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Author

Heinz Heimgartner

Bio: Heinz Heimgartner is an academic researcher from University of Zurich. The author has contributed to research in topics: Cycloaddition & Azirine. The author has an hindex of 36, co-authored 815 publications receiving 8102 citations. Previous affiliations of Heinz Heimgartner include Saint Petersburg State University & Centre national de la recherche scientifique.
Topics: Cycloaddition, Azirine, Amide, Ring (chemistry), Ylide


Papers
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Journal ArticleDOI
TL;DR: 3-Amino-2H-azirines are ideal synthons for the construction of oligopeptides, cyclic peptides and depsipeptides (peptolides) containing such alpha,alpha-disubstituted alpha-amino acids and can be used in peptide coupling without the need for additional activating reagents.
Abstract: The recent upswing in peptide chemistry has been accompanied by an increasing interest in nonproteinogenic amino acids. These include the alpha,alpha-disubstituted glycines, the best known of which is Aib (2-aminoisobutyric acid, 2-methylalanine). These alpha-amino acids occur in natural oligopeptides such as the peptaibols, a class of membrane-active ionophores that has been isolated from fungal cultures. The twofold substitution at the alpha-C atom of the amino acids severely restricts the conformational freedom of the peptides and causes particular secondary structures to be favored; thus, alpha,alpha-disubstituted alpha-amino acids induce the formation of beta-turns or helices. 3-Amino-2H-azirines are ideal synthons for the construction of oligopeptides, cyclic peptides and depsipeptides (peptolides) containing such alpha,alpha-disubstituted alpha-amino acids. The presence of the ring strain in these molecules means that they can be used in peptide coupling without the need for additional activating reagents. Using 3-amino-2H-azirines a large array of heterocycles containing alpha,alpha-disubstituted alpha-amino acids as structural elements within their skeleton can be synthesized. The driving force in these reactions is the release of the strain on the three-membered ring, which usually takes place in a ring-expansion reaction. The mechanistic elucidation of these reactions, which can be quite complex, contains some surprises.

204 citations

Journal ArticleDOI
TL;DR: A wide range of cyclic and open-chain alpa, alpha-disubstituted alpha-amino acids 1a-p were prepared and the absolute configurations of the alpha,alpha-disubsided amino acids were determined from X-ray structures of the diastereoisomers 20, 21g', 22d.
Abstract: A wide range of cyclic and open-chain alpa,alpha-disubstituted alpha-amino acids 1a-p were prepared. The racemic N-acylated alpha,alpha-disubstituted amino acids were resolved by coupling to chiral amines 15-18 derived from (S)- phenylalanine to form diastereoisomers 19/20 or 21/22 that could be separated by crystallization and/or flash chromatography on silica gel (Scheme 3). Selective cleavage via the 1,3-oxazol-5(4H)-ones 10a-p gave the corresponding optically pure alpha,alpha-disubstituted amino-acid derivatives 11 or 12 in high yield (Scheme 3). The absolute configurations of the alpha,alpha-disubstituted amino acids were determined from X-ray structures of the diastereoisomers 20, 21g', 22d.

75 citations

Journal ArticleDOI
TL;DR: The main problem of this coupling reaction is the epimerization of the nonterminal amino acid in 4via a mechanism shown in Scheme 1.
Abstract: Peptide-Bond Formation with C-Terminal α,α-Disubstituted α - Amino Acids via Intermediate Oxazol-5(4H)-ones The formation of peptide bonds between dipeptides 4 containing a C-terminalα,α-disubstituted α-amino acid and ethyl p-aminobenzoate (5) using DCC as coupling reagent proceeds via 4,4-disubstituted oxazol-5(4H)-ones 7 as intermediates (Scheme 3). The reaction yielding tripeptides 6 (Table 2) is catalyzed efficiently by camphor-10-sulfonic acid (Table 1). The main problem of this coupling reaction is the epimerization of the nonterminal amino acid in 4via a mechanism shown in Scheme 1. CSA catalysis at 0° suppresses completely this troublesome side reaction. For the coupling of Z-Val-Aib-OH (11) and Fmoc-Pro-Aib-OH (14) with H-Gly-OBu1 (12) and H-Ala-Aib-NMe2 (15), respectively, the best results have been obtained using DCC in the presence of ZnCl2 (Table 3).

74 citations

Journal ArticleDOI
TL;DR: In this article, photochemically induced reactions of 3-Amino-2H-azirines with a mercury low pressure lamp have been studied and shown to yield 5-membered heterocycles with high regioselectivity.
Abstract: Photochemically Induced Reactions of 3-Amino-2H-azirines Irradiation of 3-(N-methylanilino)-2H-azirines with a mercury low pressure lamp induces the cleavage of the C(2), C(3)-ring bond thus affording nitrilio-methanide dipols, substituted by an amino group at C(1). Depending on the substitution pattern at C(3), these intermediates can be trapped by dipolarophiles to yield five-membered heterocycles with high regioselectivity, or they undergo a 1,4-H-shift forming 2-azabutadiene derivatives. Further, the dipol is protonated at C(1) even by weak CH–acids.

72 citations

Journal ArticleDOI
TL;DR: In this article, a large array of heterocycles containing α,α-disubstituted α-amino acids as structural elements within their skeleton can be synthesized.
Abstract: 3-Amino-2H-azirines are ideal synthons for the construction of oligopeptides, cyclic peptides and depsipeptides (peptolides) containing α,α-disubstituted α-amino acids. The presence of the ring strain in these molecules means that they can be used in peptide coupling without the need for additional activating reagents. Using 3-amino-2H-azirines a large array of heterocycles containing α,α-disubstituted α-amino acids as structural elements within their skeleton can be synthesized. The driving force in these reactions is the release of the strain on the three-membered ring, which usually takes place in a ring-expansion reaction. The mechanistic elucidation of these reactions, which can be quite complex, contains some surprises

66 citations


Cited by
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[...]

08 Dec 2001-BMJ
TL;DR: There is, I think, something ethereal about i —the square root of minus one, which seems an odd beast at that time—an intruder hovering on the edge of reality.
Abstract: There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality. Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …

33,785 citations

Journal ArticleDOI
01 Apr 1988-Nature
TL;DR: In this paper, a sedimentological core and petrographic characterisation of samples from eleven boreholes from the Lower Carboniferous of Bowland Basin (Northwest England) is presented.
Abstract: Deposits of clastic carbonate-dominated (calciclastic) sedimentary slope systems in the rock record have been identified mostly as linearly-consistent carbonate apron deposits, even though most ancient clastic carbonate slope deposits fit the submarine fan systems better. Calciclastic submarine fans are consequently rarely described and are poorly understood. Subsequently, very little is known especially in mud-dominated calciclastic submarine fan systems. Presented in this study are a sedimentological core and petrographic characterisation of samples from eleven boreholes from the Lower Carboniferous of Bowland Basin (Northwest England) that reveals a >250 m thick calciturbidite complex deposited in a calciclastic submarine fan setting. Seven facies are recognised from core and thin section characterisation and are grouped into three carbonate turbidite sequences. They include: 1) Calciturbidites, comprising mostly of highto low-density, wavy-laminated bioclast-rich facies; 2) low-density densite mudstones which are characterised by planar laminated and unlaminated muddominated facies; and 3) Calcidebrites which are muddy or hyper-concentrated debrisflow deposits occurring as poorly-sorted, chaotic, mud-supported floatstones. These

9,929 citations

Journal Article
TL;DR: This volume is keyed to high resolution electron microscopy, which is a sophisticated form of structural analysis, but really morphology in a modern guise, the physical and mechanical background of the instrument and its ancillary tools are simply and well presented.
Abstract: I read this book the same weekend that the Packers took on the Rams, and the experience of the latter event, obviously, colored my judgment. Although I abhor anything that smacks of being a handbook (like, \"How to Earn a Merit Badge in Neurosurgery\") because too many volumes in biomedical science already evince a boyscout-like approach, I must confess that parts of this volume are fast, scholarly, and significant, with certain reservations. I like parts of this well-illustrated book because Dr. Sj6strand, without so stating, develops certain subjects on technique in relation to the acquisition of judgment and sophistication. And this is important! So, given that the author (like all of us) is somewhat deficient in some areas, and biased in others, the book is still valuable if the uninitiated reader swallows it in a general fashion, realizing full well that what will be required from the reader is a modulation to fit his vision, propreception, adaptation and response, and the kind of problem he is undertaking. A major deficiency of this book is revealed by comparison of its use of physics and of chemistry to provide understanding and background for the application of high resolution electron microscopy to problems in biology. Since the volume is keyed to high resolution electron microscopy, which is a sophisticated form of structural analysis, but really morphology in a modern guise, the physical and mechanical background of The instrument and its ancillary tools are simply and well presented. The potential use of chemical or cytochemical information as it relates to biological fine structure , however, is quite deficient. I wonder when even sophisticated morphol-ogists will consider fixation a reaction and not a technique; only then will the fundamentals become self-evident and predictable and this sine qua flon will become less mystical. Staining reactions (the most inadequate chapter) ought to be something more than a technique to selectively enhance contrast of morphological elements; it ought to give the structural addresses of some of the chemical residents of cell components. Is it pertinent that auto-radiography gets singled out for more complete coverage than other significant aspects of cytochemistry by a high resolution microscopist, when it has a built-in minimal error of 1,000 A in standard practice? I don't mean to blind-side (in strict football terminology) Dr. Sj6strand's efforts for what is \"routinely used in our laboratory\"; what is done is usually well done. It's just that …

3,197 citations

Journal ArticleDOI
TL;DR: In this Review, the fundamental characteristics of azide chemistry and current developments are presented and the focus will be placed on cycloadditions (Huisgen reaction), aza ylide chemistry, and the synthesis of heterocycles.
Abstract: Since the discovery of organic azides by Peter Griess more than 140 years ago, numerous syntheses of these energy-rich molecules have been developed. In more recent times in particular, completely new perspectives have been developed for their use in peptide chemistry, combinatorial chemistry, and heterocyclic synthesis. Organic azides have assumed an important position at the interface between chemistry, biology, medicine, and materials science. In this Review, the fundamental characteristics of azide chemistry and current developments are presented. The focus will be placed on cycloadditions (Huisgen reaction), aza ylide chemistry, and the synthesis of heterocycles. Further reactions such as the aza-Wittig reaction, the Sundberg rearrangement, the Staudinger ligation, the Boyer and Boyer-Aube rearrangements, the Curtius rearrangement, the Schmidt rearrangement, and the Hemetsberger rearrangement bear witness to the versatility of modern azide chemistry.

1,766 citations

Journal ArticleDOI
TL;DR: Molecules bearing a trifluoromethyl group constitute one of the most important classes of selectively fluorinated compounds, and derivatives bearing the CF3 group on aromatic rings are particularly numerous and important.
Abstract: “All new is well-forgotten old”, the proverb goes. The current “fluorine boom” is news only to a novice in the field: the exceptional importance of fluorinated organic compounds in numerous areas has been known for a long time. The sharpest increase in the number of fluorine-containing pharmaceuticals and agrochemicals is dated back to 30 years ago. Also around that time (1979), the first monograph devoted to industrial applications of organofluorine compounds was published, covering not only fluorine-containing biologically active materials but also refrigerants, propellants, surfactants, textile chemicals, polymers, and dyes. The increasingly broad realization of the key role of organofluorine compounds in numerous areas has recently attracted many new scientists to the field. The development of new methods for the selective introduction of fluorine and fluorinecontaining groups into organic molecules for biologically active and other useful materials has become a hot area. Over 100 reviews, book chapters, and highlights on this subject have appeared in the literature in the past few years. As citing all of these publications in this review article is impossible, we provide references to only the most recent, general, and comprehensive ones. Molecules bearing a trifluoromethyl group constitute one of the most important classes of selectively fluorinated compounds. As early as 1928, Lehmann reported his observations of biological activity of some trifluoromethylated organic derivatives and already in 1959 Yale published a detailed review article entitled “The Trifluoromethyl Group in Medicinal Chemistry”. Since then, numerous books and reviews have appeared in the literature covering various aspects of trifluoromethylated organic and organometallic compounds. Within this family, derivatives bearing the CF3 group on aromatic rings are particularly numerous and important. Some examples of such compounds used as active ingredients of pharmaceuticals and agrochemicals are shown in Scheme 1. Trifluoromethylated building blocks and intermediates are clearly needed to make such molecules. The simplest trifluoromethylated aromatic compound, benzotrifluoride, was originally prepared by Swarts at the end of the 19th century. In his work, Swarts treated benzotrichloride with “two thirds of its weight of antimony fluoride” to obtain a mixture of PhCF2Cl and PhCF3, from which the two were separated and isolated pure by distillation. In the early 1930s, two industrial groups, one from Kinetic Chemicals, Inc. and one from I. G. Farbenindustrie AG patented their discoveries on the successful use of HF instead of SbF3 for the Swarts reaction. These inventions were the starting point for the modern large-scale manufacturing of trifluoromethylated aromatics. Other methods have been developed for conversion of various C1 units on the ring to CF3 with a variety of fluorinating agents. While representing an outstanding discovery and a classic of organic and organofluorine chemistry, the Swarts reaction is nonetheless neither atom-economical nor environmentally benign, as it deals with stoichiometric quantities of hazardous chemicals and generates large amounts of chlorine waste. To convert a CH3 group on the ring to CF3, the methyl is first exhaustively chlorinated to produce 3 equiv of HCl as a

1,383 citations