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. 2018 Oct 11;8(61):34903-34910.
doi: 10.1039/c8ra08165d. eCollection 2018 Oct 10.

One step access to oxindole-based β-lactams through Ugi four-center three-component reaction

Giulia Rainoldi  1 , Giordano Lesma  1 , Claudia Picozzi  2 , Leonardo Lo Presti  1 , Alessandra Silvani  1
Affiliations

One step access to oxindole-based β-lactams through Ugi four-center three-component reaction

Giulia Rainoldi et al. RSC Adv. .

Abstract

A multicomponent Ugi reaction involving isatin, isocyanide and β-amino acid components has been developed. The reactions proceeded smoothly to give β-lactam-containing 3,3-disubstituted oxindoles in only one step and generally high yields. When chiral, non racemic, β-amino acids were used, products were obtained as enantiomerically pure β-lactams diastereoisomers, whose relative stereochemistry was determined by X-ray analysis. For one compound, a weak antibacterial activity has been preliminarily highlighted.

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Conflict of interest statement

There are no conflicts to declare.

Figures

Fig. 1
Fig. 1. Examples of biologically relevant compounds containing β-lactam or 3-substituted-3-amino-2-oxindole fragments.
Scheme 1
Scheme 1. Components scope of the Ugi-4C-3CRa. aReaction conditions: isatin 1 (0.5 mmol), isocyanide 2 (0.5 mmol) and β-amino acid 3 (0.5 mmol) in TFE (1 mL), stirred at room temperature. Isolated yields are reported. PBB = p-bromobenzyl, PNB = p-nitrobenzyl.
Scheme 2
Scheme 2. Post-transformation reactions performed on selected compounds.
Fig. 2
Fig. 2. ORTEP view of compound 4oa with the atom-numbering scheme. The crystallographic reference system is also highlighted. Thermal ellipsoids of non-H atoms at RT were drawn at the 30% probability level.
Scheme 3
Scheme 3. Proposed mechanism for compound 6.
Fig. 3
Fig. 3. Drug- and lead-likeness (MW/log P) of all the products obtained in this work. Blue-spots: β-lactams derivatives 4a–p. Red-spots: post-transformation derivatives 5–7.
Fig. 4
Fig. 4. Calculated hydrogen bonding donators (HBD, blue-bars), hydrogen bonding acceptors (HBA, red-bars), and rotational bonds (RB, greenbars) for all the synthesized compounds.
See this image and copyright information in PMC

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