- Synthesis of meta-Carboranyl-(S)-homocysteine Sulfoxide
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New (S)-homocysteine derivatives containing a meta-carborane fragment were synthesized. m-Carboranyl-(S)-homocysteine sulfoxide was obtained as a mixture of diastereoisomers. The reduction of the side-chain carboxy group of N-tert-butoxycarbonyl-(S)-aspartic acid α-tert-butyl ester with sodium tetrahydridoborate was not accompanied by racemization.
- Gruzdev,Ustinova,Levit,Ol’shevskaya,Krasnov
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Read Online
- Stereoselective Synthesis of Protected l - Allo -Enduracididine and l -Enduracididine via Asymmetric Nitroaldol Reaction
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The diastereoselecetive and scalable synthesis of cyclic guanidine-containing nonproteinoginic amino acids, enduracididines, has been achieved. Both diastereomers, l - allo -enduracididine and l -enduracididine, were prepared via catalyst-controlled asymmetric nitroaldol reaction with the aldehyde precursor derived from l -aspartic acid. The cyclic guanidine of di-Cbz-protected l - allo -enduracididine was fully protected with an allyl group to suppress nucleophilic side reactions. Introduced allyl group was efficiently removed via π-allylpalladium chemistry without attaching the Cbz group on the cyclic guanidine moiety.
- Doi, Takayuki,Ganesan, A.,Masuda, Yuichi,Ohsawa, Kosuke,Thomas, Carys,Tokunaga, Takuya,Zhao, Hongbin
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supporting information
p. 942 - 948
(2020/03/23)
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- Improved enantioselective gram scale synthesis route to N-Fmoc-protected monofluoroethylglycine
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Fluorine, as a substituent in amino acids, has found its way into peptide and protein engineering. The basis for the use of this valuable tool is the synthetic accessibility of various fluorinated amino acids as building blocks of peptides and proteins. In this context, we present a straightforward eight-step synthesis of N-Fmoc-L-monofluoroethylglycine (MfeGly) via homoserine (Hse) as intermediate and using various nucleophilic fluorination strategies.
- Leppkes, Jakob,Hohmann, Thomas,Koksch, Beate
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- Process for preparing deuterated desmosine and derivatives thereof
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There is provided a process for preparing a compound represented by the following general formula (1) or a salt thereof, which comprises exchanging one or more of an amino proton in a compound represented by the following general formula (2) or a salt thereof to deuterium, and after the exchanging, converting a deuterium-exchanged compound of the compound represented by the general formula (2) or a salt thereof into the compound represented by the general formula (1) or a salt thereof: wherein, in the general formula (1), one, or two or more of hydrogen atom may be substituted with their isotope; and in the general formula (2), each of R1 is independently hydrogen atom, tert-butyloxycarbonyl group or benzyloxycarbonyl group, and R2 is independently tert-butyl group, benzyl group, methyl group or ethyl group.
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Page/Page column 7; 9; 11
(2019/05/18)
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- COMPLEX
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PROBLEM TO BE SOLVED: To provide a substance that can be used in a simple quantitative method for desmosines. SOLUTION: In the complex of the present invention, desmosine is bound to a protein directly or via a linking group at the side chain terminal of the 4-position of the pyridine ring of desmosine. SELECTED DRAWING: None COPYRIGHT: (C)2020,JPOandINPIT
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Paragraph 0076-0078
(2019/11/03)
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- Palladium-Catalyzed Suzuki-Miyaura Reactions of Aspartic Acid Derived Phenyl Esters
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Transition-metal-catalyzed transformations of amino acids and peptides could provide a powerful method for their site-selective modification. Here, we report non-decarbonylative Pd-catalyzed Suzuki-Miyaura reactions of phenyl ester derivatives of aspartic acid to form aryl-amino ketones. These products are potentially important in the synthesis of pharmaceuticals, and our methodology represents a new route to access molecules of this type.
- Dardir, Amira H.,Hazari, Nilay,Miller, Scott J.,Shugrue, Christopher R.
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supporting information
p. 5762 - 5766
(2019/08/01)
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- Multigram-scale and column chromatography-free synthesis of L-azetidine-2-carboxylic acid for the synthesis of nicotianamine and its derivatives
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Multigram-scale synthesis of L-azetidine-2-carboxylic acid from L-aspartic acid was achieved in 13 conventional synthetic steps, without the need for purification by silica-gel column chromatography and expensive reagents. Nicotianamine and its fluorescence-labeled derivatives could be obtained from this synthetic strategy.
- Takaishi, Tomohiro,Wakisaka, Kyosuke,Vavricka, Christopher J.,Kiyota, Hiromasa,Izumi, Minoru
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p. 2126 - 2134
(2019/04/04)
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- Synthesis of desmosine-d4: Improvement of isotopic purity by D-H exchange of amino groups
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Desmosine is a crosslinking pyridinium amino acid of elastin, which is a useful biomarker for the diagnosis of chronic obstructive pulmonary disease (COPD) by LC–MS/MS analysis. We previously reported a synthesis of desmosine-d4, which is useful as an internal standard for quantitative LC–MS/MS analysis of desmosines, by deuterogenation of an alkyne group; however, the isotopic purity of the desmosine-d4was only ca. 50%. The present report describes a new synthesis of desmosine-d4that improves the isotopic purity to ca. 90% by exchanging the protons of the amino groups to deuterium using deuterogenation.
- Watanabe, Daisuke,Suzuki, Rina,Usuki, Toyonobu
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supporting information
p. 1194 - 1197
(2017/03/02)
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- Synthesis of ortho-carboranyl derivatives of (S)-asparagine and (S)-glutamine
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(S)-Asparagine and (S)-glutamine ortho-carboranyl derivatives with free amino and carboxy groups in the α-position were synthesized. By an example of Nγ-(1,2-dicarba-closo-dodecarboran-3-yl)-(S)-glutamine it was demonstrated that the developed synthetic approach carboranyl derivatives of amino acids allowed the preparation of optically pure isomers.
- Gruzdev,Levit,Olshevskaya,Krasnov
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p. 769 - 776
(2017/07/07)
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- [18F](2S,4S)-4-(3-Fluoropropyl)glutamine as a tumor imaging agent
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Although the growth and proliferation of most tumors is fueled by glucose, some tumors are more likely to metabolize glutamine. In particular, tumor cells with the upregulated c-Myc gene are generally reprogrammed to utilize glutamine. We have developed new 3-fluoropropyl analogs of glutamine, namely [18F](2S,4R)- and [18F](2S,4S)-4-(3-fluoropropyl)glutamine, 3 and 4, to be used as probes for studying glutamine metabolism in these tumor cells. Optically pure isomers labeled with 18F and 19F (2S,4S) and (2S,4R)-4-(3-fluoropropyl)glutamine were synthesized via different routes and isolated in high radiochemical purity (>95%). Cell uptake studies of both isomers showed that they were taken up efficiently by 9L tumor cells with a steady increase over a time frame of 120 min. At 120 min, their uptake was approximately two times higher than that of L-[3H]glutamine ([3H]Gln). These in vitro cell uptake studies suggested that the new probes are potential tumor imaging agents. Yet, the lower chemical yield of the precursor for 3, as well as the low radiochemical yield for 3, limits the availability of [18F](2S,4R)-4-(3-fluoropropyl)glutamine, 3. We, therefore, focused on [18F](2S,4S)-4-(3-fluoropropyl)glutamine, 4. The in vitro cell uptake studies suggested that the new probe, [18F](2S,4S)-4-(3-fluoropropyl)glutamine, 4, is most sensitive to the LAT transport system, followed by System N and ASC transporters. A dualisotope experiment using L-[3H]glutamine and the new probe showed that the uptake of [3H]Gln into 9L cells was highly associated with macromolecules (>90%), whereas the [18F](2S,4S)-4-(3-fluoropropyl)glutamine, 4, was not (18F](2S,4S)-4-(3-fluoropropyl)glutamine, 4, may be useful for testing tumors that may metabolize glutamine related amino acids.
- Wu, Zehui,Zha, Zhihao,Li, Genxun,Lieberman, Brian P.,Choi, Seok Rye,Ploessl, Karl,Kung, Hank F.
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p. 3852 - 3866
(2016/10/13)
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- SINGLE DIASTEREOMERS OF 4-FLUOROGLUTAMINE AND METHODS FO THEIR PREPARATION AND USE
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The present invention is directed single diasteromers of 4-fluoroglutamine having a diastereomeric excess of at least 80%. Methods of preparing the single diastereomers are also described, as well as methods of using the single diastereomers of radiolabeled 4-fluoroglutamine as imaging agent is also described.
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Page/Page column 23
(2011/02/24)
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- Synthesis of optically pure 4-fluoro-glutamines as potential metabolic imaging agents for tumors
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A versatile synthetic route to prepare all four stereoisomeric 4-fluoro-glutamines was developed by exploiting a Passerini three-component reaction. The skeleton of 4-substituted glutamine derivatives was efficiently constructed. Subsequent four-step reactions, highlighted by a "neutralized" TASF fluorination, provided the desired products with high yields and excellent optical purity. The optically pure fluorine-18 labeled 4-fluoroglutamines were also successfully prepared using either a 18-crown-6/KHCO3 or K[222]/K2CO3 catalysis system. Preliminary cell uptake and inhibition studies using the 9L tumor cells ana SF188BC1-XL tumor cells (a glutamine addicted tumor derived from glioblastoma) provided strong evidence for their potential application in conjunction with positron emission tomography (PET) for in vivo imaging of tumors, which use glutamine as an alternative energy source.
- Qu, Wenchao,Zha, Zhihao,Ploessl, Karl,Lieberman, Brian P.,Zhu, Lin,Wise, David R.,Thompson, Craig B.,Kung, Hank F.
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supporting information; experimental part
p. 1122 - 1133
(2011/04/16)
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- Utility of tetrathiomolybdate and tetraselenotungstate: Efficient synthesis of cystine, selenocystine, and their higher homologues
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Efficient synthesis of cystine, selenocystine, and their higher homologues like homo and bishomo amino acid derivatives from natural amino acid derivatives using tetrathiomolybdate and tetraselenotungstate reagents under mild and neutral conditions is reported. The generality of the reaction has been studied by capping various groups to amino and carboxyl components of canonical amino acids.
- Bhat, Ramakrishna G.,Porhiel, Emmanuel,Saravanan, Vadivelu,Chandrasekaran, Srinivasan
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p. 5251 - 5253
(2007/10/03)
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- The synthesis of pyrimidin-4-yI substituted a-amino acids. a versatile approach from alkynyl ketones
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The reaction of amidines with a-amino acid alkynyl ketones is shown to be a versatile route to pyrimidin-4-yl substituted a-amino acids. This route is also applicable to a parallel synthesis approach and has allowed the formation of a range of pyrimidin-4-yl substituted a-amino acids, including the naturally occurring a-amino acid L-lathyrine 4.
- Adlington, Robert M.,Baldwin, Jack E.,Catterick, David,Pritchard, Garcth J.
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p. 855 - 866
(2007/10/03)
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- Chirospecific Synthesis of (1S,3R)-1-Amino-3-(hydroxymethyl)cyclopentane, Precursor for Carbocyclic Nucleoside Synthesis. Dieckmann Cyclization with an α-Amino Acid
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Carbocyclic nucleosides are important isosters of nucleosides possessing a variety of antiviral and antineoplastic activities.We report here a new method for the chirospecific synthesis of (1S,3R)-1-amino-3-(hydroxymethyl)cyclopentane.This compound is a key precursor for the synthesis of some carbocyclic nucleosides.The method involves (1) an improved synthesis of (S)-2-aminoadipic acid; (2) Dieckmann cyclization of this α-amino acid to an aminocyclopentanone; and (3) elaboration of the latter to the target (1S,3R)-1-amino-3-(hydroxymethyl)cyclopentane.The starting (S)-2-aminoadipic acid δ-methyl ester was prepared enantiomerically pure from (S)-aspartic acid in 51percent overall yield.Dieckmann condensation converted this amino acid to a (methoxycarbonyl)-cyclopentanone, and reduction of the ketone followed by elimination yielded (S)-3--1-(methoxycarbonyl)cyclopentene.Reduction of the double bond gave a mixture of the cis and trans diastereomers.This mixture was converted to a single diastereomer by epimerization and trapping of the cis isomer as (1S,4R)-2-(9-phenylfluoren-9-yl)-2-azabicycloheptan-3-one.Hydrolytic cleavage of the lactam followed by reduction gave (1S,3R)-1-amino-3-(hydroxymethyl)cyclopentane.
- Bergmeier, Stephen C.,Cobas, Agustin A.,Rapoport, Henry
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p. 2369 - 2376
(2007/10/02)
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- Synthesis of Stereospecific Deuterium-Labeled Homoserines and Homoserine Lactones
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The syntheses of the stereospecific deuteriated derivatives (2S,4R)- and (2S,4S)-2H>homoserine lactone hydrochlorides, (2S,3R)-2H>- and (2S,3S)-2H2>homoserine lactone hydrochlorides, and (2S,3R,4R)-2H2>- and (2S,3S,4S)-2H3>homoserine lactone hydrochlorides as well as the homoserine derivatives themselves have been synthesized in eight simple steps from the appropriate aspartic acids via a route designed for maximal synthetic versatility.The enantiomeric excesses at carbon 4 of the deuteriated homoserines are R = 78percent (98percent 2H) and S = 82percent (98percent 2H) and at carbon 3 R = 100percent (98percent 2H2) and S = 100percent (95percent2H).
- Ramalingam, Kondareddiar,Woodard, Ronald W.
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p. 1900 - 1903
(2007/10/02)
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