- Progress towards the synthesis of piperazimycin A: synthesis of the non-proteogenic amino acids and elaboration into dipeptides
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This Letter describes the synthesis of the five non-proteogenic amino acids required for the total synthesis of piperazimycin A, and synthetic elaboration into multiple dipeptides. Importantly, this Letter details the first example of an elusive piperazic acid-piperazic acid coupling to form this key C5-C14 dipeptide.
- Phillip Kennedy,Lindsley, Craig W.
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scheme or table
p. 2493 - 2496
(2010/06/14)
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- Synthesis, radiolabeling, and biological evaluation of (R)- and (S)-2-amino-3-[18F]fluoro-2-methylpropanoic acid (FAMP) and (R)- and (S)-3-[18F]fluoro-2-methyl-2-n-(methylamino)propanoic acid (NMeFAMP) as potential PET radioligands for imaging brain tumors
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The non-natural amino acids (R)- and (S)-2-amino-3-fluoro-2-methylpropanoic acid 5 and (R)- and (S)-3-fluoro-2-methyl-2-N-(methylamino)propanoic acid 8 were synthesized in shorter reaction sequences than in the original report starting from enantiomerically pure (S)- and (R)-R-methyl-serine, respectively. The reaction sequence provided the cyclic sulfamidate precursors for radiosynthesis of (R)- and (S)-[18F]5 and (R)- and (S)-[ 18F]8 in fewer steps than in the original report. (R)- and (S)-[ 18F]5 and(R)-and (S)-[18F]8 were synthesized by no-carrier-added nucleophilic [18F]fluorination in 52-66% decay - corrected yields with radiochemical purity over 99%. The cell assays showed that all four compounds were substrates for amino acid transport and enter 9L rat gliosarcoma cells in vitro at least in part by system A amino acid transport. The biodistribution studies demonstrated that in vivo tumor to normal brain ratios for all compounds were high with ratios of 20:1 to115:1 in rats with intracranial 9L tumors. The (R)-enantiomers of [18F]5 and [ 18F]8 demonstrated higher tumor uptake in vivo compared to the (S)-enantiomers. 2009 American Chemical Society.
- Yu, Weiping,McConathy, Jonathan,Williams, Larry,Camp, Vernon M.,Malveaux, Eugene J.,Zhang, Zhaobin,Olson, Jeffrey J.,Goodman, Mark M.
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experimental part
p. 876 - 886
(2010/07/05)
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- Non-natural amino acids as modulating agents of the conformational space of model glycopeptides
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The synthesis and conformational analysis in aqueous solution of different α-methyl-α-amino acid di-amides, derived from serine, threonine, β-hydroxycyclobutane-α-amino acids, and their corresponding model β-O-glucopeptides, are reported. The study reveals that the presence of an α-methyl group forces the model peptides to adopt helix-like conformations. These folded conformations are especially significant for cyclobutane derivatives. Interestingly, this feature was also observed in the corresponding model glucopeptides, thus indicating that the α-methyl group and not the β-O-glucosylation process largely determines the conformational preference of the backbone in these structures. On the other hand, atypical conformations of the glycosidic linkage were experimentally determined. Therefore, when a methyl group was located at the Cβ atom with an R configuration, the glycosidic linkage was rather rigid. Never-theless, when the S configuration was displayed, a significant degree of flexibility was observed for the glycosidic linkage, thus showing both alternate and eclipsed conformations of the ψb dihedral angle. In addition, some derivatives exhibited an unusual value for the Φ2 angle, which was far from a value of -60° expected for a conventional β-O-glycosidic linkage. In this sense, the different conformations exhibited by these molecules could be a useful tool in obtaining systems with conformational preferences "a la carte".
- Fernandez-Tejada, Alberto,Corzana, Francisco,Busto, Jesus H.,Jimenez-Oses, Gonzalo,Peregrina, Jesus M.,Avenoza, Alberto
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supporting information; experimental part
p. 7042 - 7058
(2009/07/25)
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- Facile stereospecific synthesis and biological evaluation of (S)- and (R)-2-amino-2-methyl-4-[123I]iodo-3-(E)-butenoic acid for brain tumor imaging with single photon emission computerized tomography
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Both enantiomers of 2-amino-2-methyl-4-iodo-3-(E)-butenoic acid (IVAIB, 5) were radioiodoinated in 65-72% yield. (S)-IVAIB entered 9L gliosarcoma cells primarily via A-type transport in vitro with higher uptake than (R)-IVAIB. Biodistribution studies in rats with 9L gliosarcoma brain tumors demonstrated higher tumor to brain ratios with (S)-IVAIB (75:1 at 1 h) than (R)-IVAIB (7.7:1). In this model, (S)-IVAIB is superior to (R)-IVAIB and is a promising radiotracer for brain tumor imaging.
- Yu, Weiping,McConathy, Jonathan,Olson, Jeffrey,Camp, Vernon M.,Goodman, Mark M.
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p. 6718 - 6721
(2008/09/17)
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- Synthesis of (S)-N-tert-butoxycarbonyl-N,O-isopropylidene-α- methylserinal: A potential building block for the asymmetric synthesis of non-natural amino acids
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The title compound (S)-α-methylserinal acetonide has been efficiently prepared from (S)-α-methylserine, which is readily available in enantiomerically pure form by Curtius rearrangement of α,α-dialkyl 2- cyanoesters obtained by diastereoselective alkylation of (1S,2R,4R)-10- dicyclohexylsulfamoylisobornyl 2-cyanopropanoate using methoxymethyl iodide or paraformaldehyde as electrophiles by an extension of our recently developed methodology for the synthesis of α,α-dialkylamino acids.
- Alias, Myriam,Cativiela, Carlos,Diaz-De-Villegas, Maria D.,Galvez, Jose A.,Lapena, Yolanda
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p. 14963 - 14974
(2007/10/03)
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