Studies of the selective silylation of methyl α- and β-d-aldohexopyranosides: stability of the partially protected derivatives in polar solvents

Halmos, Thérèse; Montserret, Roland; Filippi, Jean Baptiste; Antonakis, Kostas

doi:10.1016/0008-6215(87)85005-x

Cited by 45 publications

(36 citation statements)

References 20 publications

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“…The indole nitrogen atom of indolocarbazole glucoside 1 was N ‐methylated as shown in Scheme . As expected, the yield of the persilylation in the first step was poor,10 but with some modifications the per‐ O ‐silylated derivative 2 a could be obtained in 33 % yield. The remainder of the material was a mixture of two tris‐silylated glycosides, which were inseparable.…”

Section: Resultssupporting

confidence: 72%

Indolocarbazole Glycosides in Inactive Conformations

et al. 2003

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Indolocarbazole glycosides related to rebeccamycin represent a promising category of antitumor agents targeting DNA and topoisomerase I. These drugs prefer to adopt a closed conformation with an intramolecular hydrogen bond between the indole NH group and the pyranose oxygen atom. Three pairs of indolocarbazole monoglycosides bearing an NH or an N-methyl indole moiety were synthesized and their biological properties investigated at the molecular and cellular level. Replacing the indole NH proton with a methyl group reduces DNA interaction and abolishes activity against DNA topoisomerase I. Surface plasmon resonance studies performed with a pair of water-soluble indolocarbazole glycosides and two hairpin oligonucleotides containing an [AT]4 or a [CG]4 sequence indicate that both the NH and the N-methyl derivative maintain a relatively high affinity for DNA (Keq = 2 - 6 x 10(5) M(-1)) but the incorporation of the methyl group restricts access to the DNA. The number of ligand binding sites (n) on the oligonucleotides is about twice as high for the NH compound compared to its N-methyl analogue. Modeling and 1H NMR studies demonstrate that addition of the N-methyl group drives a radical change in conformation in which the orientation of the aglycone relative to the beta-glucoside is reversed. The loss of the closed conformation by the N-methyl derivatives perturbs thir ability to access DNA binding sites and prevents the drug from inhibiting topoisomerase I. As a consequence, the NH compounds exhibit potent cytotoxicity against CEM leukemia cells with an IC50 value in the 1 microM range, whereas the N-methyl analogues are 10 to 100 times less cytotoxic. These studies offer circumstantial evidence supporting the importance of the closed conformation in the interaction of indolocarbazole glycosides with their molecular targets, DNA and topoisomerase I.

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Section: Resultssupporting

confidence: 72%

Indolocarbazole Glycosides in Inactive Conformations

et al. 2003

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“…However, changing the base to triethylamine completely inhibited rearrangements and TBS ether 24 was obtained in 91% yield. 30 DIBAL-H reduction at −78 °C followed by Seyferth-Gilbert homologation using the Ohira-Bestmann reagent 31 at 23 °C provided terminal alkyne 25 in 90% for the two-steps. Alkyne 25 was then alkylated to form alkynl ester 26 in quantitative yield.…”

Section: Resultsmentioning

confidence: 99%

Enantioselective total synthesis and structural assignment of callyspongiolide

2016

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We have elucidated the complete absolute configuration of callyspongiolide and unambiguously assigned its stereochemistry at the C-21 center through synthesis. Four stereoisomers of callyspongiolide were synthesized in a convergent and enantioselective manner. A late-stage Sonogashira coupling forges the diene-ynic side chain. Other notable reactions are Yonemitsu’s variation of the Yamaguchi macrolactonization to cyclize an alkynic seco acid, highly trans-selective Julia-Kocienski olefination, CBS reduction to set the C-21 stereocenter, and methyl cuprate addition to an unsaturated pyranone to install the C-5 methyl center.

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“…The regioselective silylation of secondary saccharide alcohols can also be achieved either taking advantage of the inherent difference of reactivity among the hydroxy functions [24–32] or exploiting the activation effect of boron complexes [33]. …”

Section: Introductionmentioning

confidence: 99%

Orthogonal protection of saccharide polyols through solvent-free one-pot sequences based on regioselective silylations

Traboni¹,

Bedini²,

Iadonisi³

2016

Beilstein J. Org. Chem.

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tert-Butyldimethylsilyl (TBDMS) and tert-butyldiphenylsilyl (TBDPS) are alcohol protecting groups widely employed in organic synthesis in view of their compatibility with a wide range of conditions. Their regioselective installation on polyols generally requires lengthy reactions and the use of high boiling solvents. In the first part of this paper we demonstrate that regioselective silylation of sugar polyols can be conducted in short times with the requisite silyl chloride and a very limited excess of pyridine (2–3 equivalents). Under these conditions, that can be regarded as solvent-free conditions in view of the insolubility of the polyol substrates, the reactions are faster than in most examples reported in the literature, and can even be further accelerated with a catalytic amount of tetrabutylammonium bromide (TBAB). The strategy proved also useful for either the selective TBDMS protection of secondary alcohols or the fast per-O-trimethylsilylation of saccharide polyols. In the second part of the paper the scope of the silylation approach was significantly extended with the development of unprecedented “one-pot” and “solvent-free” sequences allowing the regioselective silylation/alkylation (or the reverse sequence) of saccharide polyols in short times. The developed methodologies represent a very useful and experimentally simple tool for the straightforward access to saccharide building-blocks useful in organic synthesis.

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Studies of the selective silylation of methyl α- and β-d-aldohexopyranosides: stability of the partially protected derivatives in polar solvents

Cited by 45 publications

References 20 publications

Indolocarbazole Glycosides in Inactive Conformations

Indolocarbazole Glycosides in Inactive Conformations

Enantioselective total synthesis and structural assignment of callyspongiolide

Orthogonal protection of saccharide polyols through solvent-free one-pot sequences based on regioselective silylations

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