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Current
Organic Chemistry
ISSN: 1385-2728
Current Organic
Chemistry
Volume 10, Number 14, September 2006
Contents
Synthetic Approaches for Total Chemical
Synthesis of Proteins and Protein-Like Macromolecules of Branched
Architecture Pp. 1727-1744
Serafim Papas, Constantinos Strongylis and Vassilios Tsikaris
[Abstract]
Non-conventional Glycosidic Linkages: Syntheses
and Structures of Thiooligosaccharides and Carbohydrates with
Three-bond Glycosidic Connections Pp. 1745-1770
László Szilágyi and Oscar Varela
[Abstract]
The Molecular Organization of Polymers of Cartilage
in Health and Disease Pp. 1771-1789
Jürgen Schiller, Beate Fuchs and Klaus Arnold
[Abstract]
Azide/Alkyne-"Click" Reactions: Applications
in Material Science and Organic Synthesis Pp. 1791-1815
Wolfgang H. Binder and Christian Kluger
[Abstract]
Secondary Amides as ortho-Directed Metallation
Groups for Arenes; a Useful Construction Way of the Polysubstituted
Aromatic and Heteroaromatic Systems Pp. 1817-1848
Jan Epsztajn, Andrzej Józ´wiak and Aleksandra
K. Szczes´niak
[Abstract]
Asymmetric Addition to Ketones: Enantioselective
Formation of Tertiary Alcohols Pp. 1849-1889
Celina García and Víctor S. Martín
[Abstract]
Abstracts
[Back to top]
Synthetic Approaches for Total Chemical Synthesis
of Proteins and Protein-Like Macromolecules of Branched Architecture
Serafim Papas, Constantinos Strongylis and Vassilios
Tsikaris
The progress achieved both in the solid and liquid phase
of the synthetic methodologies for peptides, permitted the
application of various chemistries for preparing totally synthetic
proteins and protein-like macromolecules of branched architecture.
Polypeptides with molecular masses in the 10-25 kDa range
have been successfully prepared using either the step by step
and fragment condensation or the chemoselective ligation methods.
Amide, thioether, disulfide, thioester, hydrazone, oxime and
thiazolidine linkages have been employed in such syntheses.
Fully active proteins or macromolecules mimicking particular
protein properties especially in immunology have been synthesized
in high purity and large quantities. The branched constructs
have found numerous applications in immunology due to their
contribution in overcoming the very low ability of short linear
peptides to react specifically with antibodies or to induce
an immune response. The advantages over almost all the other
methods of using synthetic carriers for developing potent
antigens and immunogens have placed this approach at the center
of extensive research activities. This review focuses on the
concept and synthetic strategies suitable for assembling proteins
or protein-like macromolecules of branched architecture with
application in protein function studies and immunology.
[Back to top]
Non-conventional Glycosidic Linkages: Syntheses
and Structures of Thiooligosaccharides and Carbohydrates with
Three-bond Glycosidic Connections
László Szilágyi and Oscar Varela
Thiooligosaccharides display inhibitory activity against
glycoside hydrolases and they constitute a valuable tool for
structural biology. The construction of the interglycosidic
linkage, in which the oxygen atom is replaced by sulfur, usually
involves one of the following reactions: i) nucleophilic displacement
of good leaving groups in a carbohydrate moiety by a sugar
thiol, ii) Michael and Michael-type additions of sugar thiols
to unsaturated acceptors, iii) ring-opening of aziridines
and oxiranes by thiosugars, iv) enzyme-catalyzed couplings
of thiosugar moieties. The application of these reactions
for the syntheses of thiooligosaccharides are surveyed, and
the biological activities of the resulting products briefly
described. Carbohydrate structures incorporating three-bond
glycosidic linkages with two heteroatoms are uncommon in Nature.
The –N–O– interglycosidic bond in the oligosaccharide
part of enediyne antibiotics is partly responsible for their
potent antitumor activities. The disulfide bond which plays
an essential role in proteins has recently been introduced
as an interglycosidic connecting motif. The sulfenamide functionality
is the sulfur analog of the hydroxylamine type glycosidic
linkages in calicheamicins. Novel glycosylation strategies
have recently been developed by taking advantage of unconventional,
three-bond glycosidic linkages to construct neoglycoproteins
and other glycoconjugates which are increasingly important
tools in glycobiology and drug discovery. To explore conformational
preferences and molecular flexibility in these structures
NMR spectroscopy, chiroptical methods and X-ray crystallography
are being used, supplemented by molecular modelling calculations.
The structural features will be briefly discussed with relevance
to biological interactions such as enzyme binding.
[Back to top]
The Molecular Organization of Polymers of Cartilage
in Health and Disease
Jürgen Schiller, Beate Fuchs and Klaus Arnold
Degenerative joint diseases (e.g. rheumatoid arthritis
or osteoarthritis) represent a major cause of disability and
early retirements in the industrialised countries. These diseases
affect primarily the cartilage of the larger joints and destroy
its macromolecular constituents.
Cartilage covers the ends of the bones acting as a weight
bearing, low friction, wear resistant tissue. It is known
that the composition of cartilage is crucial for its function
and forming the complex matrix network: This matrix consists
primarily of collagen and acidic polysaccharides (the glycosaminoglycans)
that form in combination with proteins the so-called proteoglycans.
This review is dedicated to the molecular organization of
cartilage and its components in health and disease with the
emphasis on the interactions between the individual polymeric
components. Therefore, some physico-chemical methods used
in cartilage research will be also discussed. The focus will
be on methods of nuclear magnetic resonance spectroscopy (NMR)
that allow a clear differentiation and characterization of
the components of cartilage.
It is one aim to prove that besides classical methods of biochemistry,
biophysical techniques are also useful to study cartilage
structure and function. Both, basic sciences and medical applications
will be considered. Finally, future prospects will be provided
how modern NMR techniques may help to assess the quality of
bioengineered cartilage.
[Back to top]
Azide/Alkyne-"Click" Reactions: Applications
in Material Science and Organic Synthesis
Wolfgang H. Binder and Christian Kluger
The fixation of ligands onto molecules, surfaces and materials
by use of reactions using a simple and unified chemistry is
among the everlasting desires of chemists. Besides the general
insensitivity with respect to the chemical structures of the
ligand, the completeness of the reaction as well as the insensitivity
from external reaction parameters (i.e.: solvents, ambient
temperature) is wished. The copper(I)-catalysed azide/alkyne
“click”-reaction (also termed Sharpless “click”-reaction,
a variation of the Huisgen 1,3-dipolar cycloaddition reaction
between terminal acetylenes and azides) is a recent re-discovery
of a reaction fulfilling these requirements. Extremely high
yields (usually above 95 %) are combined with a high tolerance
of functional groups and reactions running at moderate temperatures
(25°C – 70 °C). The present review assembles
recent literature for applications of these reactions in the
field of material science, in particular on surfaces, polymers,
and for the ligation of ligands to larger biomolecules, including
own publications in this field. Since this is an extremely
fast developing area, this review offers important knowledge
to the interested reader. A number of >64 references are
included.
[Back to top]
Secondary Amides as ortho-Directed Metallation
Groups for Arenes; a Useful Construction Way of the Polysubstituted
Aromatic and Heteroaromatic Systems
Jan Epsztajn, Andrzej Józ´wiak and Aleksandra
K. Szczes´niak
The lithiation electrophilic substitution sequence of
aromatic compounds has become very a common methodology for
ortho-introduction of a long list of substituents
in general. In particular, it was centered around the ortho-substitution
of aromatic carboxylic acids via their masked forms. Till
now, long list of reviews concerning tertiary amides or oxazolines
as directing groups has been referred. On the other hand,
secondary amides, even historically first masked function
of aromatic carboxylic acids, were discussed in much smaller
extent. In here, the scope of this methodology and the application
of the secondary amide function in organic synthesis is presented.
[Back to top]
Asymmetric Addition to Ketones: Enantioselective
Formation of Tertiary Alcohols
Celina García and Víctor S. Martín
The stereoselective formation of chiral tertiary alcohols
is of great importance for the synthesis of enantiomerically
pure natural products and pharmaceuticals. The simplest approach
for the preparation of chiral alcohols is the enantioselective
addition of organometallic reagents to carbonyl compounds.
Hundreds of catalysts promote nucleophilic additions of organometallic
compounds to aldehydes with high enantioselectivities. However,
the use of ketones as group acceptors under similar conditions
has proven much more challenging. The chemistry of catalytic
asymmetric additions to ketones is progressing, especially
since 1998. This review attempts to cover advances in this
field which have occurred between 1994-2004. Particular attention
is paid to chiral auxiliaries, reagents and catalysts used
for the addition to different kinds of ketones (aromatic and
aliphatic ketones, α,β-unsaturated
ketones, α-ketoesters)
as well as the enantiomeric excesses of the chiral tertiary
alcohols obtained for each case. In addition, a discussion
about the progress in the catalytic asymmetric addition to
ketoimines in order to generate enantiomerically enriched
tertiary amines will be presented. Finally, recent applications
of the asymmetric addition to ketones chemistry in the synthesis
of natural products and related compounds are reported.
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