Synthetic studies on thiostrepton family of peptide antibiotics: synthesis of the pentapeptide segment containing dihydroxyisoleucine, thiazoline and dehydroamino acid

Higashibayashi, Shuhei; Kohno, Mitsunori; Goto, Taiji; Suzuki, Kengo; Mori, Takeo; Hashimoto, Kimiko; Nakata, Masaya

doi:10.1016/j.tetlet.2004.03.099

Cited by 38 publications

(34 citation statements)

References 70 publications

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“…Their approach was based on formation of a substituted central 1-pyrroline 39 that underwent ring-expansion to form a piperidine ring 37 ( a series) that could be selectively oxidized for form the corresponding 2,3,4,5-tetrahydropyridine 38 ( b series) [162] (Scheme 12). In further reports they described the synthesis of other fragments [163,164] of b series thiopeptides and finally achieved the total synthesis of siomycin A [165,166]. …”

Section: Thiopeptidesmentioning

confidence: 99%

Thiopeptide Antibiotics: Retrospective and Recent Advances

2014

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Thiopeptides, or thiazolyl peptides, are a relatively new family of antibiotics that already counts with more than one hundred different entities. Although they are mainly isolated from soil bacteria, during the last decade, new members have been isolated from marine samples. Far from being limited to their innate antibacterial activity, thiopeptides have been found to possess a wide range of biological properties, including anticancer, antiplasmodial, immunosuppressive, etc. In spite of their ribosomal origin, these highly posttranslationally processed peptides have posed a fascinating synthetic challenge, prompting the development of various methodologies and strategies. Regardless of their limited solubility, intensive investigations are bringing thiopeptide derivatives closer to the clinic, where they are likely to show their veritable therapeutic potential.

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Section: Thiopeptidesmentioning

confidence: 99%

Thiopeptide Antibiotics: Retrospective and Recent Advances

2014

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“…The amino groups of L- and D-threonine were protected through treatment with di- tert -butyl dicarbonate in aqueous sodium bicarbonate to give 17a 37 and 17b 38, respectively, by means of slight modification of a literature procedure 39. Cyclization to β-lactones 18a 40 and 18b was accomplished through treatment of 17a and 17b , respectively, with benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (BOP reagent) by means of a literature procedure 26. Subsequent deprotection of the amino group with trifluoroacetic acid in presence of p -toluensulfonic acid, following the same synthetic protocol adopted for 4a , b , gave the tosylate salts (3 S ,4 R )- and (3 R ,4 S )-2-methyl-4-oxo-3-oxetanylammonium toluene-4-sulfonate ( 19a 41 and 19b ).…”

Section: Chemistrymentioning

confidence: 99%

Synthesis and Structure−Activity Relationships of N-(2-Oxo-3-oxetanyl)amides as N-Acylethanolamine-hydrolyzing Acid Amidase Inhibitors

et al. 2010

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The fatty acid ethanolamides (FAEs) are a family of bioactive lipid mediators that include the endogenous agonist of peroxisome proliferator-activated receptor-α, palmitoylethanolamide (PEA). FAEs are hydrolyzed intracellularly by either fatty acid amide hydrolase or N-acylethanolamine-hydrolyzing acid amidase (NAAA). Selective inhibition of NAAA by (S)-N-(2-oxo-3-oxetanyl)-3-phenylpropionamide [(S)-OOPP, 7a] prevents PEA degradation in mouse leukocytes and attenuates responses to proinflammatory stimuli. Starting from the structure of 7a a series of β-lactones was prepared and tested on recombinant rat NAAA to explore structure-activity relationships (SARs) for this class of inhibitors and improve their in vitro potency. Following the hypothesis that these compounds inhibit NAAA by acylation of the catalytic cysteine, we identified several requirements for recognition at the active site and obtained new potent inhibitors. In particular, (S)-N-(2-oxo-3-oxetanyl)biphenyl-4-carboxamide (7h) was more potent than 7a at inhibiting recombinant rat NAAA activity (7a, IC50 = 420 nM; 7h, IC50 = 115 nM) in vitro and at reducing carrageenan-induced leukocyte infiltration in vivo.

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“…The overall strategy used by Hashimoto, Nakata, and co-workers is similar to the route used by Nicolaou et al to thiostrepton in terms of the disconnections of the major building blocks, although they elected to form the right-side dihydroquinoline-containing macrocycle first. The route relies on earlier studies by the research group, [82,97,98,115,116] including their approach to the tetrahydropyridine (Scheme 21) and dihydroquinoline (Scheme 29) units discussed earlier. The starting point was the aminopiperidine 88 (Scheme 21), which was transesterified to provide the more labile Tmse esters on the two thiazole groups, and the oxazolidinone NH group N-protected.…”

Section: Siomycin Amentioning

confidence: 99%

“…Thereafter, removal of the Boc group, accompanied by desilylation of the dihydroquinoline 8-hydroxy group, was followed by incorporation of pentapeptide 160, [116] in which the hydroxymethylthioamide serves as the precursor to the thiazoline ring. Formation of the thiazoline by treatment with DAST was followed by removal of Teoc, acetonide, and Tmse protecting groups using zinc chloride, side-chain elongation with the dipeptide 151, and macrocyclization to give 161.…”

Section: Siomycin Amentioning

confidence: 99%

From Amino Acids to Heteroaromatics—Thiopeptide Antibiotics, Nature's Heterocyclic Peptides

2007

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Amino acids, the building blocks of proteins, also serve as precursors to a wide range of other naturally occurring substances including alkaloids, antibiotics, and, the subject of this Review, heterocyclic peptides. Simple alpha-amino acids are converted into complex arrays of heteroaromatic rings that display interesting and potent biological activity. The thiopeptide antibiotics, with their complex molecular architectures, are wonderful examples. In this Review we show how organic chemists have developed innovative methods for the synthesis of the heterocyclic ring systems, including routes inspired by the likely biosynthetic processes, and successfully assembled such building blocks into the final target molecule by application of orthogonal protecting groups and coupling methodologies.

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Synthetic studies on thiostrepton family of peptide antibiotics: synthesis of the pentapeptide segment containing dihydroxyisoleucine, thiazoline and dehydroamino acid

Cited by 38 publications

References 70 publications

Thiopeptide Antibiotics: Retrospective and Recent Advances

Thiopeptide Antibiotics: Retrospective and Recent Advances

Synthesis and Structure−Activity Relationships of N-(2-Oxo-3-oxetanyl)amides as N-Acylethanolamine-hydrolyzing Acid Amidase Inhibitors

From Amino Acids to Heteroaromatics—Thiopeptide Antibiotics, Nature's Heterocyclic Peptides

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