In the context of our work on photocleavable fragrance precursors, we have discovered a new photo-fragmentation of xanthenoic esters into xanthene- and formyl radicals. This homolytic cleavage has not been reported previously. Thus, unsaturated formyl radicals cyclise to lactones of various ring size.

As part of a programme evaluating medium-ring lactams as peptide conformational constraints the trans-disubstituted lactam dipeptide (3S,8R)-3-acetylamino-8-methoxycarbamoylazocan-2-one (3) was selected as a template to mimic the type VI β-turn conformation of natural polypeptides. The enantioselective synthesis of the eight-membered lactam 3 is discussed. The X-ray crystal structure of the methyl ester precursor of 3 shows a classical type VIb β-turn conformation. Extensive 1H NMR spectroscopic studies of the dipeptide 3 in polar solvents provided evidence for a type VI β-turn. The analysis shows an equilibrium of two folded conformations.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

The eight-membered lactam dipeptide (3R,8R)-3-acetylamino-8-methoxycarbamoylazocan-2-one was prepared from the L-serine derived (4S)-3-tert-butyloxycarbonyl-4-formyl-2,2-dimethyl-1,3-oxazolidine in 12 steps and 27% overall yield. An extensive conformational analysis both in the solid state and in solution, using NMR, IR and vapour pressure osmometry, was conducted. It was shown that the constrained dipeptide exists in a semi-extended conformation and exhibits a head-to-tail self-recognition (K-dim 100+/-20 dm(3) mol(-1) in CDCl2CDCl2). This dimerisation appears to be a general phenomenon in a series of cis-disubstituted medium-ring lactam dipeptides.

As part of project evaluating medium-ring lactams as constrained peptidomimetics, a novel method for the formation of multisubstituted eight-membered lactams has been developed. N-Protected 7-amino-8-hydroxyoctenoic acids were cyclised to give 8-amino-5,6-dehydro-2-oxocanones which underwent clean intramolecular O-to-N-acyl (lactone-to-lactam) ring contraction to yield 8-hydroxymethyl-6,7-dehydro-2-azocanones, suitable for elaboration to eight-membered lactam dipeptides.

The enantioselective synthesis of (+)-laurencin 1 has been achieved in 27 steps from (R)-malic acid 20. The key steps involved methylenation of the lactone 49 followed by intramolecular hydrosilation of the enol ether 14 (Scheme 11) and one carbon homologation of the diol 13 to give the key ethyl substituted cyclic ether 59 (Scheme 13). The lactone 49 was obtained by two efficient routes, namely a Claisen ring expansion (Scheme 3) followed by α-hydroxylation (Scheme 6) and a Yamaguchi lactonization (Scheme 11). Elaboration of the (E)-pentenynyl side chain (Scheme 18) and introduction of bromine (Scheme 19) completed the synthesis of (+)-laurencin 1.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ADVERTISEMENT RETURN TO ISSUEPREVAddition/CorrectionNEXTSynthesis of (+)-LaurencinA Retraction J. Am. Chem. Soc. 1993, 115, 10400−10401Jonathan W. Burton, J. Stephen Clark, Justin Bendall, Sam Derrer, Thomas Stork, and Andrew B. HolmesCite this: J. Am. Chem. Soc. 1996, 118, 28, 6806Publication Date (Web):July 17, 1996Publication History Published online17 July 1996Published inissue 1 January 1996https://pubs.acs.org/doi/10.1021/ja965406jhttps://doi.org/10.1021/ja965406jcorrectionACS PublicationsCopyright © 1996 American Chemical Society. This publication is available under these Terms of Use. Request reuse permissions This publication is free to access through this site. Learn MoreArticle Views1024Altmetric-Citations6LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail PDF (66 KB) Get e-Alertsclose Get e-Alerts

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

beta-Turns are ubiquitous in bioactive conformations of important peptides. We have designed a family of seven-membered lactam dipeptide mimics which are expected to act as conformational constraints in enforcing type VIa beta-turns in peptide chains. Molecular modelling using Macromodel predicts that both 3(S)-acetylamino-7(S)-carboxy-azepan-2-one N-methyl amide (1, the cis-disubstituted lactam, MM2) and 3 (S)-acetylamino-7(R)-carboxy-azepan-2-one N-methyl amide (2a, the trans-disubstituted lactam, MM2 and AMBER) should exhibit features of type VI beta-turns. The synthesis and structural analysis of the cis-(1) and trans-disubstituted (2) seven-membered lactam constraints are reported. X-Ray crystallographic analysis and solution NMR measurements offer insight into the preferred conformations of these molecules. Variable temperature NMR data and vapour pressure osmometry of 1 in solution indicate that it exhibits a strong cooperative recognition phenomenon to form a novel dimer, a feature not demonstrated by the trans-isomer 2a, which has a type VIa beta-turn-like conformation in the solid state. These phenomena can be realistically modelled in molecular dynamics simulations, and demonstrate potential for the design of new materials by self-assembly.