- Chemoenzymatic enantioselective route to get (+) and (?) 4-acetoxy-azetidin-2-one by lipase-catalysed kinetic resolution and their applications
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4-Acetoxy-azetidin-2-one is an extremely useful intermediate widely applied for the synthesis of several biologically active β-lactam compounds. However, it is available as a racemic mixture that could limit its application in the synthesis of enantiopure products. Herein we evaluated the use of lipases in a kinetic resolution (KR) process to finally obtain 4-acetoxy-zetidin-2-one as separated pure enantiomers. From a preliminary screening on a set of commercial enzymes, Pseudomonas fluorescens emerged as the most suitable lipase that allowed to obtain good conversions and excellent enantiomeric excesses. On the enantiomerically pure 4-acetoxy-azetidin-2-ones some nucleophilic substitutions and N-thio-alkylation reactions were tested in order to evaluate the stereochemical integrity at the C-4 position.
- Martelli, Giulia,Cirillo, Martina,Giraldi, Valentina,Giacomini, Daria
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- New β-Lactam Derivatives Modulate Cell Adhesion and Signaling Mediated by RGD-Binding and Leukocyte Integrins
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A novel series of β-lactam derivatives that was designed and synthesized to target RGD-binding and leukocyte integrins is reported. The compound library was evaluated by investigating the effects on integrin-mediated cell adhesion and cell signaling in cell lines expressing αvβ3, αvβ5, αvβ6, α5β1, αIIbβ3, α4β1, and αLβ2 integrins. SAR analysis of the new series of azetidinones enabled the recognition of structural elements associated with integrin selectivity. We obtained selective and potent agonists that could induce cell adhesion and promote cell signaling mediated by αvβ3, αvβ5, α5β1, or α4β1 integrin, and antagonists for the integrins αvβ3 and α5β1, as well as α4β1 and αLβ2, preventing the effects elicited by the respective endogenous agonists.
- Baiula, Monica,Galletti, Paola,Martelli, Giulia,Soldati, Roberto,Belvisi, Laura,Civera, Monica,Dattoli, Samantha Deianira,Spampinato, Santi Mario,Giacomini, Daria
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p. 9221 - 9742
(2016/11/19)
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- Targeting integrins αvβ3 and α5β1 with new β-lactam derivatives
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The αvβ3 and α5β 1 integrins are widely expressed in different cancer types and recognize the tripeptide Arg-Gly-Asp (RGD) motif present in several extracellular matrix proteins. We report here the design, synthesis and biological activity of some new β-lactam derivatives specifically designed to target integrins. The new molecules contain the azetidinone as the only cyclic framework armed with carboxylic acid and amine terminals spaced from 9 to 14 atoms to switch on recognition by integrins. All tested molecules showed a concentration-dependent enhancement in fibronectin-mediated adhesion of K562 and SK-MEL-24 cells; in particular 1, expressed a higher affinity towards α5β1 integrin (EC50 of 12 nM) and 2 was more selective for integrin αvβ3 (EC 50 of 11 nM).
- Galletti, Paola,Soldati, Roberto,Pori, Matteo,Durso, Margherita,Tolomelli, Alessandra,Gentilucci, Luca,Dattoli, Samantha Deianira,Baiula, Monica,Spampinato, Santi,Giacomini, Daria
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p. 284 - 293
(2014/07/08)
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- Cycloadditions in Syntheses. Part 28. 2-Azabicyclohexane-3,5-dione and its Derivatives: Synthesis and Transformation to Azetidin-2-ones
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2-Azabicyclohexane-3,5-dione has been synthesized via photopyridone formation from 4-(dimethyl-t-butylsiloxy)- or 4-alkoxy-2-pyridones followed by mild acid hydrolysis.The title compound and its derivatives react with a variety of nucleophiles (ROH
- Katagiri, Nobuya,Sato, Masayuki,Yoneda, Naoki,Saikawa, Satoshi,Sakamoto, Toshiyuki,et al.
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p. 1289 - 1296
(2007/10/02)
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- Cycloadditions in Syntheses. Part 27. rel-(1R,4R,5S)-5-Hydroxy-2-azabicyclohexan-3-one and its Derivatives: Synthesis and Transformation to Azetidin-2-ones
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The title compound, a synthetic equivalent of 4-(2-oxoethyl)azetidin-2-one, has been synthesized as a stable crystalline compound from the 2-pyridone having an appropriately protected 4-hydroxy group via photopyridine formation, catalytic hydrogenation, a
- Kaneko, Chikara,Katagiri, Nobuya,Sato, Masayuki,Muto, Makoto,Sakamoto, Toshiyuki,et al.
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p. 1283 - 1288
(2007/10/02)
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- 2-Azabicyclohexane-3,5-dione, a New Building Block for Carbapenem Nuclei
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2-Azabicyclohexane-3,5-dione is synthesized via photopyridone formation from 4-(t-butyldimethylsilyloxy)- or 4-alkoxy-2-pyridone followed by mild acid hydrolysis and reacts with a variety of alcohols or thiols to give 4-alkoxycarbonyl- or 4-alkylth
- Katagiri, Nobuya,Sato, Masayuki,Saikawa, Satoshi,Sakamoto, Toshiyuki,Muto, Makoto,Kaneko, Chikara
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p. 189 - 190
(2007/10/02)
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- rel-(1R,4R,5S)-5-HYDROXY-3-OXO-2-AZABICYCLOHEXANE, A STABLE SYNTHETIC EQUIVALENT OF 4-(2-OXOETHYL)AZETIDIN-2-ONE
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The title compound, a synthetic equivalent of 4-(2-oxoethyl)-azetidin-2-one, has been synthesized as a stable crystalline solid either from 4-(t-butyldimethylsilyloxy)- or 4-benzyloxy-2-pyridone via photopyridone formation, catalytic hydrogenation, and de
- Katagiri, Nobuya,Sato, Masayuki,Naito, Toshihiko,Muto, Makoto,Sakamoto, Toshiyuki,et al.
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p. 5665 - 5668
(2007/10/02)
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- Olivanic Acid Analogues. Part 1. Total Synthesis of the 7-Oxo-1-azabicyclohept-2-ene-2-carboxylate System and Some Related β-Lactams
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4-Allylazetidin-2-one, prepared from penta-1,4-diene and chlorosulphonyl isocyanate, has been used to synthesise the parent 7-oxo-1-azabicyclohept-2-ene-2-carboxylate system of the naturally occurring olivanic acids, using an intramolecular Wittig reaction to construct the 2,3-double bond.Cyclisation of ketones derived from the 4-allyl grouping produced 3-substituted derivatives, while use of the azetidin-2-one prepared from hexa-1,5-diene and chlorosulphonyl isocyanate has given the homologous 8-oxo-1-azabicyclooct-2-ene system.
- Bateson, John H.,Baxter, Andrew J. G.,Roberts, Patricia M.,Smale, Terence C.,Southgate, Robert
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p. 3242 - 3249
(2007/10/02)
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