Reactions of .ALPHA.-amino acid derivatives with thionyl chloride. An application to a synthesis of 7.ALPHA.-methoxycephalosporins.

Saito, Tatsuhiro; Hiraoka, Tetsuo

doi:10.1248/cpb.25.784

Cited by 7 publications

(2 citation statements)

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“…The previously reported reaction between amines and sulfur diimides is one of transimidation with the equilibrium lying on the side of the less basic amine which, in the reaction above, would have led to 3a . (An S- aminosulfenimine structure has been reported as one of the many products formed in the reaction of amines with elemental sulfur 6 and also as a minor product in the reaction of a cephalosporin with thionyl chloride in base …”

Section: Resultsmentioning

confidence: 99%

S-Aminosulfeniminopenicillins: Multimode β-Lactamase Inhibitors and Template Structures for Penicillin-Based β-Lactamase Substrates as Prodrugs

et al. 1998

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A series of novel penicillins, bearing an S-aminosulfenimine (R′(R′′)NSNd) side chain at the 6-position, have been prepared by direct reaction of a penicillin ester with sulfur diimides. A set of these structures, with the thiazolidine-ring sulfur in the sulfide oxidation state, exhibited a pattern of reactivity not previously encountered in penicillin chemistry, viz., cleavage of the β-lactam ring resulted in a rapid intramolecular displacement of the S-amino moiety as R′(R′′)NH. This was found to be the exclusive reaction occurring consequent on cleavage of the β-lactam ring. The mechanism of this process was delineated in a detailed study in basic methanol. That a similar reactivity pattern held for a penicillin salt in aqueous solution was also verified. Thus the salt 5bm (R′ ) CH 3 , R′′ ) p-CH 3 C 6 H 4 SO 2 ) behaved as a moderate substrate for β-lactamase type I from Bacillus cereus (k cat /K m ) 6.26 × 10 5 M -1 min -1 ). On enzyme-catalyzed hydrolysis of this compound, displacement of N-methyl-p-toluenesulfonamide (R′(R′′)NH) was directly observed ( 1 H NMR) and found to occur faster than displacement of this group from (intact) 5bm in aqueous buffer, by a factor of at least 600. These findings identified the potential of the S-aminosulfeniminopenicillin structure type to be developed as β-lactamase substrates for use as site-specificrelease prodrugs. A degree of enzyme inhibition was also observed with this set of thiazolidinering-sulfide structures with the most potent inhibitor having the most nucleofugic S-amino moiety p-ClC 6 H 4 SO 2 N(CH 3 ), indicating that displacement of this group, at the enzyme active site, played a role in their mode of inhibition. Structures with the thiazolidine-ring sulfur in the sulfone oxidation state were considerably more potent as inhibitors, with the structure 5a 2 being the most active. As this compound bore the least nucleofugic S-amino moiety C 2 H 5 OC(O)NH, it indicated that the mode of inhibition of the sulfones was distinct from that of the thiazolidine-ring sulfides; it is probable that the sulfones reacted in a manner similar to that shown by sulbactam viz., rapid scission of the thiazolidine-sulfone ring after cleavage of the β-lactam ring. Synergy of action was observed with 5a 2 at high concentration (78 µg/mL) against Escherichia coli when combined 1:1 with penicillin G; no synergy was observed at low concentration (4 µg/mL) when combined with pipericillin, indicating poor permeation characteristics.

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Section: Resultsmentioning

confidence: 99%

S-Aminosulfeniminopenicillins: Multimode β-Lactamase Inhibitors and Template Structures for Penicillin-Based β-Lactamase Substrates as Prodrugs

et al. 1998

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“…4-((1,2,3,4,5,6,7,8-Heptathiazocan-8-yl)methyl)morpholine showed valuable fungistatic and fungicidal activity [5]. There is only one example of heterocyclic derivatives of heptasulfur imide; methyl 7-(1,2,3,4,5,6,7,8-heptathiazocan-8-yl)-3-methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate was obtained in low (8%) yield in the reaction of the corresponding heterocyclic amine and disulfur dichloride [6]. Herein, we report the synthesis of previously unknown 8-(pyrimidin-2-yl)-1,2,3,4, 5,6,7,8-heptathiazocane and study of conditions of its formation.…”

Section: Introductionmentioning

confidence: 99%

8-(Pyrimidin-2-yl)-1,2,3,4,5,6,7,8-heptathiazocane

Ogurtsov

Ракитин

2019

Molbank

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Heptasulfur imides substituted by hereterocycle may be of interest as biologically active compounds. In this communication, the reaction of pyrimidin-2-amine 1 with disulfur dichloride was carefully investigated to give 8-(pyrimidin-2-yl)-1,2,3,4,5,6,7,8-heptathiazocane in good yield. The structure of the newly synthesized compound was established by means of elemental analysis, high resolution mass-spectrometry, 1H, 13C NMR and IR spectroscopy and mass-spectrometry.

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Sulfenimines

Claus

1990

Sulfenic Acids and Derivatives (1990)

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Reactions of .ALPHA.-amino acid derivatives with thionyl chloride. An application to a synthesis of 7.ALPHA.-methoxycephalosporins.

Cited by 7 publications

References 0 publications

S-Aminosulfeniminopenicillins: Multimode β-Lactamase Inhibitors and Template Structures for Penicillin-Based β-Lactamase Substrates as Prodrugs

S-Aminosulfeniminopenicillins: Multimode β-Lactamase Inhibitors and Template Structures for Penicillin-Based β-Lactamase Substrates as Prodrugs

8-(Pyrimidin-2-yl)-1,2,3,4,5,6,7,8-heptathiazocane

Sulfenimines

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