8 research outputs found
Conformationally Armed 3,6-Tethered Glycosyl Donors: Synthesis, Conformation, Reactivity, and Selectivity
The reactivity and selectivity of
3,6-tethered glycosyl donors
have been studied using acceptors with different steric and electronic
characteristics. Eight (four anomeric pairs) 3,6-bridged-glycosyl
donors were synthesized in high yields from their common parent sugars.
The glycosylation properties were tested using at least three different
acceptors and several promoter systems. Thiophenyl 2,4-di-<i>O</i>-benzyl-3,6-<i>O</i>-(di-<i>tert</i>-butylsilylene)-α-d-glucopyranoside gave α/β
mixtures with standard NIS/TfOH mediated activation, whereas the corresponding
fluoride was found to be highly β-selective, when using SnCl<sub>2</sub>/AgB(C<sub>6</sub>F<sub>5</sub>)<sub>4</sub> as the promoter
system. Mannosyl donors were highly α-selective despite the
altered conformation. Galactosylations using NIS/TfOH were generally
α-selective, but more β-selective using the galactosyl
fluoride and depending on the acceptor used. Thiophenyl 2-azido-2-deoxy-4-<i>O</i>-benzyl-3,6-<i>O</i>-(di-<i>tert</i>-butylsilylene)-α-d-glucopyranoside was found to be
α-selective . The reactivity of the donors was investigated
using competition experiments, and some but not all were found to
be highly reactive. Generally it was found that the α-thioglycosides
were significantly more reactive than the β; this difference
in reactivity was not found for 3,6-anhydro-, armed-(benzylated),
or the classic super armed (silylated) donors. A mechanism supporting
the unusual observations has been suggested
Effect of 2‑<i>O</i>‑Benzoyl para-Substituents on Glycosylation Rates
From
a series of competition experiments, we have explored the
degree to which various para-substituents (CN, Br, H, OMe, pyrrolidino)
of a 2-<i>O</i>-benzoyl functionalized glucosyl donor of
the thioglycoside type affect the rate of glycosylation under <i>N</i>-iodosuccinimide/triflic acid activation. As expected,
electron-withdrawing groups were found to decrease the rate of glycosylation,
whereas electron-donating groups resulted in the opposite outcome,
underscoring the influence on the reaction rate exerted by a participating
group. On this basis, a Hammett linear free-energy relationship was
established (<i>R</i><sup>2</sup> = 0.979, ρ = 0.6),
offering fundamental insight into the magnitude of anchimeric assistance
in glycosylation chemistry
Rhamnosylation: Diastereoselectivity of Conformationally Armed Donors
The α/β-selectivity of super-armed rhamnosyl
donors
have been investigated in glycosylation reactions. The solvent was
found to have a minor influence, whereas temperature was crucial for
the diastereoselectivity. At very low temperature, a modest β-selectivity
could be obtained, and increasing temperature gave excellent α-selectivity.
The donors were highly reactive, and activation was observed at temperatures
as low as −107 °C. Different promoter systems and leaving
groups were investigated, and only activation with a heterogeneous
catalyst increased the amount of the β-anomer significantly.
By introducing an electron-withdrawing nonparticipating group, benzyl
sulfonyl, on 2-O, an increase in β-product was observed
3‑(Dimethylamino)-1-propylamine: A Cheap and Versatile Reagent for Removal of Byproducts in Carbohydrate Chemistry
Inexpensive
3-(dimethylamino)-1-propylamine (DMAPA) was found to
be effective in anomeric deacylation reactions giving 1-<i>O</i> deprotected sugars in high yield as precursors for the formation
of imidate glycosyl donors. DMAPA was also found to be useful for
removing excess reagents such as benzoyl chloride, tosyl chloride,
and 2,2,2-trifluoro-<i>N</i>-phenylacetimidoyl chloride.
The deacylation reaction could be conducted in moist THF and did not
require chromatographic purification since an acidic wash was sufficient
to remove excess reagent and the formed byproduct
Remote Electronic Effects by Ether Protecting Groups Fine-Tune Glycosyl Donor Reactivity
It was established that <i>para</i>-substituted benzyl
ether protecting groups affect the reactivity of glycosyl donors of
the thioglycoside type with the <i>N</i>-iodosuccinimide/triflic
acid promoter system. Having electron donating <i>p</i>-methoxybenzyl
ether (PMB) groups increased the reactivity of the donor in comparison
to having electron withdrawing <i>p</i>-chloro (PClB) or <i>p</i>-cyanobenzyl ether (PCNB) protecting groups, which decreased
the reactivity of the glycosyl donor relative to the parent benzyl
ether (Bn) protected glycosyl donor. These findings were used to perform
the first armed-disarmed coupling between two benzylated glucosyl
donors by tuning their reactivity. In addition, the present work describes
a highly efficient palladium catalyzed multiple cyanation and methoxylation
of <i>p</i>-chlorobenzyl protected thioglycosides. The results
of this paper regarding both the different electron withdrawing properties
of various benzyl ethers and the efficient and multiple protecting
group transformations are applicable in general organic chemistry
and not restricted to carbohydrate chemistry
<i>p</i>‑Chlorobenzyl Ether: A <i>p</i>‑Methoxybenzyl Ether in Disguise
In
the chemistry of polyfunctionalized organic compounds, protecting
groups that can undergo mild and selective cleavage while still being
stable during the entire synthetic sequence are often required. In
this work, we present a straightforward conversion of the robust <i>p</i>-chlorobenzyl ether into the more labile and well-described <i>p</i>-methoxybenzyl ether using palladium catalysis. This reaction
was demonstrated to be high yielding and compatible with a wide range
of functionalities, thereby providing a useful supplement to the conventional
ether protecting groups
β‑Selective Mannosylation with a 4,6-Silylene-Tethered Thiomannosyl Donor
Mannosylations
using the new conformationally restricted donor
phenyl 2,3-di-<i>O</i>-benzyl-4,6-<i>O</i>-(di-<i>tert</i>-butylsilylene)-1-thio-α-d-mannopyranoside
(<b>6</b>) have been found to be β-selective with a variety
of activation conditions. The simplest activation conditions were
NIS/TfOH, in which case it is proposed that the β-mannoside
is formed from β-selective glycosylation of the oxocarbenium
ion <b>25</b> in a <i>B</i><sub>2,5</sub> conformation
Superarming of Glycosyl Donors by Combined Neighboring and Conformational Effects
A novel glycosyl donor that combines the concepts of both conformational and electronic superarming has been synthesized. The reactivity and selectivity of the donor have been tested in competition experiments