Nucleoside syntheses, XXII1) Nucleoside synthesis with trimethylsilyl triflate and perchlorate as catalysts
TL;DR: The Lewis acids (CH3)3SiOSO2CF3 (3), CH3 5S iOSO2C4F9 (6), and CH3 3SiClO4 (4) are highly selective and efficient Friedel-Crafts catalysts for nucleoside formation form silylated heterocycles and peracylated sugars as discussed by the authors.
Abstract: The novel Lewis acids (CH3)3SiOSO2CF3 (3), (CH3)5SiOSO2C4F9 (6), and (CH3)3SiClO4 (4) are highly selective and efficient Friedel-Crafts catalysts for nucleoside formation form silylated heterocycles and peracylated sugars as well as for rearrangements of persilylated protected nucleosides. With basic silylated heterocycles these new catalysts give much higher yields of the natural N-1-nucleosides than with SnCl4.
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TL;DR: Emphasis is placed on glycoside and saccharide formation by 1-O-alkylation, on the trichloroacetimidate method, and on activation through the formation of glycosylsulfonium salts and Glycosyl fluorides.
Abstract: Glycoproteins, glycolipids, and glycophospholipids (glycoconjugates) are components of membranes. The oligosaccharide residue is responsible for intercellular recognition and interaction; it acts as a receptor for proteins, hormones, and viruses and governs immune reactions. These significant activities have stimulated interest in oligosaccharides and glycoconjugates. With their help it should be possible to clarify the molecular basis of these phenomena and to derive new principles of physiological activity. Major advances in the synthesis of oligosaccharides have been made by the use of the Koenigs-Knorr method, in which glycosyl halides in the presence of heavy-metal salts are employed to transfer the glycosyl group to nucleophiles. The disadvantages of this procedure have led to an intensive search for new methods. Such methods will be discussed in this article. Emphasis is placed on glycoside and saccharide formation by 1-O-alkylation, on the trichloroacetimidate method, and on activation through the formation of glycosylsulfonium salts and glycosyl fluorides.
1,185 citations
TL;DR: Studies of mis-matched sequences show that LNA obey the Watson-Crick base pairing rules with generally improved selectivities compared to the corresponding unmodified reference strands.
1,155 citations
TL;DR: A novel class of nucleic acid analogues, termed LNA (locked nucleic acids), is introduced following the Watson–Crick base pairing rules, which forms duplexes with complementary DNA and RNA with remarkably increased thermal stabilities and generally improved selectivities.
828 citations
TL;DR: This review which is the second in this series summarises the most common synthetic routes as applied to the preparation of many modern pharmaceutical compounds categorised as containing a six-membered heterocyclic ring.
Abstract: This review which is the second in this series summarises the most common synthetic routes as applied to the preparation of many modern pharmaceutical compounds categorised as containing a six-membered heterocyclic ring. The reported examples are based on the top retailing drug molecules combining synthetic information from both scientific journals and the wider patent literature. It is hoped that this compilation, in combination with the previously published review on five-membered rings, will form a comprehensive foundation and reference source for individuals interested in medicinal, synthetic and preparative chemistry.
563 citations
TL;DR: Glycoproteine, Glycolipide and Glycophospholipide (=Glycokonjugate) sind Bestandteile von Membranen.
Abstract: Glycoproteine, Glycolipide und Glycophospholipide (=Glycokonjugate) sind Bestandteile von Membranen. Dabei ist der oligosaccharidische Teil fur Zell-Zell-Erkennung und -Wechselwirkung zustandig; er fungiert als Rezeptor fur Proteine, Hormone und Viren und determiniert Immunreaktionen. Diese Bedeutung hat das Interesse an Oligosacchariden und Glycokonjugaten stimuliert. Mit ihnen sollte es gelingen, die molekulare Basis dieser Phanomene aufzuklaren und neue physiologische Wirkprinzipien abzuleiten. Grose Fortschritte der Oligosaccharidsynthese sind mit der Koenigs-Knorr-Methode erzielt worden, bei der Halogenosen in Gegenwart von Schwermetallsalzen zur Glycosylubertragung auf Nucleophile dienen. Die Nachteile dieses Verfahrens haben zu einer intensiven Suche nach neuen Methoden gefuhrt. In diesem Beitrag werden solche Methoden diskutiert. Dabei ist insbesondere auf die Glycosid- und Saccharidbildung durch 1-O-Alkylierung, auf die Trichloracetimidat-Methode und auf die Aktivierung uber Glycosylsulfoniumsalze und Glycosylfluoride hinzuweisen.
411 citations
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394 citations
353 citations
TL;DR: In this paper, the authors discuss the probable mechanism of nucleoside synthesis and the factors which influence course and yield of the nucleosid synthesis process, including the formation of the electrophilic sugar cation.
Abstract: During the silyl-Hilbert-Johnson nucleoside synthesis with Friedel-Crafts catalysts three processes occur simultanously:
A)
The formation of the electrophilic sugar cation.
B)
The σ-complex formation between th silylated base and the Friedel-Crafts catalyst and finally.
C)
The reaction of the electrophilic sugar cation with the silylated base to the nucleoside. Mode and rate of σ-complex formation between the silylated base and the Friedel-Crafts catalysts were monitored by 13C-NMR. The probable mechanism of nucleoside synthesis and the factors which influence course and yield of nucleoside synthesis are discussed.
Nucleosid-Synthesen, XXIII1) Uber den Mechanismus der Nucleosid-Synthese
In der Silyl-Hilbert-Johnson-Reaktion geschehen drei Prozesse gleichzeitig:
A)
Die Bildung des elektrophilen Zucker-Kations.
B)
Die σ-Komplex-Bildung zwischen der silylierten Base und dem Friedel-Crafts-Katalysator.
C)
Die Reaktion des elektrophilen Zucker-Kations mit der silylierten Base zum Nucleosid. Art und Geschwindigkeit der σ-Komplex-Bildung zwischen der Silylierten Base und den Friedel-Crafts-Katalysatoren wurden mit Hilfe der 13C-NMR verfolgt. Der wahrscheinliche Mechanismus der Nucleosid-Synthese und die Faktoren, die Verlauf und Ausbeute der Nucleosid-Synthese beeinflussen, werden diskutiert.
264 citations
TL;DR: The Friedel-Crafts catalyzed silyl-Hilbert-Johnson nucleoside synthesis can be combined to a simple one-step/one-pot reaction which generally affords nucleosides in high yields as mentioned in this paper.
Abstract: The several steps of the Friedel-Crafts catalyzed silyl-Hilbert-Johnson nucleoside synthesis - silylation of the heterocyclic base, silylation of the perfluorosulfonic acids or its salts (if SnCl4 is not used as catalyst) and finally the nucleoside synthesis itself - can be combined to a simple one-step/one-pot reaction which generally affords nucleosides in high yields.
247 citations