The novel bridged nucleic-acid analogue 2',4'-BNA(NC) (2'-O,4'-C-aminomethylene bridged nucleic acid), containing a six-membered bridged structure with an N-O linkage, was designed and synthesized efficiently, demonstrating a one-pot intramolecular NC bond-forming key reaction to construct a perhydro-1,2-oxazine ring (11 and 12). Three monomers of 2',4'-BNA(NC) (2',4'-BNA(NC)[NH], [NMe], and [NBn]) were synthesized and incorporated into oligonucleotides, and their properties were investigated and compared with those of 2',4'-BNA (LNA)-modified oligonucleotides. Compared to 2',4'-BNA (LNA)-modified oligonucleotides, 2',4'-BNA(NC) congeners were found to possess: (i) equal or higher binding affinity against an RNA complement with excellent single-mismatch discriminating power, (ii) much better RNA selective binding, (iii) stronger and more sequence selective triplex-forming characters, and (iv) immensely higher nuclease resistance, even higher than the S(p)-phosphorthioate analogue. 2',4'-BNA(NC)-modified oligonucleotides with these excellent profiles show great promise for applications in antisense and antigene technologies.
The novel bridged nucleic-acid analogue 2',4'-BNA(NC) (2'-O,4'-C-aminomethylene bridged nucleic acid), containing a six-membered bridged structure with an N-O linkage, was designed and synthesized efficiently, demonstrating a one-pot intramolecular NC bond-forming key reaction to construct a perhydro-1,2-oxazine ring (11 and 12). Three monomers of 2',4'-BNA(NC) (2',4'-BNA(NC)[NH], [NMe], and [NBn]) were synthesized and incorporated into oligonucleotides, and their properties were investigated and compared with those of 2',4'-BNA (LNA)-modified oligonucleotides. Compared to 2',4'-BNA (LNA)-modified oligonucleotides, 2',4'-BNA(NC) congeners were found to possess: (i) equal or higher binding affinity against an RNA complement with excellent single-mismatch discriminating power, (ii) much better RNA selective binding, (iii) stronger and more sequence selective triplex-forming characters, and (iv) immensely higher nuclease resistance, even higher than the S(p)-phosphorthioate analogue. 2',4'-BNA(NC)-modified oligonucleotides with these excellent profiles show great promise for applications in antisense and antigene technologies.
“…The p -methoxybenzyl (PMB) ethers and their somewhat less acid sensitive congeners, the 2-naphthylmethyl (Nap) ethers, are staple protecting groups in organic synthesis, in general, and especially in oligosaccharide synthesis, owing to their facile oxidative cleavage with either dichlorodicyanoquinone (DDQ) or ceric ammonium nitrate (CAN). − Simple benzyl ethers are not inert to these oxidative cleavage conditions but typically react significantly more slowly, − enabling the highly selective cleavage of the PMB or Nap ethers in their presence. , By way of illustration, we have collated some recent examples of this type from our own laboratory, − along with an oxidative cyclization 17 and a pertinent literature example 1 in Table .…”
On exposure to dichlorodicyanoquinone in wet dichloromethane at room temperature, equatorial 4-O-benzyl ethers are removed with moderate selectivity in the presence of other benzyl ethers in glycopyranosides and glycothiopyranosides.
“…1.6 Total Synthesis of Erythronolide B: [Kochetkov, 1987] (Scheme 9) [17] Kochetkov's erythronolide synthesis is based on the construction of the secoacid from the C C C 6 (91) and C 9 -C 13 (93) segments, both of which are prepared from levoglucosan 88 through the C-methyl derivatives 89 and 92, respectively. 1.6 Total Synthesis of Erythronolide B: [Kochetkov, 1987] (Scheme 9) [17] Kochetkov's erythronolide synthesis is based on the construction of the secoacid from the C C C 6 (91) and C 9 -C 13 (93) segments, both of which are prepared from levoglucosan 88 through the C-methyl derivatives 89 and 92, respectively.…”
Section: The First Total Synthesis Of Erythronolide Bmentioning
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