Catalytic Asymmetric Hydrogenation of Dehydroamino Acid Esters with Biscarbamate Protection and Its Application to the Synthesis of xCT Inhibitors

Yasuno, Yoko; Mizutani, Iho; Sueuchi, Yuki; Wakabayashi, Yuuka; Yasuo, Nozomi; Shimamoto, Keiko; Shinada, Tetsuro

doi:10.1002/chem.201900289

Cited by 5 publications

(4 citation statements)

References 51 publications

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“…We have reported the stereoselective synthesis of optically active N ‐benzoyl diaminosuberic acids (DAS) for the development of cystine‐glutamate exchanger (xCT) inhibitors (Scheme 4). [13] To this end, DuPHOS‐Rh‐catalyzed asymmetric reduction [14] was successfully applied to the stereoselective synthesis of four stereoisomers of 15 with different protecting groups on the amino groups. We expected that the same strategy would be applicable to the synthesis of 10 from 9 (Scheme 5).…”

Section: Resultsmentioning

confidence: 99%

“…[16] 4-((R,Z)-4-acetamido-1-((tert-butyldimethylsilyl)oxy)-5-methoxy-5-oxopent-3-en-1-yl)-2,2-dimethyloxazolidine-3-carboxylate (9). To a solution of 13 [11] 13 1746, 1690, 1649, 1541, 1388, 1254, 1220, 1161, 1073, 1021, 964, 938, 833, 777, 721, 686, 588, 555, 519. 1 -(5R,7)-dihydroxy-heptanoic acid (1).…”

Section: Tert-butyl (R)-4-((r)-1-((tert-butyldimethylsilyl)oxy)but-3-mentioning

confidence: 99%

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Stereoselective Synthesis of (2S,6R)‐Diamino‐(5R,7)‐dihydroxy‐heptanoic Acid (DADH): An Unusual Amino Acid from Streptomyces sp. SANK 60404

et al. 2021

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Stereoselective synthesis of (2S,6R)‐diamino‐(5R,7)‐dihydroxy‐heptanoic acid (DADH), a biosynthetic precursor of vazabitide A, isolated from Streptomyces sp. SANK 60404 was achieved for the first time. Three stereogenic centers of DADH were constructed by the chemical manipulation on Garner's aldehyde as a chiral source and DuPHOS‐Rh‐catalyzed asymmetric hydrogenation of a dehydroamino acid ester. The synthetic advantage of the present method was demonstrated by the flexible synthesis of the DADH stereoisomers from Garner's aldehyde.

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Section: Resultsmentioning

confidence: 99%

Section: Tert-butyl (R)-4-((r)-1-((tert-butyldimethylsilyl)oxy)but-3-mentioning

confidence: 99%

Stereoselective Synthesis of (2S,6R)‐Diamino‐(5R,7)‐dihydroxy‐heptanoic Acid (DADH): An Unusual Amino Acid from Streptomyces sp. SANK 60404

et al. 2021

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“…Among others, α-(dialkoxyphosphoryl)glycinates became the crucial synthetic tool commonly used for the synthesis of many natural products (including β-lactam antibiotics) or α,β-dehydro-α-amino acids by the Wadsworth-Emmons reaction [ 90 , 91 , 92 , 93 , 94 , 95 , 96 ]. As is known, hydrogenation of the latter compounds using chiral catalysts is considered to be one of the most general methods for the enantioselective synthesis of α-amino acids, including non-proteinogenic α-amino acids of diverse biological activities [ 97 , 98 , 99 , 100 ].…”

Section: 1-aminoalkyltriarylphosphonium Derivativesmentioning

confidence: 99%

1-Aminoalkylphosphonium Derivatives: Smart Synthetic Equivalents of N-Acyliminium-Type Cations, and Maybe Something More: A Review

et al. 2022

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N-acyliminium-type cations are examples of highly reactive intermediates that are willingly used in organic synthesis in intra- or intermolecular α-amidoalkylation reactions. They are usually generated in situ from their corresponding precursors in the presence of acidic catalysts (Brønsted or Lewis acids). In this context, 1-aminoalkyltriarylphosphonium derivatives deserve particular attention. The positively charged phosphonium moiety located in the immediate vicinity of the N-acyl group significantly facilitates Cα-P+ bond breaking, even without the use of catalyst. Moreover, minor structural modifications of 1-aminoalkyltriarylphosphonium derivatives make it possible to modulate their reactivity in a simple way. Therefore, these types of compounds can be considered as smart synthetic equivalents of N-acyliminium-type cations. This review intends to familiarize a wide audience with the unique properties of 1-aminoalkyltriarylphosphonium derivatives and encourage their wider use in organic synthesis. Hence, the most important methods for the preparation of 1-aminoalkyltriarylphosphonium salts, as well as the area of their potential synthetic utilization, are demonstrated. In particular, the structure–reactivity correlations for the phosphonium salts are discussed. It was shown that 1-aminoalkyltriarylphosphonium salts are not only an interesting alternative to other α-amidoalkylating agents but also can be used in such important transformations as the Wittig reaction or heterocyclizations. Finally, the prospects and limitations of their further applications in synthesis and medicinal chemistry were considered.

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“…Stereochemistry is an important factor in drug design because changes affect biological chemistry. , In rapadocins, differences in stereochemistry induced 200-fold changes in IC 50 (Figure S2). Furthermore, among diaminosuberic amino acid-derived compounds with two stereocenters yielding four stereoisomers, only a single stereoisomer among the four exhibited high inhibitory activity in the micromolar range against the amino acid transporter . Therefore, the diversification of stereochemistry is one of the important strategies for nature to generate natural products with a wide range of biological functions.…”

Section: Introductionmentioning

confidence: 99%

Mechanisms of Sugar Aminotransferase-like Enzymes to Synthesize Stereoisomers of Non-proteinogenic Amino Acids in Natural Product Biosynthesis

et al. 2023

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(2,6)-Diamino-(5,7)-dihydroxyheptanoic acid (DADH), a non-proteinogenic amino acid, is converted to 1-azabicyclo[3.1.0]hexane ring-containing amino acids that are subsequently incorporated into ficellomycin and vazabitide A. The present study revealed that the sugar aminotransferase-like enzymes Fic25 and Vzb9, with a high amino acid sequence identity (56%) to each other, synthesized stereoisomers of DADH with (6S) and (6R) configurations, respectively. The crystal structure of the Fic25 complex with a PLP-(6S)–N 2-acetyl-DADH adduct indicated that Asn45 and Gln197 (Asn205 and Ala53 in Vzb9) were located at positions that affected the stereochemistry of DADH being synthesized. A modeling study suggested that amino acid substitutions between Fic25 and Vzb9 allowed the enzymes to bind to the substrate with almost 180° rotation in the C5–C7 portions of the DADH molecules, accompanied by a concomitant shift in their C1–C4 portions. In support of this result, the replacement of two corresponding residues in Fic25 and Vzb9 increased (6R) and (6S) stereoselectivities, respectively. The different stereochemistry at C6 of DADH resulted in a different stereochemistry/orientation of the aziridine portion of the 1-azabicyclo[3.1.0]hexane ring, which plays a crucial role in biological activity, between ficellomycin and vazabitide A. A phylogenic analysis suggested that Fic25 and Vzb9 evolved from sugar aminotransferases to produce unusual building blocks for expanding the structural diversity of secondary metabolites.

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Catalytic Asymmetric Hydrogenation of Dehydroamino Acid Esters with Biscarbamate Protection and Its Application to the Synthesis of xCT Inhibitors

Abstract: Catalytic asymmetric hydrogenation of dehydroamino acid esters with biscarbamate protection was examined for the first time to prepare optically active amino acids. The new method was successfully applied to the synthesis of new cystine–glutamate exchanger inhibitors.

Cited by 5 publications

References 51 publications

Stereoselective Synthesis of (2S,6R)‐Diamino‐(5R,7)‐dihydroxy‐heptanoic Acid (DADH): An Unusual Amino Acid from Streptomyces sp. SANK 60404

Stereoselective Synthesis of (2S,6R)‐Diamino‐(5R,7)‐dihydroxy‐heptanoic Acid (DADH): An Unusual Amino Acid from Streptomyces sp. SANK 60404

1-Aminoalkylphosphonium Derivatives: Smart Synthetic Equivalents of N-Acyliminium-Type Cations, and Maybe Something More: A Review

Mechanisms of Sugar Aminotransferase-like Enzymes to Synthesize Stereoisomers of Non-proteinogenic Amino Acids in Natural Product Biosynthesis

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