cas 14898-52-3, methyl 3-amino-3-phenylpropanoate

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β-Amino esters via the Reformatsky reaction: Restraining effects of the ortho-methoxyphenyl substituent
β-Amino esters are, in most cases, the only products of the Reformatsky reaction in CH2Cl2 between (methoxycarbonyl)methyl zinc bromide (prepared in-situ) and imines prepared from either an aryl or alkyl aldehyde and o- anisdine (Sch
Adrian Jr., James C.,Barkin, Julia L.,Hassib, Lamyaa
p. 2457 - 2460
(1999)
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Structure-Based Design and Development of Chemical Probes Targeting Putative MOR-CCR5 Heterodimers to Inhibit Opioid Exacerbated HIV-1 Infectivity
Crystal structures of ligand-bound G-protein-coupled receptors provide tangible templates for rationally designing molecular probes. Herein, we report the structure-based design, chemical synthesis, and biological investigations of bivalent ligands targeting putative mu opioid receptor C-C motif chemokine ligand 5 (MOR-CCR5) heterodimers. The bivalent ligand VZMC013 possessed nanomolar level binding affinities for both the MOR and CCR5, inhibited CCL5-stimulated calcium mobilization, and remarkably improved anti-HIV-1BaL activity over previously reported bivalent ligands. VZMC013 inhibited viral infection in TZM-bl cells coexpressing CCR5 and MOR to a greater degree than cells expressing CCR5 alone. Furthermore, VZMC013 blocked human immunodeficiency virus (HIV)-1 entry in peripheral blood mononuclear cells (PBMC) cells in a concentration-dependent manner and inhibited opioid-accelerated HIV-1 entry more effectively in phytohemagglutinin-stimulated PBMC cells than in the absence of opioids. A three-dimensional molecular model of VZMC013 binding to the MOR-CCR5 heterodimer complex is constructed to elucidate its mechanism of action. VZMC013 is a potent chemical probe targeting MOR-CCR5 heterodimers and may serve as a pharmacological agent to inhibit opioid-exacerbated HIV-1 entry.
Huang, Boshi,Wang, Huiqun,Zheng, Yi,Li, Mengchu,Kang, Guifeng,Barreto-De-Souza, Victor,Nassehi, Nima,Knapp, Pamela E.,Selley, Dana E.,Hauser, Kurt F.,Zhang, Yan
p. 7702 - 7723
(2021/06/28)

Transition Metal-Free N-Arylation of Amino Acid Esters with Diaryliodonium Salts
A transition metal-free approach for the N-arylation of amino acid derivatives has been developed. Key to this method is the use of unsymmetric diaryliodonium salts with anisyl ligands, which proved important to obtain high chemoselectivity and yields. The scope includes the transfer of both electron deficient, electron rich and sterically hindered aryl groups with a variety of different functional groups. Furthermore, a cyclic diaryliodonium salt was successfully employed in the arylation. The N-arylated products were obtained with retained enantiomeric excess.
Kervefors, Gabriella,Kersting, Leonard,Olofsson, Berit
supporting information
p. 5790 - 5795
(2021/03/08)

Carbon Dioxide-Mediated C(sp2)-H Arylation of Primary and Secondary Benzylamines
C-C bond formation by transition metal-catalyzed C-H activation has become an important strategy to fabricate new bonds in a rapid fashion. Despite the pharmacological importance of ortho-arylbenzylamines, however, effective ortho-C-C bond formation of free primary and secondary benzylamines using PdII remains an outstanding challenge. Presented herein is a new strategy for constructing ortho-arylated primary and secondary benzylamines mediated by carbon dioxide (CO2). The use of CO2 with Pd is critical to allowing this transformation to proceed under relatively mild conditions, and mechanistic studies indicate that it (CO2) is directly involved in the rate-determining step. Furthermore, the milder temperatures furnish free amine products that can be directly used or elaborated without the need for deprotection. In cases where diarylation is possible, an interesting chelate effect is shown to facilitate selective monoarylation.
Kapoor, Mohit,Chand-Thakuri, Pratibha,Young, Michael C.
supporting information
p. 7980 - 7989
(2019/05/22)

Intermolecular Radical C(sp3)?H Amination under Iodine Catalysis
The direct amination of aliphatic C?H bonds has remained one of the most tantalizing transformations in organic chemistry. Herein, we report on a unique catalyst system, which enables the elusive intermolecular C(sp3)?H amination. This practical synthetic strategy provides access to aminated building blocks and fosters innovative multiple C?H amination within a new approach to aminated heterocycles. The synthetic utility is demonstrated by the synthesis of four relevant pharmaceuticals.
Bosnidou, Alexandra E.,Mu?iz, Kilian
supporting information
p. 7485 - 7489
(2019/04/30)

Design, synthesis and structure-activity relationship of a focused library of β-phenylalanine derivatives as novel eEF2K inhibitors with apoptosis-inducing mechanisms in breast cancer
Eukaryotic elongation factor 2 kinase (eEF2K) is a Ca2+/calmudulin-dependent protein kinase, belonging to a small family of an atypical Ser/Thr-protein kinase. eEF2K has been recently reported to be highly activated or overexpressed in many types of cancer; therefore, eEF2K would be regarded as a promising therapeutic target. In this study, we discovered a β-phenylalanine scaffold by virtual high-throughput screening, as well as designed and synthesized 46 derivatives with assessment of inhibition activity against eEF2K and cytotoxicity. After several rounds of kinase and anti-proliferative activity screening, we discovered an eEF2K inhibitor (21l) with best eEF2K enzymatic activity (IC50 of 5.5 μM) and anti-proliferative activity (MDA-MB-231 cells, IC50 of 12.6 μM, MDA-MB-436 cells, IC50 of 19.8 μM). Moreover, we found that 21l could induce cell death via the apoptotic pathways in MDA-MB-231 and MDA-MB-436 cells. Subsequently, we evaluated its anti-tumor activity and apoptosis-inducing mechanisms in vivo. These results suggested that 21l inhibited tumor growth by apoptosis in the xenograft mouse model of breast cancer (MDA-MB-231 and MDA-MB-436). Collectively, our results demonstrate a novel small-molecule inhibitor targeting eEF2K with mechanism of apoptosis and a therapeutic potential in breast cancer.
Guo, Yongzhi,Zhao, Yuqian,Wang, Guan,Chen, Yi,Jiang, Yingnan,Ouyang, Liang,Liu, Bo
p. 402 - 418
(2017/12/07)

Preparation and application of novel eEF2K depressant
The invention relates to preparation and application of an eEF2K depressant and belongs to the technical field of antitumor pharmacy. A technical problem to be solved by the invention is to provide acompound as the eEF2K depressant. The compound comprises a compound represented by a formula shown in the description or pharmaceutically acceptable salts thereof. The compound or pharmaceutically acceptable salts thereof can serve as the eEF2K depressant, have certain anti-tumor activity and can effectively depress the growth of cancer cells. The compound disclosed by the invention has an obviousdepression action on a variety of tumor cells, particularly three-negative mammary cancer cells.
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Paragraph 0051-0053

(2018/05/01)

HETEROARYL-CARBOXAMIDES AS HISTONE DEMETHYLASE INHIBITORS
The invention relates to heteroaryl-carboxamides as described herein, useful as histone demethyiase inhibitors. The invention also relates to pharmaceutical compositions comprising these compounds and to their use in therapy, including e.g., in the treatment of cancer.
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Page/Page column 79

(2019/01/04)

HETEROARYL-CARBOXYLIC ACIDS AS HISTONE DEMETHYLASE INHIBITORS
The invention relates to heteroaryl-carboxylic acids as described herein, useful as histone demethylase inhibitors. The invention also relates to pharmaceutical compositions comprising these compounds and to their use in therapy, including e.g., in the treatment of cancer.
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Page/Page column 84

(2018/01/17)

Chiral 6-aryl-furo[2,3-d]pyrimidin-4-amines as EGFR inhibitors
Epidermal growth factor receptor inhibitors are of importance in cancer therapy and possibly in the management of pain. Herein, we report a structure-activity relationship study with 29 new 6-aryl-furo[2,3-d]pyrimidin-4-amines, involving modification of the 4-amino group and 6-aryl function. The EGFR activity was especially dependent on having a chiral 4-benzylamino group with correct stereochemistry. Molecular dynamics indicate this to be due to favourable cation-π interactions. The most active inhibitor identified, equipotent to Erlotinib, was substituted with (R)-1-phenylethylamine at C-4 and a N1, N1-dimethyl-1,2-diamine group in para position of the 6-aryl moiety. These new furopyrimidines had a different off-target kinase profile when compared to Erlotinib, and also possessed high activity towards Ba/F3 EGFRL858R reporter cells. Further, comparing the EGFR data of the furo[2,3-d]pyrimidin-4-amines with that of the corresponding thieno- and pyrrolopyrimidines concludes the furopyrimidine scaffold to be highly useful for development of new epidermal growth factor receptor antagonists.
Han, Jin,Kaspersen, Svein Jacob,Nervik, Sondre,N?rsett, Kristin G.,Sundby, Eirik,Hoff, B?rd Helge
p. 278 - 299
(2016/06/14)

One-pot synthesis process of 3-amino-3-phenyl propionate
The invention discloses a one-pot synthesis process of 3-amino-3-phenyl propionate shown in the formula (II). Benzaldehyde shown in the formula (I), malonic acid and ammonium acetate serve as raw materials and react in a solvent, and then the product reacts with an esterification reagent to synthesize 3-amino-3-phenyl propionate shown in the formula (II) through a one-pot method. All the reaction raw materials are put in a reaction still to react, and 3-amino-3-phenyl propionate is synthesized through the one-pot method by selecting proper reaction conditions. The process is high in selectivity, intermediate products do not need to be separated, the yield is high, fewer impurities are generated, safety and environment friendliness are achieved, operation is easy, and practical value is high. The formula (I) and the formula (II) are shown in the specification.
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Paragraph 0018

(2017/06/13)

Carica papaya lipase catalysed resolution of β-amino esters for the highly enantioselective synthesis of (S)-dapoxetine
An efficient synthesis of the (S)-3-amino-3-phenylpropanoic acid enantiomer has been achieved by Carica papaya lipase (CPL) catalysed enantioselective alcoholysis of the corresponding racemic N-protected 2,2,2-trifluoroethyl esters in an organic solvent. A high enantioselectivity (E > 200) was achieved by two strategies that involved engineering of the substrates and optimization of the reaction conditions. Based on the resolution of a series of amino acids, it was found that the structure of the substrate has a profound effect on the CPL-catalysed resolution. The enantioselectivity and reaction rate were significantly enhanced by switching the conventional methyl ester to an activated trifluoroethyl ester. When considering steric effects, the substituted phenyl and amino groups should not both be large for the CPL-catalysed resolution. The mechanism of the CPL-catalysed enantioselective alcoholoysis of the amino acids is discussed to delineate the substrate requirements for CPL-catalysed resolution. Finally, the reaction was scaled up, and the products were separated and obtained in good yields (≥ 80 %). The (S)-3-amino-3- phenylpropanoic acid obtained was used as a key chiral intermediate in the synthesis of (S)-dapoxetine with very high enantiomeric excess (> 99 %). A carica papaya lipase catalysed resolution of N-protected β-phenylalanine esters has been developed. High enantioselectivity was achieved by two strategies that involved engineering of the substrates and optimization of the reaction conditions. After 50 % conversion, the products were separated and used as key chiral intermediates for the synthesis of (S)-dapoxetine with > 99 % ee. Copyright
You, Pengyong,Qiu, Jian,Su, Erzheng,Wei, Dongzhi
p. 557 - 565
(2013/03/13)

Asymmetric biocatalysis of S-3-amino-3-phenylpropionic acid with new isolated Methylobacterium Y1-6
β-amino acids are widely used in drug research, and S-3-amino-3-phenylpropionic acid (S-APA) is an important pharmaceutical intermediate of S-dapoxetine, which has been approved for the treatment of premature ejaculation. Chiral catalysis is an excellent method for the preparation of enantiopure compounds. In this study, we used (±)-ethyl-3-amino-3-phenylpropanoate (EAP) as the sole carbon source. Three hundred thirty one microorganisms were isolated from 30 soil samples, and 17 strains could produce S-APA. After three rounds of cultivation and identification, the strain Y1-6 exhibiting the highest enantioselective activity of S-APA was identified as Methylobacterium oryzae. The optimal medium composition contained methanol (2.5 g/L), 1,2-propanediol (7.5 g/L), soluble starch (2.5 g/L), and peptone (10 g/L); it was shaken at 220 rpm for 4-5 days at 30 C. The optimum condition for biotransformation of EAP involved cultivation at 37 C for 48 h with 120 mg of wet cells and 0.64 mg of EAP in 1 ml of transfer solution. Under this condition, substrate ee was 92.1% and yield was 48.6%. We then attempted to use Methylobacterium Y1-6 to catalyze the hydrolytic reaction with substrates containing 3-amino-3-phenyl-propanoate ester, N-substituted-β-ethyl-3-amino-3-phenyl-propanoate, and γ-lactam. It was found that 5 compounds with ester bonds could be stereoselectively hydrolyzed to S-acid, and 2 compounds with γ-lactam bonds could be stereoselectively hydrolyzed to (-)-γ-lactam.
Li, Yi,Wang, Wenfu,Huang, Yumian,Zou, Qianwen,Zheng, Guojun
p. 1674 - 1678
(2013/11/19)

Stereoselective chemoenzymatic preparation of β-amino esters: Molecular modelling considerations in lipase-mediated processes and application to the synthesis of (S)-dapoxetine
A wide range of optically active 3-amino-3-arylpropanoic acid derivatives have been prepared by means of a stereoselective chemoenzymatic route. The key step is the kinetic resolution of the corresponding β-amino esters. Although the enzymatic acylations of the amino group with ethyl methoxyacetate showed synthetically useful enantioselectivities, the hydrolyses of the ester group catalyzed by lipase from Pseudomonas cepacia have been identified as the optimal processes concerning both activity and enantioselectivity. The enantiopreference of this lipase in these reactions has been explained, at the molecular level, by using a fragment-based approach in which the most favoured binding site for a phenyl ring and the most stable conformation of the 3-aminopropanoate core nicely match the (S)-configuration of the major products. The conversion and enantioselectivity values of the enzymatic reactions have been compared in order to understand the influence of the different substitution patterns present in the phenyl ring. This chemoenzymatic route has been successfully applied to the preparation of a valuable intermediate in the synthesis of (S)-dapoxetine, which has been chemically synthesised in excellent optical purity.
Rodriguez-Mata, Maria,Garcia-Urdiales, Eduardo,Gotor-Fernandez, Vicente,Gotor, Vicente
supporting information; experimental part
p. 395 - 406
(2010/06/15)

Substituted Spiroamine Compounds
Substituted spiroamine compounds corresponding to the formula (I) In which m, n, o, p, Q, r, s, t, R1, R2, R3, R4a, R4b, R5a, R5b, R6a, R6b, R7, R8, R9, R10 and R11 have defined meanings; a process for the preparation of such compounds, pharmaceutical compositions containing such compounds and the use of substituted spiroamines for the treatment or inhibition of pain and/or other conditions mediated by the bradykinin 1 receptor.
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Page/Page column 50-51

(2010/05/13)

Synthesis, in vitro and in vivo biological evaluation, and comprehensive understanding of structure-activity relationships of dipeptidyl boronic acid proteasome inhibitors constructed from β-amino acids
An extensive structure-activity relationship (SAR) study of 72 dipeptidyl boronic acid proteasome inhibitors constructed fromβ -amino acids is reported. SAR analysis revealed that bicyclic groups at the R1 position, 3-F substituents at the Rsu
Zhu, Yongqiang,Wu, Gang,Zhu, Xinrong,Ma, Yuheng,Zhao, Xin,Li, Yuejie,Yuan, Yunxia,Yang, Jie,Yu, Sen,Shao, Feng,Lei, Meng
supporting information; experimental part
p. 8619 - 8626
(2011/03/20)

Isomer differentiation via collision-induced dissociation: The case of protonated a-, β2- and β3-phenylalanines and their derivatives
A combination of electrospray ionisation (ESI), multistage and high-resolution mass spectrometry experiments is used to examine the gas-phase fragmentation reactions of the three isomeric phenylalanine derivatives, a-phenylalanine, b2-phenylalanine and b3-phenylalanine. Under collision-induced dissociation (CID) conditions, each of the protonated phenylalanine isomers fragmented differently, allowing for differentiation. For example, protonated b3-phenylalanine fragments almost exclusively via the loss of NH3, only b2-phenylalanine via the loss of H2O, while a- and b2- phenylalanine fragment mainly via the combined losses of H2ORCO. Density functional theory (DFT) calculations were performed to examine the competition between NH3 loss and the combined losses of H2O and CO for each of the protonated phenylalanine isomers. Three potential NH3 loss pathways were studied: (i) an aryl-assisted neighbouring group; (ii) 1,2 hydride migration; and (iii) neighbouring group participation by the carboxyl group. Finally, we have shown that isomer differentiation is also possible when CID is performed on the protonated methyl ester and methyl amide derivatives of a-, b2- and b3-phenylalanines.
Lam, Adrian K. Y.,O'Hair, Richard A. J.
experimental part
p. 1779 - 1790
(2011/11/05)

A versatile catalyst for reductive animation by transfer hydrogenation
An iridium catalyst enables the reductive amination of carbonyl groups with unprecedented substrate scope, selectivity, and activity using formic acid as the hydrogen source (see scheme) The catalyst system provides significant improvement over commonly used boron hydrides.
Wang, Chao,Pettman, Alan,Basca, John,Xiao, Jianliang
supporting information; experimental part
p. 7548 - 7552
(2010/12/19)

Substituted Sulfonamide Compounds
Substituted sulfonamide compounds corresponding to the formula I wherein m, n, p, Q, R1, R2, R3, R4, X, Y and Z have the respective meanings defined herein, pharmaceutical compositions containing such compounds, a process for their preparation, and the use of such compounds for the treatment and/or inhibition of pain and other conditions mediated by bradykinin receptor 1 (B1R) and/or bradykinin receptor 2 (B2R).
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Page/Page column 28

(2009/07/25)

Substituted Sulfonamide Compounds
Substituted sulfonamide compounds corresponding to the formula I: processes for the preparation thereof, pharmaceutical composition containing these compounds and the use of substituted sulfonamide compounds for the preparation of pharmaceutical compositions.
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Page/Page column 44

(2009/10/17)

SUBSTITUTED SULFONAMIDE COMPOUNDS
Substituted sulfonamide compounds corresponding to formula I processes for the preparation thereof, pharmaceutical compositions containing these compounds, and the use of such substituted sulfonamide compounds in pharmaceutical compositions for the treatment and/or inhibition of pain and other conditions at least partly mediated by the bradykinin 1 receptor
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Page/Page column 30

(2009/10/30)

Substituted Sulfonamide Compounds
Substituted sulfonamide compounds corresponding to formula I: a process for their preparation, pharmaceutical compositions comprising such compounds, and the use of such substituted sulfonamide compounds in pharmaceutical compositions for the treatment of pain or other disorders or diseases that are mediated at least in part by B1R receptors.
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Page/Page column 25

(2009/10/30)

SUBSTITUTED SULFONAMIDE DERIVATIVES
The invention relates to substituted sulfonamide derivatives, processes for the preparation thereof, medicaments containing these compounds and the use of substituted sulfonamide derivatives for the preparation of medicaments.
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Page/Page column 61

(2009/10/22)

PYRROLINE DERIVATIVES AGAINST CELL RELEASING TUMOR NECROSIS FACTOR, PREPARATION METHODS AND USES THEREOF
Compounds represented by Formula (I) or Formula (II) against cell releasing TNFα, their pharmaceutically acceptable salts or hydrates and preparation methods and uses thereof, in which A and B represent CH2, CO, SO, or SO2; D represents S, NH, or NC1-6 alkyl; R1 represents H, or one or two same or different radical(s) selected from the group consisting of F, Cl, Br, C1-4 alkyl,OH,OC1-4 alkyl,NO2,NHC(O)C1-4 alkyl,NH2,NH(C1-4 alkyl), or N(C1-4 alkyl)2.
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Page/Page column 13

(2009/08/14)

Substituted Sulfonamide Compounds
Substituted sulfonamide compounds corresponding to formula I pharmaceutical compositions comprising them, a process for preparing them, and the use of such compounds to treat or inhibit pain and other disorders or disease states.
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Page/Page column 42

(2009/01/24)

Discovery of a novel CCR5 antagonist lead compound through fragment assembly
CCR5, as the major co-receptor for HIV-1 entry, is an attractive novel target for the pharmaceutical industry in the HIV-1 therapeutic area. In this study, based on the structures of maraviroc and 1,4-bis(4-(7-chloroquinolin-4- yl)piperazin-1-yl)butane-1,4-dione (1), which was identified using structure-based virtual screening in conjunction with a calcium mobilization assay, a series of novel small molecule CCR5 antagonists have been designed and synthesized through fragment assembly. Preliminary SARs were obtained, which are in good agreement with the molecular binding model and should prove helpful for future antagonist design. The novel scaffold presented here might also be useful in the development of maraviroc-derived second generation CCR5 antagonists.
Liu, Yanqing,Zhou, Enkun,Yu, Kunqian,Zhu, Jin,Zhang, Yu,Xie, Xin,Li, Jian,Jiang, Hualiang
experimental part
p. 2426 - 2441
(2009/04/11)

Development of a bulk enabling route to maraviroc (UK-427,857), a CCR-5 receptor antagonist
A bulk enabling synthesis of the CCR-5 receptor antagonist, Maraviroc (UK-427,857) (1), is presented. Synthesis of the three key fragments, β-amino ester 3,4,4-difluorohexanecarboxylic acid (2), and 1,3,4-triazole-substituted tropane fragment 4 are described. Coupling strategies for these fragments are discussed and described, including synthetic challenges, protection strategies, impurity generation, and final scale-up of the developed route to 1.
Haycock-Lewandowski, Sarah J.,Wilder, Alexander,Ahman, Jens
p. 1094 - 1103
(2013/01/03)

Structures of β-amino ester enolates: New strategies using the method of continuous variation
The solution structures of four enolates derived from β-amino esters are investigated using 6Li NMR spectroscopy in conjunction with the method of continuous variation (method of Job). Ensembles of homo- and heteroaggregated enolates are generated by mixing enantiomers ofa single enolate (R/S mixtures), opposite antipodes of two different en olates (R/S mixtures), and the same antipodes of two different enolates (RIR mixtures). The numbers of observable aggregates and their dependence on the mole fraction of the two enolates confirm the hexamer assignments. Inherent symmetries observable in the 6Li NMR spectra show the stereochemistry of chelation about the hexagonal drum.
Liou, Lara R.,McNeil, Anne J.,Toombes, Gilman E. S.,Collum, David B.
supporting information; experimental part
p. 17334 - 17341
(2009/09/07)

Highly Diastereoselective Heterogeneously Catalyzed Hydrogenation of Enamines for the Synthesis of Chiral β-Amino Acid Derivatives
Pure (Z)-enamines readily prepared from β-ketoesters and amides using (S)-phenylglycine amide were hydrogenated with very high diastereoselectivities (up to 200:1) using heterogeneous catalysis. Hydrogenolytic cleavage of the (S)-phenylglycine amide afforded the corresponding chiral β-aminoesters and amides. The high geometrical purity of the (Z)-enamine and a simple activation procedure for the PtO2 catalyst are essential in achieving high selectivity. Copyright
Ikemoto, Norihiro,Tellers, David M.,Dreher, Spencer D.,Liu, Jinchu,Huang, Angie,Rivera, Nelo R.,Njolito, Eugenia,Hsiao, Yi,McWilliams, J. Christopher,Williams, J. Michael,Armstrong III, Joseph D.,Sun, Yongkui,Mathre, David J.,Grabowski, Edward J. J.,Tillyer, Richard D.
p. 3048 - 3049
(2007/10/03)

Method for producing an optically active beta-amino acid
To provide a producing method of an optically active β-amino acid useful as intermediate for the production of medicines, agricultural chemicals and physiologically active substances, by means of a catalytic and asymmetric synthesis method of high performance and a high enantiomeric excess, without requiring additional procedures such as introduction and removal of protecting group and so on. A producing method of an optically active β-amino acids which comprises subjecting an enamine to an asymmetric hydrogenation.
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Page 14

(2010/02/06)

Dutch Resolution: Separation of enantiomers with families of resolving agents. A status report
Dutch Resolution is the term given to the use of mixtures (families) of resolving agents in classical resolutions. In this status report an overview is given of the latest results and new (possible) families of resolving agents are introduced. The concept of families is discussed as well as the factors that come into play on use of families. Practical aspects of Dutch Resolution in particular and resolutions in general are discussed.
Kellogg, Richard M.,Nieuwenhuijzen, Jose W.,Pouwer,Vries, Ton R.,Broxterman, Quirinus B.,Grimbergen, Reinier F.P.,Kaptein, Bernard,La Crois, Rene M.,De Wever, Ellen,Zwaagstra, Karen,Van Der Laan, Alexander C.
p. 1626 - 1638
(2007/10/03)

An allyltitanium derived from acrolein 1,2-dicyclohexylethylene acetal and (η2-propene)Ti(o-i-Pr)2 as a chiral propionaldehyde homoenolate equivalent that reacts with imines with excellent stereoselectivity. An efficient and practical access to optically active γ-amino carbonyl compounds
A chiral allyltitanium compound 2, prepared in situ by the reaction of optically active acrolein 1,2-dicyclohexylethylene acetal (3) with (η2-propene)Ti(O-i-Pr)2 (1), reacts with a variety of acyclic and cyclic imines 4 in a regiospecific way to afford α-addition products 5 as a mixture of the E- and Z-isomers in good combined yield, where the former is predominant in a ratio of 92: 8 to >95:5. The mixture of (E)- and (Z)-5 and pure (E)-5 which could be isolated in several cases were respectively converted to the corresponding β-amino ester 6 to confirm the absolute configuration and enantiomeric purity. The ee of the newly formed asymmetric center of 5 is more than 78% for the mixture of (E)- and (Z)-5 and more than 96% for pure (E)-5. By taking advantage of the versatility of the vinyl ether moiety in 5, optically active γ-amino aldehydes 8, γ-amino aldehyde acetals 7 and 10, γ-amino acids 9, β-amino esters 6, and pyrrolidinoisoquinolines 12 were readily prepared. In the reaction of 2 with optically active α-silyloxyimine 4n, remarkable double stereodifferentiation was observed; thus, the reaction of 2 derived from (S,S)- or (R,R)-3 provided syn- and anti-5n in a ratio of 55:45 or 0:100, respectively. Meanwhile, the stereochemistry of the product in the reaction of 2 with β-silyloxyimine 4o was controlled mainly by 2. Thus, the reaction of β-silyloxyimine 14 with 2 derived from 1 and (R,R)-3 afforded γ-silyloxyimine 15 with 92% diastereoselectivity, from which 4-amino6-hydroxypentadecanal dimethyl acetal (13), a key intermediate for the synthesis of batzelladine D, was synthesized.
Okamoto,Teng,Fujii,Takayama,Sato
p. 3462 - 3471
(2007/10/03)

Synthesis, X-ray crystal-structure analysis, and NMR studies of (η3- allyl)palladium(II) complexes containing a novel dihydro(phosphinoaryl)oxazine ligand: Application in palladium-catalyzed asymmetric synthesis
The novel chiral P,N-ligand 2-[2-(diphenylphosphino)phenyl]-5,6-dihydro- 4-phenyl-4H-1,3-oxazine (4) was synthesized. The corresponding {dihydro[(phosphino-κP)aryl]oxazine-κN} (η3-diphenylallyl)palladium(II) hexafluorophosphate 5 and the analogous [Pd(η3-1,3-dimethylallyl)] complex 6 were investigated by X-ray analysis and 1D- and 2D-NMR spectroscopy. The complex 5 exists as 'exo'-syn-syn isomer in the solid state (Fig. 1). In solution, the same isomer exceeds with 90%. The X-ray crystal structure of 6 reveals that the dihydro(phosphinoaryl)oxazine ligand coordinates in a pseudo-enantiomeric conformation compared with that of 5 (Fig. 3). A syn-anti arrangement of the allyl substituents of 6 is favored in the solid state. 1H-NMR Spectroscopic investigations suggest that the auxiliary 6 adopts two conformations. This conformational instability together with 'exo'/'endo' and syn/anti isomerization leads to the formation of 6 isomers (Fig. 4). The asymmetric allylic substitution reaction of 1,3-diphenylallyl acetate with dimethyl malonate in the presence of 4 proceeds with a selectivity of 99% ee. The ee induced by 4 in the catalytic allylic substitution of 1-methylbut-2- enyl acetate is moderate (54%).
Liu, Shuangying,Mueller, Juergen F. K.,Neuburger, Markus,Schaffner, Silvia,Zehnder, Margareta
p. 1256 - 1267
(2007/10/03)

Combinatorial Synthesis of 2-Thioxo-4-dihydropyrimidinones
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Sim, Mui Mui,Lee, Cheng Leng,Ganesan, Arasu
p. 9358 - 9360
(2007/10/03)

95. Asymmetric synthesis of the alkaloids mayfoline and N(1)-Acetyl-N(1)-deoxymayfoline
The total syntheses of the spermidine alkaloids (-)-mayfoline (11) and (+)-N(1)-acetyl-N(1)-deoxymayfoline (12) are described. These macrocyclic lactams belong to the most interesting conjugates of the polyamine derivatives very commonly found in nature. The enantioselective syntheses were achieved through resolution of the methyl 3-amino-3-phenylpropanoate (2) by recrystallization of its (+)-L-tartrate salt. Construction of the 13-membered ring ensued through condensation, reductive ring expansion (internal bond cleavage), and finally a transamidation reaction involving a second ring expansion.
Kuehne, Paul,Linden, Anthony,Hesse, Manfred
p. 1085 - 1094
(2007/10/03)

A β,β,β-Trialkoxyethyllithium Stable towards Fragmentation: a Carboxyl Protected Acetic Acid Dianion Equivalent
The novel alkyllithium 1b is not only intriguinly stable towards fragmentation, but also a synthetically useful reagent, complementing current carboxylic ester enolate methodology.Its design is based on interesting mechanistic principles, and harnesses the known stability of the 2,4,10-trioxaadamantane framework.
Chandrasekhar, Sosale,Roy, Chandra Deo
p. 8099 - 8102
(2007/10/02)

A convenient diastereoselective total synthesis of andrimid
A convenient diastereoselective synthesis of andrimid was accomplished in a straightforward approach and also several β-substituted cyclic imides were prepared in a facile manner.
Rama Rao,Singh,Varaprasad
p. 4393 - 4396
(2007/10/02)

THE USE OF β-LACTAMS IN THE SYNTHESIS OF SPERMINE AND SPERMIDINE ALKALOIDS. TOTAL SYNTHESIS OF HOMALINE
The optically active plant product homaline (6) has been synthesized in a convergent sequence starting with β-phenyl-β-alanine and putrescine (14).The key transformation in this sequence is the ring expansion by transamidation of a functionalized chiral β-lactam precursor.
Wasserman, Harry H.,Berger, Gregory D.
p. 2459 - 2464
(2007/10/02)