Synthesis of secorapamycin esters and amides

Skotnicki, Jerauld S.; Kearney, Robert M.; Smith, Alastair

doi:10.1016/s0040-4039(00)76509-9

Cited by 18 publications

(8 citation statements)

References 12 publications

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“…However, the use of H 2 gas in the presence of Pd/C afforded the desired cis-alkene 18 . For the synthesis of trans-isomer, the authors utilized the already-established cis-compound as the reactant [ 56 , 57 ].…”

Section: Resultsmentioning

confidence: 99%

Design and Synthesis of Small Molecules as Potent Staphylococcus aureus Sortase A Inhibitors

Paek

2020

Antibiotics

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The widespread and uncontrollable emergence of antibiotic-resistant bacteria, especially methicillin-resistant Staphylococcus aureus, has promoted a wave of efforts to discover a new generation of antibiotics that prevent or treat bacterial infections neither as bactericides nor bacteriostats. Due to its crucial role in virulence and its nonessentiality in bacterial survival, sortase A has been considered as a great target for new antibiotics. Sortase A inhibitors have emerged as promising alternative antivirulence agents against bacteria. Herein, the structural and preparative aspects of some small synthetic organic compounds that block the pathogenic action of sortase A have been described.

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Section: Resultsmentioning

confidence: 99%

Design and Synthesis of Small Molecules as Potent Staphylococcus aureus Sortase A Inhibitors

Paek

2020

Antibiotics

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“…The compound 3 was coupled with commercially available trans -3-(thiophene-2-yl)acrylic acid ( 4a ) in the presence of ethyl( N,N -dimethylaminopropyl) carbodiimide (EDAC) and N,N -dimethylaminopyridine (DMAP) in 1,2-dichloroethane to form the amide compound 5a [31]. Basic hydrolysis of the ester methyl group present in compound 5a afforded the inhibitor 1 as a white crystalline solid.…”

Section: Resultsmentioning

confidence: 99%

Synthesis and structure activity relationship studies of novel Staphylococcus aureus Sortase A inhibitors

Chenna

King

Shinkre

et al. 2010

European Journal of Medicinal Chemistry

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Synthetic methods have been developed for the lead Sortase A inhibitors identified from previous studies. Several derivatives of the lead inhibitor were synthesized to derive preliminary structure activity relationships (SAR). Different regions of the lead inhibitor that are critical for the enzyme activity have been determined by systematic SAR studies. The E stereochemistry of the lead compound was found to be critical for its activity. Replacement of the E double bond with Z double bond or a rigid triple bond reduced the enzyme inhibitory activity in most cases. Reduction of the double bond to a C-C single bond resulted in complete loss of activity. Amide carbonyl and NH groups were also found to be crucial for the activity of this class of inhibitors, as well. Morpholine ring oxygen atom was also found to be important factor for the activity of the lead inhibitor. Preliminary SAR studies led to the identification of compounds with improved enzyme inhibition. The most active compound was found to have an IC50 value of 58εM against the enzyme.

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“…Corresponding S P -2-iodoferrocenecarboxylic acid (S P -7) 15 was synthesized from 3-O-(ferrocenecarbonyl)-1,2:5,6-di-O-isopropylidene-α-D-glucofuranose by (i) deprotonative metalation in THF using lithium (S)-bis(1-phenylethyl)amide (2 x 2 equiv at 10 min interval) through a double asymmetric induction process in the presence of ZnCl 2 •TMEDA (1 equiv) as in situ trap, followed by iodolysis as described previously, 16 and (ii) saponification of the ester. Both 2-substituted ferrocenecarboxamides rac-8 and S P -8 were synthesized in 84% yield, respectively from rac-7 and S P -7, by HOBt/EDCI-mediated peptidic coupling 12 using ethyl glycinate hydrochloride (H-Gly-OEt.HCl) as partner. Treatment with N-protected glycine Boc-Gly-OH in the presence of Cu 2 O at acetonitrile reflux 11 led to the substitution products rac-9 and S P -9 in 50% yield (Scheme 4).…”

Section: Methodsmentioning

confidence: 99%

“…Towards this purpose, aminoferrocene (1) was prepared by (i) deprotometalation of ferrocene 9 followed by iodolysis, 10 and (ii) treatment of the iodide with phthalimide in the presence of Cu 2 O in acetonitrile followed by deprotection. 11 Peptidic coupling was next performed in the presence of 1-hydroxybenzotriazole (HOBt) and 1-ethyl-3-(3dimethylaminopropyl)carbodiimide (EDCI) 12 from 1 by using N α -Boc-L-tryptophan (Boc-Trp-OH), the (N-protected) Sugar Amino Acids (SAA) N-Boc-3-amino-3-deoxy-1,2-Oisopropylidene-α-D-ribofuranoic acid (SAA-1) and N-Boc-3amino-3-deoxy-1,2-O-isopropylidene-α-D-xylofuranoic acid (SAA-2), as well as the corresponding homodimers (SAA-3 and SAA-4) and heterodimer (SAA-5) as partners, to afford the respective Ferrocene Carboxamides FcC-0 to FcC-5 in yields ranging from 60 to 66% (Table 1). Further, amine deprotection of FcC-0 by trifluoroacetic acid (TFA) and peptidic coupling with Boc-Trp-OH provided FcC-6 in 63% yield (Scheme 1).…”

Section: Synthesismentioning

confidence: 99%

Synthesis of ferrocene amides and esters from aminoferrocene and 2-substituted ferrocenecarboxylic acid and properties thereof

et al. 2016

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International audienceDifferent ferrocenecarboxamides were synthesized from aminoferrocene and various acid coupling partners such as N-alpha-Boc-L-tryptophan and N-protected sugar amino acids ( N-Boc-3-amino-3-deoxy-1,2-O-isopropylidene-alpha-D-ribofuranoic acid, N-Boc-3-amino-3-deoxy-1,2-O-isopropylidene-alpha-D-xylofuranoic acid and their corresponding homo- and hetero-dimers). Similarly, reactions between 2-aminoethyl ferrocenecarboxylate and N-protected sugar amino acids afforded compounds with a carboxamide functional group remotely positioned from the ferrocene core. The X-ray diffraction structure of one of them showed the presence of an intermolecular hydrogen bond between the amide functional groups. Carbonylamino ( or carbonyloxy) and oxycarbonyl 1,2-disubstituted ferrocenes were prepared either as racemic mixtures or in enantiomerically pure ( S-P) form. Their electrochemical evaluation revealed distinctive features. Interestingly, the enantiomerically pure ferrocene diester showed a large potential shift (+45 mV) in the presence of L-glutamic acid. Finally, some of the synthesized ferrocenes were evaluated for their antibacterial, antifungal and antiproliferative ( MCF-7) activities

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Synthesis of secorapamycin esters and amides

Cited by 18 publications

References 12 publications

Design and Synthesis of Small Molecules as Potent Staphylococcus aureus Sortase A Inhibitors

Design and Synthesis of Small Molecules as Potent Staphylococcus aureus Sortase A Inhibitors

Synthesis and structure activity relationship studies of novel Staphylococcus aureus Sortase A inhibitors

Synthesis of ferrocene amides and esters from aminoferrocene and 2-substituted ferrocenecarboxylic acid and properties thereof

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