Efficient Synthesis of Sivelestat Sodium Hydrate

Bijukumar, Gopinathenpillai; Maloyesh, Biswas; Sampat, S. S.; Bhirud, S. B.; Rajendra, Agarwal

doi:10.1080/00397910801982373

Cited by 5 publications

(5 citation statements)

References 1 publication

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“…The combined isolated yield of 7 was 76% (26.46 g, 95.6 mmol). The spectroscopic data of 7 matches that of the literature and commercial compound …”

Section: Experimental Sectionsupporting

confidence: 78%

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Leveraging a “Catch–Release” Logic Gate Process for the Synthesis and Nonchromatographic Purification of Thioether- or Amine-Bridged Macrocyclic Peptides

et al. 2018

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Macrocyclic peptides containing N-alkylated amino acids have emerged as a promising therapeutic modality, capable of modulating protein-protein interactions and an intracellular delivery of hydrophilic payloads. While multichannel automated solid-phase peptide synthesis (SPPS) is a practical approach for peptide synthesis, the requirement for slow and inefficient chromatographic purification of the product peptides is a significant limitation to exploring these novel compounds. Herein, we invent a "catch-release" strategy for the nonchromatographic purification of macrocyclic peptides. A traceless catch process is enabled by the invention of a dual-functionalized N-terminal acetate analogue, which serves as a handle for capture onto a purification resin and as a leaving group for macrocyclization. Displacement by a C-terminal nucleophilic side chain thus releases the desired macrocycle from the purification resin. By design, this catch/release process is a logic test for the presence of the key components required for cyclization, thus removing impurities which lack the required functionality, such as common classes of peptide impurities, including hydrolysis fragments and truncated sequences. The method was shown to be highly effective with three libraries of macrocyclic peptides, containing macrocycles of 5-20 amino acids, with either thioether- or amine-based macrocyclic linkages; in this latter class, the reported method represents an enabling technology. In all cases, the catch-release protocol afforded significant enrichment of the target peptides purity, in many cases completely obviating the need for chromatography. Importantly, we have adapted this process for automation on a standard multichannel peptide synthesizer, achieving an efficient and completely integrated synthesis and purification platform for the preparation of these important molecules.

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“…The combined isolated yield of 7 was 76% (26.46 g, 95.6 mmol). The spectroscopic data of 7 matches that of the literature and commercial compound …”

Section: Experimental Sectionsupporting

confidence: 78%

“…The spectroscopic data of 7 matches that of the literature and commercial compound. 42 1 H NMR (500 MHz, CDCl 3 ): δ 8.09 (d, J = 8.7 Hz, 2H), 7.37 (d, J = 8.7 Hz, 2H), 1.41 (s, 9H) ppm.…”

Section: Synthesis Of 2-(((4-(3-azidopropoxy)phenyl)sulfonyl)oxy)acet...mentioning

confidence: 99%

Leveraging a “Catch–Release” Logic Gate Process for the Synthesis and Nonchromatographic Purification of Thioether- or Amine-Bridged Macrocyclic Peptides

et al. 2018

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“…Particularly, compound 6 synthesized easier than sivelestat. 26 In summary, compound 6 has the potential to reduce ALI and associated inflammatory disorders, and may be approved as a candidate for the development of new agents in the treatment of neutrophilic inflammatory diseases.…”

Section: Resultsmentioning

confidence: 99%

Synthesis and pharmacological characterization of 2-aminobenzaldehyde oxime analogs as dual inhibitors of neutrophil elastase and proteinase 3

Hwang¹,

Wang²,

Wang³

et al. 2015

Bioorganic & Medicinal Chemistry

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“…These reported methods as depicted in Scheme also employed chiral chromatographic techniques, which are not feasible on industrial scale. In recent years, extensive efforts have been made towards the development of efficient synthetic methods for 1 ; few of them are superior, improved, and scalable over the first-generation syntheses …”

Section: Introductionmentioning

confidence: 99%

Industrial Application of the Forster Reaction: Novel One-Pot Synthesis of Cinacalcet Hydrochloride, a Calcimimetic Agent

Shinde

Niphade

Deshmukh

et al. 2011

Org. Process Res. Dev.

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Described is a new, practical, and one-pot process, based on the Forster reaction, for the synthesis of cinacalcet hydrochloride (1), a calcimimetic agent and calcium-sensing receptor antagonist. The synthesis comprises the condensation of (1R)-(+)-1-naphthylethyl amine (2) with benzaldehyde (3) followed by reaction of obtained Schiff’s base 4 with 1-(3-halopropyl)-3-(trifluoromethyl)benzene (5) to provide highly unstable iminium salt 6. Subsequent hydrolysis of 6 with water in the same pot yielded cinacalcet. The treatment of cinacalcet with hydrochloric acid during the workup process furnished 1 with an overall yield of around 60%. Our synthetic approach for 1, discussed in this report demonstrates industrial application of the century-old, unexplored name reaction, “Forster’s Reaction” or Forster−Decker synthesis.

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Efficient Synthesis of Sivelestat Sodium Hydrate

Cited by 5 publications

References 1 publication

Leveraging a “Catch–Release” Logic Gate Process for the Synthesis and Nonchromatographic Purification of Thioether- or Amine-Bridged Macrocyclic Peptides

Leveraging a “Catch–Release” Logic Gate Process for the Synthesis and Nonchromatographic Purification of Thioether- or Amine-Bridged Macrocyclic Peptides

Synthesis and pharmacological characterization of 2-aminobenzaldehyde oxime analogs as dual inhibitors of neutrophil elastase and proteinase 3

Industrial Application of the Forster Reaction: Novel One-Pot Synthesis of Cinacalcet Hydrochloride, a Calcimimetic Agent

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