Synthesis of highly substituted 1,2-diazetidin-3-ones, small ring scaffolds for drug discovery

1,2-Diazetidin-3-ones are readily accessible, small ring scaffolds that upon functionalization have the potential to produce diverse 3-dimensional structures for drug discovery. Thus treatment of diazo hydrazides, obtained from simple hydrazides and malonyl half ester derivatives, followed by diazo...

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Main Authors: Santos, Marilla S., Nortcliffe, Andrew, Lewis, William, Bradshaw, Tracey D, Moody, Christopher J.
Format: Article
Language:English
Published: Wiley-VCH Verlag 2018
Online Access:https://eprints.nottingham.ac.uk/51269/
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author Santos, Marilla S.
Nortcliffe, Andrew
Lewis, William
Bradshaw, Tracey D
Moody, Christopher J.
author_facet Santos, Marilla S.
Nortcliffe, Andrew
Lewis, William
Bradshaw, Tracey D
Moody, Christopher J.
author_sort Santos, Marilla S.
building Nottingham Research Data Repository
collection Online Access
description 1,2-Diazetidin-3-ones are readily accessible, small ring scaffolds that upon functionalization have the potential to produce diverse 3-dimensional structures for drug discovery. Thus treatment of diazo hydrazides, obtained from simple hydrazides and malonyl half ester derivatives, followed by diazo transfer, with catalytic amounts of rhodium (II) acetate dimer results in intramolecular carbenoid N–H insertion to give 1,2-diazetidin-3-ones. Although subsequent functionalization reactions could be hampered by the lability of the 4-membered ring, a wide range of new derivatives was available by deprotection at N-1, and subsequent amide or urea formation. The structures of four four-membered rings was confirmed by X-ray crystallography; the compounds showed modest growth inhibitory activity in mammary carcinoma cells.
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spelling nottingham-512692019-03-31T04:30:10Z https://eprints.nottingham.ac.uk/51269/ Synthesis of highly substituted 1,2-diazetidin-3-ones, small ring scaffolds for drug discovery Santos, Marilla S. Nortcliffe, Andrew Lewis, William Bradshaw, Tracey D Moody, Christopher J. 1,2-Diazetidin-3-ones are readily accessible, small ring scaffolds that upon functionalization have the potential to produce diverse 3-dimensional structures for drug discovery. Thus treatment of diazo hydrazides, obtained from simple hydrazides and malonyl half ester derivatives, followed by diazo transfer, with catalytic amounts of rhodium (II) acetate dimer results in intramolecular carbenoid N–H insertion to give 1,2-diazetidin-3-ones. Although subsequent functionalization reactions could be hampered by the lability of the 4-membered ring, a wide range of new derivatives was available by deprotection at N-1, and subsequent amide or urea formation. The structures of four four-membered rings was confirmed by X-ray crystallography; the compounds showed modest growth inhibitory activity in mammary carcinoma cells. Wiley-VCH Verlag 2018-03-31 Article PeerReviewed application/pdf en https://eprints.nottingham.ac.uk/51269/1/Chris%20Moody%20Synthesis%20of%20highly%20substituted%201.pdf Santos, Marilla S., Nortcliffe, Andrew, Lewis, William, Bradshaw, Tracey D and Moody, Christopher J. (2018) Synthesis of highly substituted 1,2-diazetidin-3-ones, small ring scaffolds for drug discovery. Chemistry - a European Journal . ISSN 1521-3765 https://onlinelibrary.wiley.com/doi/abs/10.1002/chem.201801309 doi:10.1002/chem.201801309 doi:10.1002/chem.201801309
spellingShingle Santos, Marilla S.
Nortcliffe, Andrew
Lewis, William
Bradshaw, Tracey D
Moody, Christopher J.
Synthesis of highly substituted 1,2-diazetidin-3-ones, small ring scaffolds for drug discovery
title Synthesis of highly substituted 1,2-diazetidin-3-ones, small ring scaffolds for drug discovery
title_full Synthesis of highly substituted 1,2-diazetidin-3-ones, small ring scaffolds for drug discovery
title_fullStr Synthesis of highly substituted 1,2-diazetidin-3-ones, small ring scaffolds for drug discovery
title_full_unstemmed Synthesis of highly substituted 1,2-diazetidin-3-ones, small ring scaffolds for drug discovery
title_short Synthesis of highly substituted 1,2-diazetidin-3-ones, small ring scaffolds for drug discovery
title_sort synthesis of highly substituted 1,2-diazetidin-3-ones, small ring scaffolds for drug discovery
url https://eprints.nottingham.ac.uk/51269/
https://eprints.nottingham.ac.uk/51269/
https://eprints.nottingham.ac.uk/51269/