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.

Nucleoside syntheses, XXII1) Nucleoside synthesis with trimethylsilyl triflate and perchlorate as catalysts

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.

Nucleoside Syntheses, XXIII1) On the Mechanism of Nucleoside Synthesis

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.

Nucleoside syntheses, XXV1) A new simplified nucleoside synthesis

Lewis acid-mediated nucleophilic substitution reactions of substituted tetrahydropyran acetates reveal that the conformational preferences of six-membered-ring cations depend significantly upon the electronic nature of the substituent. Nucleophilic substitutions of C-3 and C-4 alkyl-substituted tetrahydropyran acetates proceeded via pseudoequatorially substituted oxocarbenium ions, as would be expected by consideration of steric effects. Substitutions of C-3 and C-4 alkoxy-substituted tetrahydropyran acetates, however, proceeded via pseudoaxially oriented oxocarbenium ions. The unusual selectivities controlled by the alkoxy groups were demonstrated for a range of other heteroatom substituents, including nitrogen, fluorine, chlorine, and bromine. It is believed that the pseudoaxial conformation is preferred in the ground state of the cation because of an electrostatic attraction between the cationic carbon center of the oxocarbenium ion and the heteroatom substituent. This analysis is supported by the observation that selectivity diminishes down the halogen series, which is inconsistent with electron donation as might be expected during anchimeric assistance. The C-2 heteroatom-substituted systems gave moderately high 1,2-cis selectivity, while small alkyl substituents showed no selectivity. Only in the case of the tert-butyl group at C-2 was high 1,2-trans selectivity observed. These studies reinforce the idea that ground-state conformational effects need to be considered along with steric approach considerations.

Stereochemistry of Nucleophilic Substitution Reactions Depending upon Substituent: Evidence for Electrostatic Stabilization of Pseudoaxial Conformers of Oxocarbenium Ions by Heteroatom Substituents

The faithful recognition of the interstrand hydrogen bonds between complementary nucleobases forms the foundation of the genetic code. The ability to replicate DNA containing a stable third base pair would allow for an expansion of the information content of DNA by supplementing the existing two base pairs of the genetic alphabet with a third. We report the optimization of unnatural nucleobases whose pairing in duplex DNA is based on interbase hydrophobic interactions. We show that the stability and selectivity of such unnatural base pairs may be comparable to, or even exceed, that of native pairs. We also demonstrate that several unnatural base pairs are incorporated into DNA by Klenow fragment of Escherichia coli DNA polymerase I with an efficiency equivalent to that of native DNA synthesis. Moreover, the unnatural bases are orthogonal to the native bases, with correct pairing being favored by at least an order of magnitude relative to mispairing.

Niedballa U

Papers

A general synthesis of N-glycosides. II. Synthesis of 6-methyluridines.