliferative activity and stronger Akt1 inhibitory activity compared to the positive control of GSK690693. In particular, compound 19b exhibited the most potent inhibitory activity against Akt1 with inhibition rate of 70.3% at a concentration of 10?nm. Furthermore, compound 19b could dose dependently reduce the phosphorylation of the downstream GSK3β protein in the PC-3 cell line and displayed fivefold higher antiproliferative activity against PC-3 cell line with IC50 value of 3.1?±?0.1?μm than positive control (15.5?±?0.4?μm). Herein, compound 19b may serve as a promising lead for further optimization and development of novel Akt1 inhibitors based on an indole scaffold.
- Yang, Dezhi,Tong, Dongdong,Zhang, Qian,Wang, Yongtao,Sun, Jing,Zhang, Fenghe,Zhao, Guisen
-
p. 791 - 803
(2017/09/30)
-
- Cyclotryptophan Mycotoxins: Short Synthesis of the Desymmetrized meso -Chimonantine Core of Leptosin C
-
The desymmetrized meso-chimonantine core of leptosin C was prepared in a short stereoselective convergent sequence in 5 steps as the longest linear path from methyl l-tryptophan hydrochloride as starting material. The key step of this approach was a diastereoselective [4+2] cycloaddition between the bromooxindole and tryptophan derivatives allowing to define the adjacent quaternary benzylic centers in a high chemical yield.
- Olaizola, Iurre,Abdine, Racha Abed Ali,Dhimane, Hamid,Dalko, Peter I.
-
p. 391 - 396
(2016/12/24)
-
- AgNTf2-mediated arylation of bromopyrroloindolines
-
The silver(I)-mediated arylation of bromopyrroloindolines was developed. The selection of silver salts was crucial to obtain arylated compounds in high yields. Among the various tested silver(I) salts, AgNTf2 was the most effective agent for ar
- Sato, Soichiro,Hirayama, Azusa,Adachi, Tohma,Kawauchi, Daichi,Ueda, Hirofumi,Tokuyama, Hidetoshi
-
p. 1940 - 1957
(2017/10/24)
-
- A Mild and General Larock Indolization Protocol for the Preparation of Unnatural Tryptophans
-
A mild and general protocol for the Pd(0)-catalyzed heteroannulation of o-bromoanilines and alkynes is described. Application of a Pd(0)/P(tBu)3 catalyst system enables the efficient coupling of o-bromoanilines at 60 °C, mitigating deleterious side reactions and enabling access to a broad range of useful unnatural tryptophans. The utility of this new protocol is demonstrated in the highly convergent total synthesis of the bisindole natural product (-)-aspergilazine A.
- Chuang, Kangway V.,Kieffer, Madeleine E.,Reisman, Sarah E.
-
supporting information
p. 4750 - 4753
(2016/09/28)
-
- Unified mild reaction conditions for C2-selective Pd-catalysed tryptophan arylation, including tryptophan-containing peptides
-
Pd-mediated C-H bond functionalisation protocols have been designed and developed on tryptophan derivatives and tryptophan-containing peptides. The examination of different arylation reactions (three sets of different conditions A-C), all of which are notable for their low temperatures (≤40°C), allowed identification of unified and complementary synthetic approaches toward a series of functionalised tryptophan-containing products. Tryptophan-containing peptides demonstrated to be susceptible to aromatic oxidation were successfully and selectively modified through the application of diaryliodonium salts in good yields.
- Reay, Alan J.,Williams, Thomas J.,Fairlamb, Ian J. S.
-
p. 8298 - 8309
(2015/08/03)
-
- Total synthesis and structural revision of (-)-protubonine A and (-)-protubonine B
-
The proposed structures of (-)-protubonine A and (-)-protubonine B, which are pyrrolidinoindoline diketopiperazine alkaloids that were isolated from the marine-derived fungus Aspergillus sp. SF-5044, have been synthesized and correspond to diastereomers of the natural isolates. The total syntheses, herein, established the stereostructures of the alkaloids as the C-11 epimers of the purported structures. The natural products (-)-protubonine A and (-)-protubonine B have the absolute configuration of (2R,3R,11S,15S), and this has been confirmed by total synthesis. Copyright
- Lorenzo, Paula,Alvarez, Rosana,De Lera, Angel R.
-
p. 2557 - 2564
(2014/05/06)
-
- Design, synthesis and evaluation of novel indole derivatives as AKT inhibitors
-
Herein, we describe the discovery and synthesis of a new series of 1,2,4,7-tetra-substituted indole derivatives as novel AKT inhibitors by optimization of a weak hit methyl 4-(2-aminoethoxy)-1H-indole-2-carboxylate (1). Both representative compounds 6a and 6o exhibited the most potent inhibitory activities against AKT1, with inhibition rates of 72.5% and 78.6%, respectively, at concentrations of 10 nM. In addition, compounds 6a and 6o also potently inhibited the phosphorylation of the downstream GSK3 protein and displayed slightly better anti-proliferative activities in a prostate cancer cell line.
- Yang, Dezhi,Wang, Peng,Liu, Jianzhen,Xing, Hualu,Liu, Yang,Xie, Wencheng,Zhao, Guisen
-
p. 366 - 373
(2014/01/17)
-
- Straightforward access to hexahydropyrrolo[2,3-b]indole core by a regioselective c3-azo coupling reaction of arenediazonium compounds with tryptamines
-
A base-mediated regioselective electrophilic addition of arenediazonium salts at the C3-position of tryptamines followed by cyclization provides an efficient entry to C3-nitrogenated hexahydropyrrolo[2,3-b]indoles (HPIs) that can subsequently be transformed into 3-arylhexahydropyrrolo[2,3-b]indoles and other HPI derivatives. The reaction is the first example of a 1,2-diamination that utilizes easily accessible arenediazonium salts as nitrogenous electrophiles. Copyright
- Stephens, David E.,Larionov, Oleg V.
-
supporting information
p. 3662 - 3670
(2014/06/23)
-
- Discovery of the first N -hydroxycinnamamide-based histone deacetylase 1/3 dual inhibitors with potent oral antitumor activity
-
In our previous study, we designed and synthesized a novel series of N-hydroxycinnamamide-based HDAC inhibitors (HDACIs), among which the representative compound 14a exhibited promising HDACs inhibition and antitumor activity. In this current study, we report the development of a more potent class of N-hydroxycinnamamide-based HDACIs, using 14a as lead, among which, compound 11r gave IC50 values of 11.8, 498.1, 3.9, 2000.8, 5700.4, 308.2, and 900.4 nM for the inhibition of HDAC1, HDAC2, HDAC3, HDAC8, HDAC4, HDAC6, and HDAC11, exhibiting dual HDAC1/3 selectivity. Compounds 11e, 11r, 11w, and 11y showed excellent growth inhibition in multiple tumor cell lines. In vivo antitumor assay in U937 xenograft model identified compound 11r as a potent, orally active HDACI. To the best of our knowledge, this work constitutes the first report of oral active N-hydroxycinnamamide-based HDACIs with dual HDAC1/3 selectivity.
- Li, Xiaoyang,Inks, Elizabeth S.,Li, Xiaoguang,Hou, Jinning,Chou, C. James,Zhang, Jian,Jiang, Yuqi,Zhang, Yingjie,Xu, Wenfang
-
p. 3324 - 3341
(2014/05/20)
-
- Synthesis of tryptophans by Lewis acid promoted ring-opening of aziridine-2-carboxylates: Optimization of protecting group and Lewis acid
-
The preparation of tryptophan derivatives through the Lewis acid promoted substitution of aziridine carboxylates with indole was found to be accompanied by a ring-expansion reaction to generate an oxazolidinone byproduct. The ratio of tryptophan to oxazol
- Tirotta, Ilaria,Fifer, Nathan L.,Eakins, Julia,Hutton, Craig A.
-
p. 618 - 620
(2013/02/23)
-
- Development of N-hydroxycinnamamide-based histone deacetylase inhibitors with an indole-containing Cap group
-
A novel series of histone deacetylase inhibitors combining N-hydroxycinnamamide bioactive fragment and indole bioactive fragment was designed and synthesized. Several compounds (17c, 17g, 17h, 17j, and 17k) exhibited comparable, even superior, total HDACs inhibitory activity and in vitro antiproliferative activities relative to the approved drug SAHA. A representative compound 17a with moderate HDACs inhibition was progressed to isoform selectivity profile, Western blot analysis, and in vivo antitumor assay. Although HDACs isoform selectivity of 17a was similar to that of SAHA, our Western blot results indicated that intracellular effects of 17a at 1 μM were class I selective. It was noteworthy that the effect on histone H4 acetylation of SAHA decreased with time, while the effect on histone H4 acetylation of 17a was maintained and even increased. Most importantly, compound 17a exhibited promising in vivo antitumor activity in a U937 xenograft model.
- Zhang, Yingjie,Yang, Penghui,Chou, C. James,Liu, Chunxi,Wang, Xuejian,Xu, Wenfang
-
p. 235 - 238
(2013/03/28)
-
- A fluorous Mukaiyama coupling reagent for a concise condensation reaction: Utility of medium-fluorous strategy
-
The entire study of condensation reactions using various fluorous Mukaiyama reagents, including a novel medium-fluorous strategy, is described. A Mukaiyama reagent bearing a medium-fluorous content tag, between 40 and 60% fluorine by weight, was prepared and examined in ester and amide-forming condensation reactions. At the end of the reactions, the fluorous pyridone by-product was effectively separated from non-fluorous components by increasing the water content of the crude reaction mixture and subsequent filtration of the precipitate. It is also shown that Mukaiyama reagents bearing a fluorous tag increase the reaction rate considerably when compared to their non-fluorous tagged counterpart. Interestingly, it was observed that the longer the fluorous chain, the higher the activity of the Mukaiyama reagent.
- Sugiyama, Yuya,Kurata, Yuki,Kunda, Yoko,Miyazaki, Atsushi,Matsui, Junko,Nakamura, Shuichi,Hamamoto, Hiromi,Shioiri, Takayuki,Matsugi, Masato
-
experimental part
p. 3885 - 3892
(2012/07/02)
-
- Orthogonal protecting groups in the synthesis of tryptophanyl- hexahydropyrroloindoles
-
The synthesis of various polycyclic systems containing aC 3a-Ni bond between a hexahydropyrrolo[2,3-b]indole and an indole tryptophan is described here. A series of experiments were performed to determine the best combination of five orthogonal protecting groups and the best reaction conditions for formation of said bond, which is a common feature among many recently discovered marine natural products.
- Ruiz-Sanchis, Pau,Savina, Svetlana A.,Acosta, Gerardo A.,Albericio, Fernando,Alvarez, Mercedes
-
supporting information; experimental part
p. 67 - 73
(2012/01/15)
-
- Enantioselective fluorescent sensors for amino acid derivatives based on BINOL bearing S-tryptophan Unit: Synthesis and chiral recognition
-
Four novel derivatives of BINOL bearing Stryptophan unit have been prepared and the structures of these compounds characterized by IR, MS, 1H and 13C NMR spectroscopy and elemental analysis. The enantioselective recognition of these receptors has been studied by fluorescence titration and 1H NMR spectroscopy. The receptors exhibited different chiral recognition abilities towards N-Boc-protected amino acid anions and formed 1:1 complexes between host and guest. Receptors exhibit excellent enantioselective fluorescent recognition ability towards the amino acid derivatives. Springer Science+Business Media, LLC 2011.
- Xu, Kuo-Xi,Cheng, Peng-Fei,Zhao, Jin,Wang, Chao-Jie
-
scheme or table
p. 991 - 1000
(2012/04/10)
-
- The 2-(triphenylsilyl)ethoxycarbonyl-("Tpseoc"-) group: A new silicon-based, fluoride cleavable oxycarbonyl protecting group highly orthogonal to the Boc-, Fmoc- and Cbz-groups
-
Starting from 2-(triphenylsilyl)ethanol a new oxycarbonyl protecting group cleavable by fluoride ion induced Peterson-elimination has been developed. Known 2-(triphenylsilyl)ethanol has been prepared from commercially available triphenylvinylsilane by a hydroboration-oxidation sequence using the sterically hindered borane reagent 9-BBN. The silyl alcohol was subsequently transformed into its chloroformate, imidazolylcarboxylic acid ester and p-nitrophenyl carbonate and used in standard protocols for the formation of carbamates and carbonates. The Tpseoc group proved to be highly resistant against acidic conditions applied in removal of tert-butyl esters and the t-Boc-group. It also withstood catalytic hydrogenation, treatment with morpholine, methylhydrazine and Pd-reagents/allyl-scavanger combinations, conditions required to cleave Cbz-, Fmoc-, phthalimide- and Alloc-groups. The Tpseoc-group is cleaved upon treatment with TBAF/CsF at 0 °C or r.t. with cleavage times reaching from 10 min. to 24 h. Its orthogonality, ease of cleavage and UV-detectability makes the Tpseoc-group a promising alternative to other widely used silicon based amine protecting groups like the Teoc- and SES-groups.
- Golkowski, Martin,Ziegler, Thomas
-
experimental part
p. 4695 - 4718
(2011/08/10)
-
- An alternative and facile purification procedure of amidation and esterification reactions using a medium fluorous Mukaiyama reagent
-
A convenient methodology for the separation of a fluorous by-product using fluorous chemistry is described. A Mukaiyama coupling reagent bearing a medium fluorous tag, between 40% and 60% fluorine by weight, can be effectively separated from non-fluorous components by increasing the water content of the crude reaction mixture and subsequent filtration. Additional fluorous solid phase extraction is not necessary.
- Matsugi, Masato,Suganuma, Misaki,Yoshida, Shoko,Hasebe, Shohei,Kunda, Yoko,Hagihara, Kotaro,Oka, Sayaka
-
scheme or table
p. 6573 - 6574
(2009/04/05)
-
- Copper-catalyzed cyclization of lodo-tryptophans: A straightforward synthesis of pyrroloindoles
-
(Chemical Equation Presented) Pyrroloindoles are a key structural motif found in a wide number of biologically active alkaloids. Intramolecular copper-catalyzed coupling of readily accessible 2-iodo-tryptophan derivatives occurs in excellent yield, afford
- Coste, Alexis,Toumi, Mathieu,Wright, Karen,Razafimahaleo, Vanessa,Couty, Francois,Marrot, Jerome,Evano, Gwilherm
-
scheme or table
p. 3841 - 3844
(2009/07/01)
-
- Enantioselective fluorescent sensors for chiral carboxylates based on calix[4]arenes bearing an L-tryptophan unit
-
Two-armed chiral calix[4]arenes (3a-c) functionalized at the lower ring with L-tryptophan units have been prepared and the structures of these receptors characterized by IR, MS, 1H, and 13C NMR spectroscopy and elemental analysis. The enantioselective recognition of these receptors has been studied by fluorescence titration and 1H NMR spectroscopy. The receptors exhibited different chiral recognition abilities towards some enantiomers of chiral materials and formed 1:1 complexes between host and guest. Receptor 3a exhibits excellent enantioselective fluorescent recognition ability towards the N-Boc-protected alanine anion and 3b reveals good enantioselective recognition ability towards the enantiomers of mandelate. Wiley-VCH Verlag GmbH & Co. KGaA, 2007.
- Qing, Guang-Yan,He, Yong-Bing,Wang, Feng,Qin, Hai-Juan,Hu, Chen-Guang,Yang, Xi
-
p. 1768 - 1778
(2008/02/08)
-
- Palladium-catalyzed, modular synthesis of highly functionalized indoles and tryptophans by direct annulation of substituted o-haloanilines and aldehydes
-
(Chemical Equation Presented) One-pot synthesis of indoles by a palladium-catalyzed annulation of ortho-haloanilines and aldehydes has been developed. Coupling of ortho-iodoaniline with aldehyde is realized under mild ligandless conditions [Pd(OAc)2, DABCO, DMF, 85°C], whereas X-Phos is found to be the ligand of choice for coupling reactions involving ortho-chloroanilines/ortho-bromoanilines and aldehydes. A variety of orthohaloanilines with different electronic properties are suitable substrates, and aldehydes including chiral ones participated in this reaction without racemization. Coupling of (S)-2-N,N-di-tert-butoxycarbonyl-5-oxopentanoate, derived from L-glutamic acid, with ortho-haloanilines provides a rapid access to the ring-A-substituted tryptophans in good to excellent yields.
- Jia, Yanxing,Zhu, Jieping
-
p. 7826 - 7834
(2007/10/03)
-
- Deprotection of heteroaromatic carbamates via a base-catalyzed methanolysis
-
A simple and mild method for the deprotection of heteroaromatic carbamates via methanolysis using a catalytic amount of base such as sodium methoxide, DBU, or Verkade's base (proazaphosphatranes) is presented. Carbamate protecting group of an aliphatic amine is not affected under these conditions.
- Shieh, Wen-Chung,Xue, Song,McKenna, Joe,Prasad, Kapa,Repi?, Oljan,Blacklock, Thomas
-
p. 5645 - 5648
(2007/10/03)
-
- Synthesis of ring-A-substituted tryptophan by a palladium-catalyzed heteroannulation reaction
-
Coupling of substituted o-iodoanilines with methyl (S)-2-N,N-di-tert- butoxycarbonyl-5-oxo-pentanoate, derived from glutamic acid, in DMF in the presence of palladium acetate and DABCO provides substituted tryptophans in good to excellent yields. Georg Thieme Verlag Stuttgart.
- Jia, Yanxing,Zhu, Jieping
-
p. 2469 - 2472
(2007/10/03)
-
- Efficient chromatographic resolution of a configurationally fragile atropisomeric diphenol via its N-(α)-Boc-tryptophan diesters
-
Racemic 4,5-bis-(2-hydroxy-phenyl)-benzo[f]isoindole-1,3-dione 2, an atropisomeric diphenol prone to thermal isomerisation, has been efficiently resolved by conversion into its N-(α)-Boc-tryptophan diesters. Easy chromatographic separation of the diastereomeric pair of diesters, followed by ester cleavage under mild conditions gave each enantiomer in good yield and high enantiomeric purity. X-ray diffraction on a single crystal of one of the diastereomeric diesters allowed attribution of the absolute configuration of the stereogenic axes.
- Nechab, Malek,Panchal, Bhavesh M.,Philouze, Christian,Einhorn, Cathy,Einhorn, Jacques
-
p. 1681 - 1684
(2007/10/03)
-
- Polymer-supported mukaiyama reagent: A useful coupling reagent for the synthesis of esters and amides
-
(Chemical equation presented) Polymer-supported N-alkyl-2-chloro pyridinium triflate was synthesized in one step from Wang resin. This reagent proved to be a very effective coupling reagent for the synthesis of esters or amides from carboxylic acids and alcohols or amines (primary and secondary).
- Crosignani, Stefano,Gonzalez, Jerome,Swinnen, Dominique
-
p. 4579 - 4582
(2007/10/03)
-
- Ceric ammonium nitrate (CAN) mediated esterification of N-Boc amino acids allows either retention or removal of the N-Boc group
-
Reaction of N-Boc amino acids with ceric ammonium nitrate in an alcohol as the solvent at room temperature resulted in the esterification of N-Boc amino acids with Boc group retention. When the reaction was conducted at reflux temperature, esterification was accompanied with simultaneous removal of the Boc group. Both reactions gave the desired products in good yields.
- Kuttan, Ashani,Nowshudin, Shiek,Rao
-
p. 2663 - 2665
(2007/10/03)
-
- Synthesis and cell cycle inhibition of the peptide enamide natural products terpeptin and the aspergillamides
-
Total syntheses of the peptide enamide natural products terpeptin and aspergillamides A and B are reported. An oxidative decarboxylation-elimination protocol is employed to construct the indolic enamide moiety. Unambiguous stereochemical assignment of (-)-terpeptin is accomplished by synthesis of all possible stereochemical analogues. Select compounds have been evaluated in cell cycle inhibitor assays which show that the natural amino acid configuration of terpeptin has the most potent inhibitory activity.
- Su, Shun,Kakeya, Hideaki,Osada, Hiroyuki,Porco Jr., John A.
-
p. 8931 - 8946
(2007/10/03)
-
- Efficient and selective cleavage of t-butoxycarbonyl group from carbamates and amides by CeCl3·7H2O-NaI
-
A highly selective cleavage of the t-butoxycarbonyl group has been achieved in high yields using CeCl3·7H2O-NaI in acetonitrile at ambient temperature under neutral conditions. This method is mild and compatible with a wide range of
- Yadav,Subba Reddy,Reddy, K. Srinivasa
-
p. 468 - 470
(2007/10/03)
-
- Indium-mediated facile cleavage of the t-butoxycarbonyl group from di-t-butylimidodicarbonate
-
Di-t-butylimidodicarbonates are selectively and efficiently deprotected to the corresponding mono-BOC protected amines in high yields using indium or zinc metal in refluxing methanol. Simple BOC and CBz protected amines are unaffected by these conditions.
- Yadav,Reddy,Reddy, K.Srinivasa,Reddy, K.Bhaskar
-
p. 1549 - 1551
(2007/10/03)
-
- Does water suppress the racemization and decomposition of amino acids?
-
Several neutral free amino acids, phenylglycine, leucine, phenylalanine and tryptophan, are heated at 100-130 °C under alkaline or acidic conditions in water or various polar organic solvents. Although serious racemization and decomposition occur in polar organic solvents such as DMF, DMSO, or ethylene glycol under alkaline conditions (K2CO3, KOH, Et3N), these phenomena do not occur, or are largely decreased, in water or water-containing organic solvents under the same alkaline conditions. Serious racemization and decomposition of free phenylglycine are also observed in AcOH, while water or aqueous AcOH (90%) largely suppress the racemization and decomposition. We discuss the possible reasons for this suppression effect of water in terms of differential solvation of bases and states of dissociation of amino acids in aqueous and organic solvents.
- Yokoyama,Hikawa,Murakami
-
p. 1431 - 1434
(2007/10/03)
-
- Intramolecular inverse electron demand Diels-Alder reactions of tryptamine with tethered heteroaromatic azadienes
-
1,2,4,5-Tetrazines and 1,2,4-triazines tethered to tryptamine via the ethylamine side chain undergo intramolecular inverse electron demand cycloadditions to produce adducts with the [ABazaCE]-ring skeleton of the Aspidosperma alkaloids. (C) 2000 Elsevier Science Ltd.
- Benson, Scott C.,Lee, Lily,Yang, Lydie,Snyder, John K.
-
p. 1165 - 1180
(2007/10/03)
-
- A New and Efficient Synthesis of Unnatural Amino Acids and Peptides by Selective 3,3-Dimethyldioxirane Side-Chain Oxidation
-
N-Boc derivatives of Leu, Met, Thr, Trp, and Pro, the properties of which resemble those of the respective α-amino acid residues present in proteins, rapidly oxidize in the presence of 3,3-dimethyldioxirane to give different products depending on the stru
- Saladino, Raffaele,Mezzetti, Maurizio,Mincione, Enrico,Torrini, Ines,Paradisi, Mario Paglialunga,Mastropietro, Gaia
-
p. 8468 - 8474
(2007/10/03)
-
- Synthesis of New Chiral Auxiliaries Derived from (S)-Tryptophan
-
The synthesis of chiral aminoalcohols 4 derived from (S)-tryptophan is described, by reaction of the protected amino acid 3 with various Grignard reagents.The aminoalcohols were transformed into the corresponding oxazolidin-2-ones 2 and acylated with 2-butenoyl chloride and 2-hexenoyl chloride, affording the imides 5a-e.The conformational analysis of both the oxazolidin-2-ones 2 and the Michael acceptors 5 was performed by means of 1H NMR, NOEDIF experiments and semiempirical AM1 calculations.
- Cardillo, Giuliana,Gentilucci, Luca,Tomasini, Claudia,Tomasoni, Laura
-
p. 1947 - 1956
(2007/10/03)
-
- Reductive cleavage of TROC groups under neutral conditions with cadmium-lead couple
-
Cadmium-lead couple induces rapid and efficient reductive cleavage of TROC groups under extremely mild conditions. The couple is readily prepared and it is not pyrophoric.
- Dong, Qing,Anderson, C. Eric,Ciufolini, Marco A.
-
p. 5681 - 5682
(2007/10/02)
-
- The Synthesis of Optically Pure β-Cyclopiazonic Acid, an Indolic Fungal Metabolite
-
The chiral synthesis of the fungal metabolite β-cyclopiazonic acid is described.The key step involves the use of the tricarbonylchromium complex of an N-protected L-tryptophan methyl ester as a substrate for the addition/oxidation method of substitution o
- Holzapfel, Cedric W.,Kruger, Friedrich W. H.
-
-
- CONSTRUCTION OF OPTICALLY PURE TRYPTOPHANS FROM SERINE DERIVED AZIRIDINE-2-CARBOXYLATES
-
The possibility of preparing optically pure tryptophan derivatives from various substituted indoles and (2R)- or (2S)-2-aziridinecarboxylates has been examined.Zinc triflate was found to be the only Lewis acid capable of bringing about this reaction in mo
- Sato, Kazuo,Kozikowski, Alan P.
-
p. 4073 - 4076
(2007/10/02)
-
- Synthesis, Properties, and Use of Nin-Boc-tryptophan Derivatives
-
Nin-Boc-protected tryptophan derivatives can be prepared with Boc2O-4-dimethylaminopyridine in MeCN; their properties and utility are demonstrated in the synthesis of a tryptophan-containing tetrapeptide related to substance P.
- Franzen, Henry,Grehn, Leif,Ragnarsson, Ulf
-
p. 1699 - 1700
(2007/10/02)
-
- TRICARBONYLCHROMIUM TRYPTOPHAN DERIVATIVES AND THEIR USE IN PEPTIDE SYNTHESIS
-
Incorporation of a Cr(CO)3 ligand into the indole ring of N-α-t-butoxycarbonyl * tryptophan methyl ester was achieved in 47percent yield.The corresponding para-nitrophenyl ester was used in the solid phase synthesis of a peptidic hormone (LHRH) analogue with the aim of decreasing tryptophan alkylation.No improvement was observed.
- Sergheraert, C.,Tartar, A.
-
p. 163 - 168
(2007/10/02)
-
