N-acetyl-N-acyl-3-aminoquinazolinones as chemoselective acetylating agents

Atkinson, Robert S.; Barker, Emma; Sutcliffe, Michael J.

doi:10.1039/cc9960001051

Cited by 23 publications

(15 citation statements)

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“…4,5 Exhaustive literature survey reveals the applications of a variety of other catalysts also; these include 4-dialkylaminopyridine, 3 basic alumina, 6 perchloric acid adsorbed on silica gel, 7 In(OTf) 3 , 8 ruthenium(III)chloride, 9 montmorillonite K-10 and KSF, 10 (pyridine)(tetrahydroborato)zinc complex, 11 sodium dodecyl sulfate (SDS), 12 acetonyltriphenylphosphonium bromide, 13 and many others. [14][15][16][17][18][19] A number of alternative methods have also been reported for N-acetylation of primary and secondary amines, where a variety of acetylating agents other than the conventional acetic anhydride, such as ethyl trifluoroacetate, 20 ortho-substituted N,N-diacetylaniline, 21 dichlorotriphenylphosphorane in chloroform, 22 imidoylbenzotriazoles, 23 poly(3-acyl-2-oxazolone), 24 2-acyl-4,5-dichloropyridazine-3one, 25 N,N-dialkylformamide dimethyl acetal with primary amides, 26 N-acetyl-N-acyl-3-aminoquinazolinones, 27 N-methoxydiacetamide, 28 N-acyl-N- (2,3,4,5,6-pentafluorophenyl)methan esulphonamides, 29 and many others were used. [30][31][32] In spite of such developments, acetic anhydride (or acetyl chloride) is still regarded as the key N-acetylating agent, both in commercial and non-commercial sectors.…”

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confidence: 99%

Metal Acetate/Metal Oxide in Acetic Acid: An Efficient Reagent for the Chemoselective N-Acetylation of Amines under Green Conditions

Brahmachari

Laskar

Sarkar

2010

Journal of Chemical Research

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The use of catalytic amount of metal acetate or metal oxide in acetic acid is a new and highly efficient acetylating system for chemoselective N-acetylation of primary and secondary amines in excellent yields under reflux condition. No other solvent is required. The noted features of this method include mild reaction conditions, use of innocuous reagents, excellent yields, convenient work-up, and reuse of catalyst.

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confidence: 99%

Metal Acetate/Metal Oxide in Acetic Acid: An Efficient Reagent for the Chemoselective N-Acetylation of Amines under Green Conditions

Brahmachari

Laskar

Sarkar

2010

Journal of Chemical Research

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“…1, are highly chemoselective acylating agents for primary amines in the presence of secondary amines and for the less hindered of two secondary amines (Scheme 1). 1 When the two N-acyl groups in the DAQ are not identical, the N-N bond becomes a chiral axis with the two planes containing the quinazolinone and imide moieties orthogonal to one another. The barrier to N-N bond rotation is sufficiently high to allow separation of diastereoisomers (atropisomers) when there is a chiral centre also present in the DAQ.…”

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confidence: 99%

Stereoisomerism in 3-[N-(2-acetoxypropanoyl)-N-acylamino]quinazolin-4(3H )-ones, enantioselective acylating agents

Al‐Sehemi

Atkinson

Fawcett

et al. 2000

J. Chem. Soc., Perkin Trans. 1

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The title compounds diacylaminoquinazolinones (DAQs) are enantioselective acylation agents for amines and a detailed study of their stereostructures was undertaken with the aim of understanding how this enantioselectivity arises. The N-N bond in these DAQs is a chiral axis. Even where both N-acyl groups are (S)-2-acetoxypropanoyl, the N-N bond is still a chiral axis because in the most stable conformation of the planar imide moiety, one exo/endo orientation of the carbonyl groups is much preferred over the alternative (endo/exo) as revealed by NMR spectroscopy. A conformational preference within the 2-acetoxypropanoyl grouping accounts for the presence of a single exo/endo conformation in solution for some of these DAQs (see above) but an interconverting exo/endo endo/exo mixture for others. Where a single exo/endo conformation is present in solution, evidence is presented that this closely resembles the X-ray determined crystal structure. A mechanism for the second acylation step to form these DAQs is proposed, which involves preliminary O-acylation of the 3-(monoacylamino)quinazolinone.

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“…Although this amine is resistant to acylation by activated Fmoc amino acids, it is reactive toward nitrophenylchloroformate for activation and would likely be modified by standard acetic anhydride/DMF acetylation cocktails. Atkinson et al describe mild acetylation conditions that are selective for primary amines in the presence of more hindered secondary amines using N ‐acetyl‐ N ‐acyl‐3‐aminoquinazolinones,9 for example commercially‐available DAAQ,9 which we reasoned would have selectivity for the N‐terminus over the Dbz linker (Scheme ).…”

Section: Resultsmentioning

confidence: 99%

Alternative chemistries for the synthesis of thrombospondin‐1 type 1 repeats

Tiefenbrunn¹,

Blanco‐Canosa²,

Dawson³

2010

Biopolymers

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Synthetic protein engineering has benefited from the development of diverse methods for the synthesis of functionalized peptide fragments and approaches for their subsequent assembly into full length polypeptides. Here we describe a series of synthetic approaches for the total chemical synthesis of the second type 1 repeat of thrombospondin‐1 (TSR2) that vary in both the location of the ligation site and α‐amine protecting group strategy (Boc/Fmoc) used for the synthesis of the associated peptide fragments. These syntheses illustrate that challenging peptide sequences can result from the protecting group strategy as well as from sequence‐dependent factors. Importantly, we find that such challenges can be overcome by altering the chemistry used for solid phase peptide synthesis, the choice of ligation site, and the resin used as a solid support. From these studies, we have developed a robust synthetic route to the TSR2 polypeptide consisting of native chemical ligation between an N‐terminal fragment synthesized by Boc‐SPPS and a C‐terminal fragment synthesized by Fmoc‐SPPS. Finally, the folded TSR2 domain is obtained following an optimized oxidative folding protocol using an excess of oxidized glutathione. This optimized synthesis will enable the use of unnatural amino acids to probe the unusual structure and anti‐angiogenic activity of this protein domain. © 2010 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 94: 405–413, 2010.

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N-acetyl-N-acyl-3-aminoquinazolinones as chemoselective acetylating agents

Abstract: The title compounds, e.g. 3, are highly selective acetylating agents for primary amines in the presence of secondary amines and, in particular, for the less sterically hindered of two different secondary amines.

Cited by 23 publications

References 2 publications

Metal Acetate/Metal Oxide in Acetic Acid: An Efficient Reagent for the Chemoselective N-Acetylation of Amines under Green Conditions

Metal Acetate/Metal Oxide in Acetic Acid: An Efficient Reagent for the Chemoselective N-Acetylation of Amines under Green Conditions

Stereoisomerism in 3-[N-(2-acetoxypropanoyl)-N-acylamino]quinazolin-4(3H )-ones, enantioselective acylating agents

Alternative chemistries for the synthesis of thrombospondin‐1 type 1 repeats

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