Synthesis of new penem dithiocarbamates

Altamura, Maria Maddalena; Giannotti, Danilo; Perrotta, Enzo; Sbraci, Piero; Pestellini, V.; Arcamone, Federico; Satta, G.

doi:10.1016/s0960-894x(01)80918-5

Cited by 13 publications

(3 citation statements)

References 14 publications

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“…The dithiocarbamates from heterocyclic secondary amines ( I ), − analogues of piperidine, were considered to constitute an independent series because of their high reactivity, although no mechanism was proposed to explain their behavior …”

Section: Introductionmentioning

confidence: 99%

“…The dithiocarbamates from heterocyclic secondary amines (I), [17][18][19][20][21] analogues of piperidine, were considered to constitute an independent series because of their high reactivity, although no mechanism was proposed to explain their behavior. 12 This work aims to answer relevant questions about the reactivity of the dithiocarbamate analogues to piperidine, the mechanisms involved in their acid decomposition, and the role in the reaction of the heteroatom at the 4-position.…”

Section: Introductionmentioning

confidence: 99%

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Mechanisms of Acid Decomposition of Dithiocarbamates. 5. Piperidyl Dithiocarbamate and Analogues

2008

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In this work, the acid cleavage at 25 degrees C in 20% v/v aqueous ethanol of a series of analogues of piperidine dithiocarbamate X(C2H4)2NCS2(-) (X = CH2, CHCH3, NH, NCH3, S, O) was studied. The pH-rate profiles were obtained in the range of H(o)-5 and pH 5. They all presented a dumbell shaped curve with a plateau from which the pH-independent first-order rate constant k(o) (or the specific acid catalysis k(H)) was calculated, in addition to the acid dissociation constant of the free (pKa) and conjugate acid (pK(+)) species of the DTC. LFERs of the kinetically determined pKa and pK(+) versus pKN (pKa of parent amine) were used to characterize the reactive species and the structure of the transition state of the rate-determining step. For X = CH2, CH3CH the values of k(H) agree with those of alkDTCs in the strong base region of the Brønsted plot of log k(H) versus pKN where the transition state is close to a zwitterion formed by intramolecular water-catalyzed S-to-N proton transfer of the dithiocarbamic acid. However, when X = NH, CH 3N, O, S, the reactive species is the DTC anion, which is as reactive as an arylDTC, and similarly, the pK(+) values correspond to a parent amine that is about 3-4 pK units more basic. The solvent isotope effect indicated that the acid decomposition of these dithiocarbamate anions is specifically catalyzed by a Hydron anchimerically assisted by the heteroatom through a boat conformation.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Mechanisms of Acid Decomposition of Dithiocarbamates. 5. Piperidyl Dithiocarbamate and Analogues

2008

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“…glycinamide), 5-methylthiazole 13 (R1 = R2 = R3 = R4 = H) was obtained20 (Scheme 3) as the sole product.22 Evidently, steric factors influence reaction outcome (Table 3); the use of a more hindered amide, such as leucinamide (entry 2) instead of glycinamide (entry 1), still allowed for recovery of some penem compound. However, nucleophilic substitution at C-2 became the prevalent reaction only with the use of iV-alkyl (entries [3][4][5][6][7][8][9][10][11][12] or cyclic (entries 13-21) amino acid derivatives, bearing in any case a secondary nucleophilic nitrogen. Different alkyl substitutions on the nitrogen atom or -substitutions on the amino acid slightly influenced the reaction outcome (compare entries 3 os 4, 1 vs 2, and 3 vs 9), as did insertion of a different moiety on the carboxy group (entries 3 vs 10 and 11 and 14 vs 17).…”

Section: Chemistrymentioning

confidence: 99%

2-Substituted Penems with Amino Acid-Related Side Chains: Synthesis and Antibacterial Activity of a New Series of .beta.-Lactam Antibiotics

Altamura

Perrotta²,

Sbraci³

et al. 1995

J. Med. Chem.

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A new series of 6-(hydroxyethyl)penems 2-substituted with amino acid-related side chains was synthesized. The nature of the amino acyl derivative proved to be crucial both from a synthetic point of view, as beta-lactam ring opening can compete with C-2 nucleophilic substitution, and for antibacterial activity. Primary amino acid amides emerged as the most suitable side chains for enhancing permeability through a Gram-negative outer membrane. In vitro activity of the new 2-[(aminoamido)methyl]penems 3a-u was influenced by the nature and position of the amide moiety, the ring size for cyclic amides, and the configuration of the amino acid. Compounds bearing amides derived from small N-methyl amino acids (such as 3a) or from cyclic amino acids (such as prolinamide 3p and 4-hydroxyprolinamide 3r) showed broad spectrum in vitro activity against both Gram-positive and Gram-negative microorganisms.

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Some Inherently Chiral Chromophores—Empirical Rules and Quantum Chemical Calculations

Kwit

Skowronek

Gawroński

et al. 2012

Comprehensive Chiroptical Spectroscopy

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Synthesis of new penem dithiocarbamates

Cited by 13 publications

References 14 publications

Mechanisms of Acid Decomposition of Dithiocarbamates. 5. Piperidyl Dithiocarbamate and Analogues

Mechanisms of Acid Decomposition of Dithiocarbamates. 5. Piperidyl Dithiocarbamate and Analogues

2-Substituted Penems with Amino Acid-Related Side Chains: Synthesis and Antibacterial Activity of a New Series of .beta.-Lactam Antibiotics

Some Inherently Chiral Chromophores—Empirical Rules and Quantum Chemical Calculations

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