Sulfur-free Penicillin Derivatives. II. Functionalization of the Methyl Groups

1972 ◽  
Vol 50 (17) ◽  
pp. 2898-2902 ◽  
Author(s):  
Saul Wolfe ◽  
Wha Suk Lee ◽  
Jean-Bernard Ducep ◽  
Gérard Kannengiesser
Keyword(s):  
Carbonyl Group ◽  
Ring Opening ◽  
Methyl Groups ◽  
Cephalosporin C ◽  
Lactam Carbonyl Group ◽  
Molar Equivalent ◽  
Lactam Carbonyl

Allylic bromination of anhydropenicillin chlorination products by N-bromosuccinimide (NBS) is described. With two molar-equivalents of NBS both methyl groups are functionalized; with one molar-equivalent of NBS a mixture of Z and E monobrominated isomers is obtained.Nitrogen and oxygen nucleophiles attack the dibrominated derivatives at the β-lactam carbonyl group, with concomitant ring-opening. However, the mono-brominated derivatives undergo ready displacement by azide and formate ions. The mechanism of these reactions, leading to preferred formation of Z-isomer, is discussed.Cyclization of the allylic formates yields sulfur-free derivatives corresponding to the cephalosporin Cc class of compounds.

scholarly journals Fates of imine intermediates in radical cyclizations of N-sulfonylindoles and ene-sulfonamides

2015 ◽  
Vol 11 ◽  
pp. 1649-1655 ◽  
Author(s):  
Hanmo Zhang ◽  
E Ben Hay ◽  
Stephen J Geib ◽  
Dennis P Curran
Keyword(s):  
Carbonyl Group ◽  
Ring Opening ◽  
Radical Cyclizations ◽  
Type Reaction ◽  
Primary Products ◽  
Lactam Carbonyl Group ◽  
Lactam Carbonyl ◽  
Imine Reduction ◽  
Derivatives Of

Two new fates of imine intermediates formed on radical cyclizations of ene-sulfonamides have been identified, reduction and hydration/fragmentation. Tin hydride-mediated cyclizations of 2-halo-N-(3-methyl-N-sulfonylindole)anilines provide spiro[indoline-3,3'-indolones] or spiro-3,3'-biindolines (derived from imine reduction), depending on the indole C2 substituent. Cyclizations of 2-haloanilide derivatives of 3-carboxy-N-sulfonyl-2,3-dihydropyrroles also presumably form spiro-imines as primary products. However, the lactam carbonyl group facilitates the ring-opening of these cyclic imines by a new pathway of hydration and retro-Claisen-type reaction, providing rearranged 2-(2'-formamidoethyl)oxindoles.

scholarly journals Intramolecular Aza-Wittig Reaction of Iminophosphoranes with the b-Lactam Carbonyl Group

1997 ◽  
Author(s):  
Mateo Alajarín ◽  
Pedro Molina ◽  
Angel Vidai ◽  
Fulgencio Tovar
Keyword(s):  
Carbonyl Group ◽  
Wittig Reaction ◽  
Lactam Carbonyl Group ◽  
Lactam Carbonyl

ChemInform Abstract: The First Aza-Wittig Reaction of the β-Lactam Carbonyl Group.

ChemInform ◽  
2010 ◽  
Vol 30 (8) ◽  
pp. no-no
Author(s):  
M. ALAJARIN ◽  
P. MOLINA ◽  
A. VIDAL ◽  
F. TOVAR
Keyword(s):  
Carbonyl Group ◽  
Wittig Reaction ◽  
Lactam Carbonyl Group ◽  
Lactam Carbonyl

Studies on the ring-opening of bicyclic cyclopropanes activated by a carbonyl group

2013 ◽  
Vol 54 (14) ◽  
pp. 1798-1801 ◽  
Author(s):  
Xiaojian Jiang ◽  
Zonghan Lim ◽  
Ying-Yeung Yeung
Keyword(s):  
Carbonyl Group ◽  
Ring Opening

Recent Advances in the Chemistry of 2-Acylaziridines

Synthesis ◽  
2017 ◽  
Vol 49 (23) ◽  
pp. 5093-5104 ◽  
Author(s):  
Alena Pankova ◽  
Mikhail Kuznetsov
Keyword(s):  
Carbonyl Group ◽  
Ring Opening ◽  
Bond Cleavage ◽  
Aziridine Ring ◽  
Reaction Selectivity ◽  
Recent Advances ◽  
Nitrogen Containing Compounds

This review highlights recent achievements in the transformations of 2-acylaziridines toward the synthesis of cyclic and acyclic nitrogen-containing compounds. The influence of a carbonyl group on reaction selectivity is discussed.1 Introduction2 Reactions via C–C Bond Cleavage3 Reactions via C–N Bond Cleavage3.1 Reactions Starting with the Aziridine Ring Opening3.2 Reactions Starting at the Carbonyl Group4 Conclusion

Rate–acidity profiles for exchange of the 4-methyl protons in amino, imino, and keto pyrimidines

1979 ◽  
Vol 57 (20) ◽  
pp. 2783-2789 ◽  
Author(s):  
Ross Stewart ◽  
Stewart J. Gumbley ◽  
R. Srinivasan
Keyword(s):  
Aqueous Solution ◽  
Carbonyl Group ◽  
Principal Components ◽  
Kinetic Isotope Effect ◽  
Activation Parameters ◽  
Methyl Groups ◽  
Imino Group ◽  
Hydroxide Ion ◽  
Kinetic Isotope ◽  
Amino Pyrimidine

The rate of exchange of deuterium for protium in the 4-methyl groups of 2-imino-1,4-dimethyl-1,2-dihydropyrimidine (1), 1,4-dimethyl-2-pyrimidone (2), and 4-methyl-2-amino-pyrimidine (3) has been determined in aqueous solution over an acidity range of some 21 pH(H0) units. The various exchange routes involve attack by base (water, hydroxide ion, buffer anion) on substrate (neutral, singly protonated, doubly protonated) and the identities of the principal components across the acidity spectrum have been established for all three compounds. The Brønsted slope, kinetic isotope effect, and activation parameters for 1 have also been determined. Protonating 1 activates it toward exchange by a factor of 103; addition of a second proton has a further effect of >105. The activating effects of the imino group, the carbonyl group, and the protonated imino group in these compounds are in the ratio 10−1:1:102.

scholarly journals Towards Synthesis of Simplified Analogues of Pateamine A

2021 ◽  
Author(s):  
◽  
Tao Xu
Keyword(s):  
Ring Opening ◽  
Side Chain ◽  
Methyl Groups ◽  
Chain Fragment ◽  
Unsaturated Lactone ◽  
Structure Activity ◽  
Potent Inhibition ◽  
Nonsense Mediated Mrna Decay ◽  
Pateamine A ◽  
Future Work

<p>Pateamine A (22) is a natural product that was isolated from a marine sponge inhabiting the coast of New Zealand. It exhibits potent inhibition of protein synthesis and nonsense-mediated mRNA decay through binding with eIF4A isoforms. Due to the scarcity of pateamine A (22) in the natural source and the low yield of total synthesis of pateamine A, it is necessary to prepare structurally simplified analogues which would allow further research on structure-activity relationships (SAR) of pateamine A (22). Based on the structure-activity relationship studies reported by Romo and co-workers, a simplified triazole analogue 182 lacking methyl groups was synthesized by Hemi Cumming, a previous Ph.D. student who studied at Victoria University of Wellington. The antiproliferative activity of this analogue was found to be significantly lower than that of pateamine A, suggesting that the thiazole embedded within the molecule or the excised methyl groups are crucial for its potency.   Therefore, to further explore the necessary features for its selective activity for eIF4A isoforms, new thiazole analogues 183 – 186 and triazole analogues (10S)-and (10R)-analogue 187 were targeted in this project.    The preparation of the thiazole-containing macrocyclic core of analogues 183 and 184 was achieved. It features: (1) gold-catalysed thiazole formation through coupling between an alkyne fragment and a thioamide fragment; (2) preparation of the Z,E-dienoate moiety by base-induced ring-opening of a δ-substituted-α, β-unsaturated lactone; and (3) a modified Mukaiyama macrolactonisation. The synthesis of the triazole-containing macrocyclic core of (10S)-analogue 187 was completed. It features: (1) a copper-catalysed triazole formation through 1,3-dipolar cycloaddition between an alkyne fragment and an azide fragment; (2) preparation of the Z,E-dienoate moiety by base-induced ring-opening of δ-substituted-α, β-unsaturated lactone; and (3) a modified Mukaiyama macrolactonisation. Studies on the preparation of a side-chain fragment with suitable functionalities to allow coupling with the various macrocycles through olefination reactions were also conducted.  The attachment of the side-chain fragment onto the macrocyclic cores for the synthesis of the targeted analogues 183 and 184 and (10S)-analogue 187 will be investigated in future work. These experimental results will inform the synthesis of new generation analogues to further study the key structures required for effective binding to the protein target eIF4A and selectivity between isoforms.</p>

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