Ring-opening of some radicals containing the cyclopropylmethyl system

Beckwith, A. L. J.; Moad, Graeme

doi:10.1039/p29800001473

Cited by 50 publications

(19 citation statements)

References 3 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cyclopropyl-appended ACV variants have been used to probe the radical nature of the thiazolidine closure reaction in solution. [42] The cyclopropyl group is a useful probe for radicals as it readily forms but-3-enyl systems via a cyclopropylcarbinyl radical intermediate species, [43] the formation of which would lead to substrate conversion to an unsaturated macrocyclic product. [41,42] Extending this into crystallographic studies, Howard-Jones et al (2007) worked with ACV analogues incorporating cyclopropyl groups in the third residue: δ-(l-α-aminoadipoyl)-l-cysteinyl-β-methyl-d-cyclopropylglycine (ACmcpG, 30; Figure 16A) and δ-(l-α-aminoadipoyl)-l-cysteinyl-d-cyclopropylglycine (ACcpG, 32; Figure 16B).…”

Section: Substrate Analogues With Altered Steric Profilesmentioning

confidence: 99%

“…Cyclopropyl‐appended ACV variants have been used to probe the radical nature of the thiazolidine closure reaction in solution [42] . The cyclopropyl group is a useful probe for radicals as it readily forms but‐3‐enyl systems via a cyclopropylcarbinyl radical intermediate species, [43] the formation of which would lead to substrate conversion to an unsaturated macrocyclic product [41,42] . Extending this into crystallographic studies, Howard‐Jones et al.…”

Section: Crystal Structures Of Ipns Complexes With Substrate and Product Analoguesmentioning

confidence: 99%

See 1 more Smart Citation

Isopenicillin N Synthase: Crystallographic Studies

Chapman

Rutledge

2021

ChemBioChem

View full text Add to dashboard Cite

Isopenicillin N synthase (IPNS) is a non-heme iron oxidase (NHIO) that catalyses the cyclisation of tripeptide δ-(l-α-aminoadipoyl)-l-cysteinyl-d-valine (ACV) to bicyclic isopenicillin N (IPN). Over the last 25 years, crystallography has shed considerable light on the mechanism of IPNS catalysis. The first crystal structure, for apo-IPNS with Mn bound in place of Fe at the active site, reported in 1995, was also the first structure for a member of the wider NHIO family. This was followed by the anaerobic enzyme-substrate complex IPNSÀ FeÀ ACV (1997), this complex plus nitric oxide as a surrogate for co-substrate dioxygen (1997), and an enzyme product complex (1999). Since then, crystallography has been used to probe many aspects of the IPNS reaction mechanism, by crystallising the protein with a diversity of substrate analogues and triggering the oxidative reaction by using elevated oxygen pressures to force the gaseous co-substrate throughout protein crystals and maximise synchronicity of turnover in crystallo. In this way, X-ray structures have been elucidated for a range of complexes closely related to and/or directly derived from key intermediates in the catalytic cycle, thereby answering numerous mechanistic questions that had arisen from solution-phase experiments, and posing many new ones. The results of these crystallographic studies have, in turn, informed computational experiments that have brought further insight. These combined crystallographic and computational investigations augment and extend the results of earlier spectroscopic analyses and solution phase studies of IPNS turnover, to enrich our understanding of this important protein and the wider NHIO enzyme family.

show abstract

Section: Substrate Analogues With Altered Steric Profilesmentioning

confidence: 99%

Section: Crystal Structures Of Ipns Complexes With Substrate and Product Analoguesmentioning

confidence: 99%

Isopenicillin N Synthase: Crystallographic Studies

Chapman

Rutledge

2021

ChemBioChem

View full text Add to dashboard Cite

show abstract

“…(11) (Scheme 2) became important at longer reaction times, as did a tribromide; probably (12). Retention time comparisons with authentic l-bromobicyclo[2.1.l]hexane (13) showed that none was detectable, i.e. the mol % of (13) was d 0.5.…”

Section: -Bromobicyclo[211]hexane (9) But the Dibromides (10) Andmentioning

confidence: 99%

Free radical reactions of bicyclo[2.1.1]hexane and bicyclo[2.2.1]heptane

Walton¹

1988

J. Chem. Soc., Perkin Trans. 2

View full text Add to dashboard Cite

t-Butoxyl radicals abstract hydrogen from C(2) of bicyclo[2.1 .l] hexane (3) to give bicyclo[2.1 .I] hexan-2-yl radicals (6). At T > 250 K radicals ( 6 ) rearrange b y p-scission t o cyclopent-3enylmethyl radicals; both species were observed b y e.p.r. spectroscopy. In spite of the much greater ring strain the activation energy for rearrangement of (6) is about the same as that of cyclobutylmethyl radicals. Bromine atoms abstract hydrogen from C(2) of (3), but bis(trimethylsilyl)aminyl radicals abstract the bridgehead methine hydrogen at C ( l ) as well as the methylene hydrogens at C(2). There is very little abstraction of the bridgehead hydrogen in bicyclo[2.2.1] heptane b y bis(trimethylsilyl)aminyl radicals. Thus, the greater bridgehead reactivity of (3) as compared with the bridge positions is not simply due to the lower selectivity of the bis(trimethylsilyl)aminyl radicals, but is an intrinsic property of the bicycloalkane.

show abstract

“…Previous reports,'-5 have demonstrated that cyclobutylmethyl (and substituted cyclobutylmethyl) radicals (1) are prone to rapid ring-opening to give the isomer 2 by a process which is frequently, though not always,' irreversible. The rate constant for ring fission of the parent species 1,' for example, is 4.7 x lo3 s-' at 25 "C, and the activation energy of the rearrangement 1 -2 is 11.7 kcal mol-' (1 cal SE 4.18 J).…”

mentioning

confidence: 99%