- Methyl 2-[(tert-Butoxycarbonyl)amino]-3-hydroxy-3-phenylpropanoate: Synthesis of Erythro (±) Isomer by Reduction and Threo (±) Isomer by Inversion Method
-
Abstract: We report an efficient protocol for synthesis of methyl 2-[(tert-butoxycarbonyl) amino]-3-hydroxy-3-phenylpropanoate (Erythro (±)) by simple reduction and methyl 2-[(tert-butoxycarbonyl) amino]-3-hydroxy-3-phenylpropanoate (Threo (±)) by inversi
- Giri Prasad, M.,Jonnalagadda, Sreekantha B.,Katari, Naresh Kumar,Kerru, Nagaraju,Rekulapally, Vijay Kumar,Vijaya Lakshmi, C.
-
p. 2539 - 2545
(2022/01/22)
-
- Total Synthesis and Antimycobacterial Activity of Ohmyungsamycin A, Deoxyecumicin, and Ecumicin
-
The ohmyungsamycin and ecumicin natural product families are structurally related cyclic depsipeptides that display potent antimycobacterial activity. Herein the total syntheses of ohmyungsamycin A, deoxyecumicin, and ecumicin are reported, together with the direct biological comparison of members of these natural product families against Mycobacterium tuberculosis (Mtb), the etiological agent of tuberculosis (TB). The synthesis of each of the natural products employed a solid-phase strategy to assemble the linear peptide precursor, involving a key on-resin esterification and an optional on-resin dimethylation step, before a final solution-phase macrolactamization between the non-proteinogenic N-methyl-4-methoxy-l-tryptophan amino acid and a bulky N-methyl-l-valine residue. The synthetic natural products possessed potent antimycobacterial activity against Mtb with MIC90’s ranging from 110–360 nm and retained activity against Mtb in Mtb-infected macrophages. Deoxyecumicin also exhibited rapid bactericidal killing against Mtb, sterilizing cultures after 21 days.
- Hawkins, Paige M. E.,Tran, Wendy,Nagalingam, Gayathri,Cheung, Chen-Yi,Giltrap, Andrew M.,Cook, Gregory M.,Britton, Warwick J.,Payne, Richard J.
-
p. 15200 - 15205
(2020/10/23)
-
- Total Synthesis of Ecumicin
-
The first total synthesis of the potent anti-mycobacterial cyclic depsipeptide natural product ecumicin is described. Synthesis was achieved via a solid-phase strategy, incorporating the synthetic non-proteinogenic amino acids N-methyl-4-methoxy-l-tryptophan and threo-β-hydroxy-l-phenylalanine into the growing linear peptide chain. The synthesis employed key on-resin esterification and dimethylation steps as well as a final macrolactamization between the unusual N-methyl-4-methoxy-l-tryptophan unit and a bulky N-methyl-l-valine residue. The synthetic natural product possessed potent antimycobacterial activity against the virulent H37Rv strain of Mycobacterium tuberculosis (MIC90 = 312 nM).
- Hawkins, Paige M. E.,Giltrap, Andrew M.,Nagalingam, Gayathri,Britton, Warwick J.,Payne, Richard J.
-
p. 1019 - 1022
(2018/02/23)
-
- A process for producing an intermediate agonist GRK 3
-
The present invention is directed to a process for preparing a compound of formula I-11 through multiple-step reactions.
- -
-
Paragraph 0114-0117
(2016/10/09)
-
- CHIRAL FLUORINATING REAGENTS
-
This invention relates to fluorinating agents and, more particularly, to chiral non-racemic fluorinating agents useful for enantioselective fluorination, as well as to their synthesis and use and other subject matter. The fluorinating agents are based on a substituted 1,4-diazabicyclo[2.2.2]octane (DABCO) skeleton and provide electrophillic fluorine enantioselectively.
- -
-
-
- Copper-catalyzed asymmetric hydroboration of α-dehydroamino acid derivatives: Facile synthesis of chiral β-hydroxy-α-amino acids
-
The Cu-catalyzed asymmetric conjugate hydroboration reaction of β-substituted α-dehydroamino acid derivatives has been established, affording enantioenriched syn- and anti-β-boronate-α-amino acid derivatives with excellent combined yields (83-99%, dr ≈ 1:
- He, Zhi-Tao,Zhao, Yi-Shuang,Tian, Ping,Wang, Chuan-Chuan,Dong, Han-Qing,Lin, Guo-Qiang
-
supporting information
p. 1426 - 1429
(2014/04/03)
-
- PROCESS FOR MAKING BETA 3 ANGONISTS AND INTERMEDIATES
-
The present invention is directed to a process for preparing a compound of formula I-11 through multiple-step reactions:.
- -
-
Page/Page column 15; 17; 24-26
(2013/05/21)
-
- Asymmetric synthesis of cis-2,5-disubstituted pyrrolidine, the core scaffold of β3-AR agonists
-
A practical, enantioselective synthesis of cis-2,5-disubstituted pyrrolidine is described. Application of an enzymatic DKR reduction of a keto ester, which is easily accessed through a novel intramolecular N→C benzoyl migration, yields syn-1,2-amino alcoh
- Xu, Feng,Chung, John Y. L.,Moore, Jeffery C.,Liu, Zhuqing,Yoshikawa, Naoki,Hoerrner, R. Scott,Lee, Jaemoon,Royzen, Maksim,Cleator, Ed,Gibson, Andrew G.,Dunn, Robert,Maloney, Kevin M.,Alam, Mahbub,Goodyear, Adrian,Lynch, Joseph,Yasuda, Nobuyashi,Devine, Paul N.
-
supporting information
p. 1342 - 1345
(2013/04/24)
-
- Asymmetric synthesis of 2,4,5-trisubstituted Δ2- thiazolines
-
Δ2-Thiazolines are interesting heterocycles that display a wide variety of biological characteristics. They are also common in chiral ligands used for asymmetric syntheses and as synthetic intermediates. Herein, we present asymmetric routes to
- Bengtsson, Christoffer,Nelander, Hanna,Almqvist, Fredrik
-
p. 9916 - 9922
(2013/08/23)
-
- Osmium-catalyzed vicinal oxyamination of alkenes by N-(4- toluenesulfonyloxy)carbamates
-
N-(4-Toluenesulfonyloxy)carbamates based on a range of common amine protecting groups serve as preformed nitrogen sources in the intermolecular osmium-catalyzed oxyamination reaction of a variety of mono-, di-, and trisubstituted alkenes. The reactions occur with low catalyst loadings and good yields and afford high regioselectivity for unsymmetrically substituted alkenes.
- Masruri,Willis, Anthony C.,McLeod, Malcolm D.
-
p. 8480 - 8491
(2012/11/13)
-
- Asymmetric transfer hydrogenation coupled with dynamic kinetic resolution in water: Synthesis of anti -β-hydroxy-α-amino acid derivatives
-
The use of asymmetric transfer hydrogenation combined with dynamic kinetic resolution for the synthesis of β-hydroxy-α-(tert-butoxycarbonyl) amino esters in water is described. This procedure provides the desired amino alcohols in good yields, diastereoselectivities, and enantioselectivities. A surfactant is employed to achieve good yields due to the hydrophobic nature of both the catalyst and substrate. The reaction setup is operationally simple, and nondegassed water can be used as the solvent.
- Seashore-Ludlow, Brinton,Saint-Dizier, Fran?ois,Somfai, Peter
-
supporting information
p. 6334 - 6337
(2013/02/23)
-
- Enantioselective synthesis of anti-β-hydroxy-α-amido esters by asymmetric transfer hydrogenation in emulsions
-
Herein, we present two methods for an asymmetric transfer hydrogenation through the dynamic kinetic resolution of α-amido-β-ketoesters. These procedures yield the corresponding anti-β-hydroxy-α-amido esters in good yields and with good diastereo- and enantioselectivities. First, the scope of the reduction of α-amido-β-ketoesters by using triethylammonium formate azeotrope is examined. Then, an emulsion technology with sodium formate is explored, which allows for broader substrate scope, faster reaction times, and lower catalyst loading. Furthermore, these reactions are operationally simple and can be set up in air.
- Seashore-Ludlow, Brinton,Villo, Piret,Somfai, Peter
-
supporting information; experimental part
p. 7219 - 7223
(2012/07/13)
-
- IMPROVED AMINOHYDROXYLATION OF ALKENES
-
The invention relates to a process for the aminohydroxylation of alkenes using N-oxycarbamate reagents, e.g. N-acyloxycarbamate, N-alkyloxycarbonyloxycarbamate and N-aralkoxycarbonyloxycarbamate reagents. The invention particularly relates to an intermolecular aminohydroxylation reaction that can be carried out in the absence of added base. The invention also relates to novel N-oxycarbamate reagents that are stable crystalline materials. The process of the invention is useful in the synthesis of compounds having a vicinal amino alcohol moiety, such as biologically active compounds.
- -
-
Page/Page column 59
(2012/01/06)
-
- Alkyl 4-chlorobenzoyloxycarbamates as highly effective nitrogen source reagents for the base-free, intermolecular aminohydroxylation reaction
-
Ethyl-(7), benzyl-(8), tert-butyl-(9), and fluorenylmethyl-4- chlorobenzoyloxycarbamates (10) have been prepared as storable and easy-to-prepare nitrogen sources for use in the intermolecular Sharpless aminohydroxylation reaction and its asymmetric variant. These reagents were found to be effective under base-free reaction conditions. The scope and limitations of these methods have been explored using a variety of alkenes, among which, trans-cinnamates, in particular, proved to be good substrates.
- Harris, Lawrence,Mee, Simon P. H.,Furneaux, Richard H.,Gainsford, Graeme J.,Luxenburger, Andreas
-
experimental part
p. 358 - 372
(2011/04/17)
-
- Enantioselective synthesis of anti -β-hydroxy-α-amido esters via transfer hydrogenation
-
The asymmetric transfer hydrogenation of α-amido-β-keto esters to provide the corresponding anti-β-hydroxy-α-amido esters in good to excellent yields, diastereoselectivity, and enantioselectivity is reported. The procedure is operationally simple, and delicate handling of the catalyst is not necessary.
- Seashore-Ludlow, Brinton,Villo, Piret,Haecker, Christine,Somfai, Peter
-
supporting information; experimental part
p. 5274 - 5277
(2011/01/12)
-
- Synthesis and electrochemical behaviour of β-halodehydroamino acid derivatives
-
Several new β,β-dihalo and β-halo-β-substituted dehydroalanines and dehydrodipeptides were synthesized by reacting the corresponding dehydroamino acid derivative with a N-halosuccinimide or in the case of β,β-di-iododehydroalanines with iodine. The results obtained confirmed that the stereochemical outcome of the halogenation reaction with β-substituted dehydroamino acids depends on the substrate. Thus, an increase Z-stereoselectivity was found when the β-phenyldehydroalanines were used as substrates and when these compounds were N-protected with 4-tolylsulfonyl or with carbamates. From this study, it is also possible to conclude that when N-iodosuccinimide was used as reagent a much higher Z-stereoselectivity is found. The electrochemical behaviour of the halogenated dehydroamino acids was studied by cyclic voltammetry. The results show a shift in the reduction peak to higher potentials of the β-halogenated dehydroamino acids when compared with the corresponding non-halogenated derivatives. As expected, the β,β-dihalodehydroalanines exhibit higher peak potentials than β-halo-β-substituted dehydroalanines and the bromo derivatives have lower peak potentials when compared with the corresponding iododehydroamino acids. Controlled potential electrolysis of several β-halo-β-substituted dehydroamino acids afforded the corresponding dehalogenated dehydroamino acids as mixtures of their E and Z-isomers. In all cases, the major isomer isolated results from dehalogenation without isomerization. These new results show that electrochemical reduction constitutes a valuable method for the synthesis of the E-isomer of β-substituted dehydroalanines. Springer-Verlag 2010.
- Ferreira, Paula M. T.,Monteiro,Pereira
-
experimental part
p. 499 - 513
(2010/11/04)
-
- PROCESS FOR PRODUCING OPTICALLY ACTIVE β-HYDROXY-α-AMINOCARBOXYLIC ACID DERIVATIVE
-
[PROBLEMS] To provide a process for efficiently producing the anti isomer of an optically active β-hydroxy-α-aminocarboxylic acid derivative useful as an intermediate for medicines/agricultural chemicals. [MEANS FOR SOLVING PROBLEMS] The process, which is for producing an optically active β-hydroxy-α-aminocarboxylic acid derivative represented by the formula (2) or (3) [Chemical formula 3] (wherein R1 means (un)substituted C1-20 alkyl or an (un)substituted C4-12 aromatic group and R2 means (un)substituted C1-20 alkyl or an (un)substituted C4-12 aromatic group), comprises hydrogenating an α-aminoacylacetic ester compound represented by the formula (1): [Chemical formula 1] [wherein R1 and R2 have the same meanings as defined above] in the presence of an acid through a catalytic asymmetric hydrogenation reaction employing as a catalyst a rhodium complex having as a ligand an optically active compound represented by the formula (4), (4'), or (5): [Chemical formula 2] the process being characterized in that the hydrogenation is conducted in the presence of an acetic acid salt.
- -
-
Page/Page column 24-25; 27
(2008/06/13)
-
- Expedient synthesis of threo-β-hydroxy-α-amino acid derivatives: Phenylalanine, tyrosine, histidine, and tryptophan
-
An expedient synthesis of enantiomerically pure threo-β-hydroxy- α-amino acid derivatives of phenylalanine, tyrosine, histidine, and tryptophan is described. The NBS-mediated radical bromination of the N,N-di-tert-butoxycarbonyl protected α-amino acids an
- Crich, David,Banerjee, Abhisek
-
p. 7106 - 7109
(2007/10/03)
-
- Stereoselective synthesis of β-hydroxyphenylalanines using imino 1,2-Wittig rearrangement of hydroximates
-
The imino 1,2-Wittig rearrangement of hydroximates containing a furan ring provides a novel method for the synthesis of β-hydroxy-α-amino acids. Upon treatment with LDA, hydroximates smoothly underwent the rearrangement to give Z-2-hydroxyoxime ethers in good yield, which were converted into both cis- and trans-oxazolidinones with high stereoselectivity. The cis- and trans-oxazolidinones were stereoselectively converted into erythro- and thereo-β-hydroxypheny lalanines, respectively, via the oxidative cleavage of a furan ring, ring-opening of oxazolidinone, and deprotection.
- Miyata, Okiko,Asai, Hiroshi,Naito, Takeaki
-
p. 355 - 360
(2007/10/03)
-
- Catalytic enantio- and diastereoselective aldol reactions of glycine-derived silicon enolate with aldehydes: An efficient approach to the asymmetric synthesis of anti-β-hydroxy-α-amino acid derivatives
-
We have developed an efficient method for the asymmetric synthesis of anti-β-hydroxy-α-amino acid derivatives based on highly enantio- and diastereoselective aldol reactions of the silicon enolate derived from N-trifluoroacetylglycinate with aldehydes using a chiral zirconium catalyst. The resulting N-trifluoroacetyl group is easily cleaved under either acidic or basic conditions and can be used directly as a protecting group for further transformations. Copyright
- Kobayashi, Jun,Nakamura, Masayuki,Mori, Yuichiro,Yamashita, Yasuhiro,Kobayashi, Shu
-
p. 9192 - 9193
(2007/10/03)
-
- A CD exciton chirality method for determination of the absolute configuration of threo-β-aryl-β-hydroxy-α-amino acid derivatives
-
The absolute configuration of threo-β-aryl-β-hydroxy-α-amino acids was studied by CD exciton chirality method using 7-diethylaminocoumarin-3-carboxylate as a red-shifted chromophore. Bischromophoric derivatives for a series of threo-β-aryl-β-hydroxy-α-amino acids (3a-h) were prepared and their CD spectra measured in CH2Cl2. By combining the data of CD and NMR coupling constants, we are able to correlate their preferred conformer (B) and the positive CD to the corresponding (2S,3R)-absolute configuration. These results are consistent with those obtained from serine and threonine derivatives, which represent the simplest form of β-hydroxy-α-amino acids. This CD method could thus become a general method for determining the absolute configuration of threo-β-aryl-β-hydroxy-α-amino acids.
- Lo, Lee-Chiang,Yang, Chun-Tzu,Tsai, Charng-Sheng
-
p. 1368 - 1371
(2007/10/03)
-