Synthesis of carumonam (AMA-1080) and a related compound starting from (2R,3R)-epoxysuccinic acid.

Sendai, Michiyuki; Hashiguchi, Shohei; Tomimoto, Mitsumi; Kishimoto, Shinji; Matsuo, Taisuke; Ochiai, Masahito

doi:10.1248/cpb.33.3798

Cited by 20 publications

(8 citation statements)

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“…The new positions of two resonances, assigned as CH α and CH β of β-hydroxy-Asn-16 (equivalent to Asn-803 of HIF-1α), are indicated by arrows. study) and erythro, 3.0 Hz [23] ; for protected β-hydroxyaspartic acid, threo, 2.0 Hz, erythro, 4.0 Hz [27] ; and for protected β-hydroxyasparagine, threo 1.8-2.2 Hz [28].…”

Section: Figure 2 Amino Acid α-Proton Region Of the 2d 1 H-13 C Hsqc mentioning

confidence: 94%

“…Racemic threo-β-hydroxy-asparagine (44 % overall yield) was synthesized in in two steps from racemic threo-β-hydroxyaspartic acid by selective methyl esterification of the side chain carboxylic acid function [SOCl # (1 mol), excess methanol at 0 mC for 15 min then 20 mC for 90 min] as described above [22]. The monoester was then converted to the desired racemic threo-β-hydroxyasparagine via treatment with 25 % aqueous ammonia following the procedure of Sendai et al [23], as reported for the erythro isomer of threo-β-hydroxy--asparagine. Evaporation in acuo followed by washing of the resultant solid with water and recrystallization from aqueous ethanol gave a purified product ( 95 % by "H-NMR analysis).…”

Section: Methodsmentioning

confidence: 99%

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Hypoxia-inducible factor asparaginyl hydroxylase (FIH-1) catalyses hydroxylation at the β-carbon of asparagine-803

McNeill

Hewitson

Claridge

et al. 2002

Biochemical Journal

202

155

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Asparagine-803 in the C-terminal transactivation domain of human hypoxia-inducible factor (HIF)-1 alpha-subunit is hydroxylated by factor inhibiting HIF-1 (FIH-1) under normoxic conditions causing abrogation of the HIF-1alpha/p300 interaction. NMR and other analyses of a hydroxylated HIF fragment produced in vitro demonstrate that hydroxylation occurs at the beta-carbon of Asn-803 and imply production of the threo -isomer, in contrast with other known aspartic acid/asparagine hydroxylases that produce the erythro -isomer.

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Section: Figure 2 Amino Acid α-Proton Region Of the 2d 1 H-13 C Hsqc mentioning

confidence: 94%

Section: Methodsmentioning

confidence: 99%

Hypoxia-inducible factor asparaginyl hydroxylase (FIH-1) catalyses hydroxylation at the β-carbon of asparagine-803

McNeill

Hewitson

Claridge

et al. 2002

Biochemical Journal

202

155

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“…Further support for this proposal was provided by an extensive analysis of the 1D and 2D NMR data. Finally, hydrolysis of 2 with 6 N HCl, derivatization with Marfey’s reagent, HPLC-MS analysis, and comparison with the four synthetic stereoisomers of 3-hydroxyaspartic acid confirmed the presence of (2 R ,3 S )-3-hydroxyaspartic acid in pipecolidepsin B.…”

mentioning

confidence: 86%

Isolation and Structures of Pipecolidepsins A and B, Cytotoxic Cyclic Depsipeptides from the Madagascan Sponge Homophymia lamellosa

et al. 2014

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Two new cyclic depsipeptides, pipecolidepsins A and B (1 and 2), have been isolated from the sponge Homophymia lamellosa collected off the coast of Madagascar. Their structures were determined by a combination of NMR experiments and by LC-MS analysis of the amino acid fragments obtained by hydrolysis and derivatization using Marfey's reagent. In addition to several common amino acids, these peptides contain unusual residues, including 2-amino-3-hydroxy-4,5-dimethylhexanoic acid, 3-ethoxyasparagine, 3,4-dimethylglutamine, 4,7-diamino-2,3-dihydroxy-7-oxoheptanoic acid, and 3-hydroxyaspartic acid as well as a terminal 3-hydroxy-2,4,6-trimethylheptanoic acid residue. Pipecolidepsins A and B displayed cytotoxic activity against a panel of different human tumor cell lines.

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“…2E depicts the synthetic route to GB1 (1a). The synthesis of acid 4 was adopted from published procedures (20). The (2R,3R)epoxysuccinic acid (10) was converted to erythro-N(α)-methyl-3-hydroxy-L-aspartic acid (11) by treatment with methylamine−water under reflux.…”

Section: Pharmacologymentioning

confidence: 99%

Gatorbulin-1, a distinct cyclodepsipeptide chemotype, targets a seventh tubulin pharmacological site

Matthew

Chen

Ratnayake

et al. 2021

Proc. Natl. Acad. Sci. U.S.A.

128

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Tubulin-targeted chemotherapy has proven to be a successful and wide spectrum strategy against solid and liquid malignancies. Therefore, new ways to modulate this essential protein could lead to new antitumoral pharmacological approaches. Currently known tubulin agents bind to six distinct sites at α/β-tubulin either promoting microtubule stabilization or depolymerization. We have discovered a seventh binding site at the tubulin intradimer interface where a novel microtubule-destabilizing cyclodepsipeptide, termed gatorbulin-1 (GB1), binds. GB1 has a unique chemotype produced by a marine cyanobacterium. We have elucidated this dual, chemical and mechanistic, novelty through multidimensional characterization, starting with bioactivity-guided natural product isolation and multinuclei NMR-based structure determination, revealing the modified pentapeptide with a functionally critical hydroxamate group; and validation by total synthesis. We have investigated the pharmacology using isogenic cancer cell screening, cellular profiling, and complementary phenotypic assays, and unveiled the underlying molecular mechanism by in vitro biochemical studies and high-resolution structural determination of the α/β-tubulin−GB1 complex.

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Synthesis of carumonam (AMA-1080) and a related compound starting from (2R,3R)-epoxysuccinic acid.

Cited by 20 publications

References 0 publications

Hypoxia-inducible factor asparaginyl hydroxylase (FIH-1) catalyses hydroxylation at the β-carbon of asparagine-803

Hypoxia-inducible factor asparaginyl hydroxylase (FIH-1) catalyses hydroxylation at the β-carbon of asparagine-803

Isolation and Structures of Pipecolidepsins A and B, Cytotoxic Cyclic Depsipeptides from the Madagascan Sponge Homophymia lamellosa

Gatorbulin-1, a distinct cyclodepsipeptide chemotype, targets a seventh tubulin pharmacological site

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