Mannich-Type Reaction for Synthesis of 3-Methyl-4-nitroimino-tetrahydro-1,3,5-oxadiazine

Qu, Wen‐Yan; She, Dongmei; Zhao, Jian; Lin, De‐Jie; Huang, Qing‐An; Li, Fengmin

doi:10.1080/00397911.2010.550705

“…The stapling yield of 15 carrying 5 Ala dropped to 35 % under the same conditions. In comparison with 1, the corresponding cyclization of its structural analog 1' bearing 20). Circular dichroism (CD) analysis of representative stapled product 22 showed a significant increase of ahelicity (45 %) compared with the linear precursors, whereas 23 showed a negligible increase of a-helicity (14 %, see SI for details).…”

Section: Resultsmentioning

confidence: 99%

“…HCHO in HFIP in 2 hours. [20] Notably, intermediates such as 41 bearing a monomethylene linchpin were not detected by LC-MS analysis. Unlike the mono methylene linkage between Lys and Cys, the tetrahydrotriazine linkage is stable in aqueous solution of a wide range of pH (1-12) at rt (see SI Figures 33-35 for details).…”

Section: Resultsmentioning

confidence: 99%

Cooperative Stapling of Native Peptides at Lysine and Tyrosine or Arginine with Formaldehyde

Li

¹

,

Tang

²

,

Turlik

³

et al. 2021

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Stapling of peptides by intramolecular crosslinking of two neighboring amino acid side chains offers an important tool to modulate the structure and properties of peptides. In comparison to the stapling of artificially engineered peptide substrates, methods for stapling native peptides are more desirable for easier accessibility and genetic encodability. However, the existing strategy for selectivity control in the stapling of native peptides is relatively limited: the site of anchoring is often dominated by Cys, and the means for achieving the position selectivity among the same type of residues at different locations is lacking. We have developed a simple and powerful strategy for stapling native peptides at lysine residues with formaldehyde by the cooperation of nearby tyrosine or arginine residues. The stapling reactions can proceed with high efficiency and residue selectivity under mild conditions, and generate linchpins with distinct physiochemical properties. The new method for peptide stapling enables unique control of position‐selectivity for substrates bearing multiple reaction sites by reactivity that can be readily built in the peptide sequence.

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“…The mixture was heated at 90 • C for 6 h. Most of the compounds were obtained from moderate to good yields. The reaction proceeded through the Mannich-type reaction; here, the acid was used as a catalyst to promote the reaction where the key intermediate was the diol, which was then cyclized to obtain the corresponding cyclic nitroguanidine (Scheme 4) [16]. To obtain the N-methylated compounds 33−42, compound 32 was synthesized using phthaloyl chloride, pyridine, and a solution of HCl/H2O.…”

Section: Synthesismentioning

confidence: 99%

“…The addition of the amine and the addition of the methylamine were nucleophilic substitutions that took place at the sp 2 carbon. The reaction proceeded through the Mannich-type reaction; here, the acid was used as a catalyst to promote the reaction where the key intermediate was the diol, which was then cyclized to obtain the corresponding cyclic nitroguanidine (Scheme 4) [16]. The reaction proceeded through the Mannich-type reaction; here, the acid was used as a catalyst to promote the reaction where the key intermediate was the diol, which was then cyclized to obtain the corresponding cyclic nitroguanidine (Scheme 4) [16].…”

Section: Synthesismentioning

confidence: 99%

“…The reaction proceeded through the Mannich-type reaction; here, the acid was used as a catalyst to promote the reaction where the key intermediate was the diol, which was then cyclized to obtain the corresponding cyclic nitroguanidine (Scheme 4) [16]. The reaction proceeded through the Mannich-type reaction; here, the acid was used as a catalyst to promote the reaction where the key intermediate was the diol, which was then cyclized to obtain the corresponding cyclic nitroguanidine (Scheme 4) [16]. To obtain the N-methylated compounds 33−42, compound 32 was synthesized using phthaloyl chloride, pyridine, and a solution of HCl/H2O.…”

Section: Synthesismentioning

confidence: 99%

See 1 more Smart Citation

Synthesis and Insecticidal Evaluation of Chiral Neonicotinoids Analogs: The Laurel Wilt Case

Luna-Hernández

¹

,

Bonilla‐Landa

²

,

Reyes-Luna

³

et al. 2021

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Xyleborus sp beetles are types of ambrosia beetles invasive to the United States and recently also to Mexico. The beetle can carry a fungus responsible for the Laurel Wilt, a vascular lethal disease that can host over 300 tree species, including redbay and avocado. This problem has a great economic and environmental impact. Indeed, synthetic chemists have recently attempted to develop new neonicotinoids. This is also due to severe drug resistance to “classic” insecticides. In this research, a series of neonicotinoids analogs were synthesized, characterized, and evaluated against Xyleborus sp. Most of the target compounds showed good to excellent insecticidal activity. Generally, the cyclic compounds also showed better activity in comparison with open-chain compounds. Compounds R-13, 23, S-29, and 43 showed a mortality percent of up to 73% after 12 h of exposure. These results highlight the enantioenriched compounds with absolute R configuration. The docking results correlated with experimental data which showed both cation-π interactions in relation to the aromatic ring and hydrogen bonds between the search cavity 3C79 and the novel molecules. The results suggest that these sorts of interactions are responsible for high insecticidal activity.

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Cooperative Stapling of Native Peptides at Lysine and Tyrosine or Arginine with Formaldehyde

Ли

¹

,

Tang

²

,

Turlik

³

et al. 2021

View full text Add to dashboard Cite

Stapling of peptides by intramolecular crosslinking of two neighboring amino acid side chains offers an important tool to modulate the structure and properties of peptides. In comparison to the stapling of artificially engineered peptide substrates, methods for stapling native peptides are more desirable for easier accessibility and genetic encodability. However, the existing strategy for selectivity control in the stapling of native peptides is relatively limited: the site of anchoring is often dominated by Cys, and the means for achieving the position selectivity among the same type of residues at different locations is lacking. We have developed a simple and powerful strategy for stapling native peptides at lysine residues with formaldehyde by the cooperation of nearby tyrosine or arginine residues. The stapling reactions can proceed with high efficiency and residue selectivity under mild conditions, and generate linchpins with distinct physiochemical properties. The new method for peptide stapling enables unique control of position‐selectivity for substrates bearing multiple reaction sites by reactivity that can be readily built in the peptide sequence.

show abstract

Mannich-Type Reaction for Synthesis of 3-Methyl-4-nitroimino-tetrahydro-1,3,5-oxadiazine

Cited by 10 publications

References 13 publications

Cooperative Stapling of Native Peptides at Lysine and Tyrosine or Arginine with Formaldehyde

Cooperative Stapling of Native Peptides at Lysine and Tyrosine or Arginine with Formaldehyde

Synthesis and Insecticidal Evaluation of Chiral Neonicotinoids Analogs: The Laurel Wilt Case

Cooperative Stapling of Native Peptides at Lysine and Tyrosine or Arginine with Formaldehyde

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