Two‐Step Functionalization of Oligosaccharides Using Glycosyl Iodide and Trimethylene Oxide and Its Applications to Multivalent Glycoconjugates

Hsieh, Hsiao‐Wu; Davis, Ryan A.; Hoch, Jessica A.; Gervay‐Hague, Jacquelyn

doi:10.1002/chem.201400024

Cited by 15 publications

(13 citation statements)

References 89 publications

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“…converted per ‐O‐acetylated iso ‐globotrihexose to a glycosyl iodide and coupled it with stannylceramide in the presence of TBAI . In 2014, Gervay‐Hague and co‐workers activated glycosyl iodides with I 2 to their corresponding reactive glycosyl donors and proceeded towards glycosylation to yield various glycoconjugates . Though there has been much study of glycosylations with typically benzyl‐protected glycosyl iodides, Stachulski and co‐workers presented a detailed study of glycosylation reaction of ‘disarmed’ glycosyl iodides with various types of alcohols promoted by the NIS–I 2 –TMSOTf system .…”

Section: Glycosylationsmentioning

confidence: 99%

Chemical O‐Glycosylations: An Overview

2016

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The development of glycobiology relies on the sources of particular oligosaccharides in their purest forms. As the isolation of the oligosaccharide structures from natural sources is not a reliable option for providing samples with homogeneity, chemical means become pertinent. The growing demand for diverse oligosaccharide structures has prompted the advancement of chemical strategies to stitch sugar molecules with precise stereo‐ and regioselectivity through the formation of glycosidic bonds. This Review will focus on the key developments towards chemical O‐glycosylations in the current century. Synthesis of novel glycosyl donors and acceptors and their unique activation for successful glycosylation are discussed. This Review concludes with a summary of recent developments and comments on future prospects.

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Section: Glycosylationsmentioning

confidence: 99%

Chemical O‐Glycosylations: An Overview

2016

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“…Conditions have also been established for cyclic ether addition to disarmed glycosyl donors, in which case I 2 activation and microwave conditions are required (Table 4). 41 This protocol is especially useful because it works well for mono-, di-, and trisaccharides and the resulting iodoalkyl glycoconjugate can be easily substituted with other functional groups.…”

Section: Accounts Of Chemical Researchmentioning

confidence: 99%

Taming the Reactivity of Glycosyl Iodides To Achieve Stereoselective Glycosidation

Gervay‐Hague

2015

Acc. Chem. Res.

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CONSPECTUS: Although glycosyl iodides have been known for more than 100 years, it was not until the 21st century that their full potential began to be harnessed for complex glycoconjugate synthesis. Mechanistic studies in the late 1990s probed glycosyl iodide formation by NMR spectroscopy and revealed important reactivity features embedded in protecting-group stereoelectronics. Differentially protected sugars having an anomeric acetate were reacted with trimethylsilyl iodide (TMSI) to generate the glycosyl iodides. In the absence of C-2 participation, generation of the glycosyl iodide proceeded by inversion of the starting anomeric acetate stereochemistry. Once formed, the glycosyl iodide readily underwent in situ anomerization, and in the presence of excess iodide, equilibrium concentrations of α-and β-iodides were established. Reactivity profiles depended upon the identity of the sugar and the protecting groups adorning it. Consistent with the modern idea of disarmed versus armed sugars, ester protecting groups diminished the reactivity of glycosyl iodides and ether protecting groups enhanced the reactivity. Thus, acetylated sugars were slower to form the iodide and anomerize than their benzylated analogues, and these disarmed glycosyl iodides could be isolated and purified, whereas armed ether-protected iodides could only be generated and reacted in situ. All other things being equal, the β-iodide was orders of magnitude more reactive than the thermodynamically more stable α-iodide, consistent with the idea of in situ anomerization introduced by Lemieux in the mid-20th century. Glycosyl iodides are far more reactive than the corresponding bromides, and with the increased reactivity comes increased stereocontrol, particularly when forming α-linked linear and branched oligosaccharides. Reactions with per-O-silylated glycosyl iodides are especially useful for the synthesis of α-linked glycoconjugates. Silyl ether protecting groups make the glycosyl iodide so reactive that even highly functionalized aglycon acceptors add. Following the coupling event, the TMS ethers are readily removed by methanolysis, and since all of the byproducts are volatile, multiple reactions can be performed in a single reaction vessel without isolation of intermediates. In this fashion, per-O-TMS monosaccharides can be converted to biologically relevant α-linked glycolipids in one pot. The stereochemical outcome of these reactions can also be switched to β-glycoside formation by addition of silver to chelate the iodide, thus favoring S N 2 displacement of the α-iodide. While iodides derived from benzyl and silyl ether-protected oligosaccharides are susceptible to interglycosidic bond cleavage when treated with TMSI, the introduction of a single acetate protecting group prevents this unwanted side reaction. Partial acetylation of armed glycosyl iodides also attenuates HI elimination side reactions. Conversely, fully acetylated glycosyl iodides are deactivated and require metal catalysis in order for glycosidation to occur. Recent findings...

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“…Although methodologies exist to provide 1,2- trans linkages with great confidence, 1–3 procedures for achieving 1,2- cis glycosylations are limited. 4 As early as 1975, Lemieux and co-workers reported efficient routes to 1,2- cis glycosides using in situ anomerization of anomeric bromides, Figure 1.…”

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confidence: 99%

“…However, unlike monosaccharide donors, per- O -silyl oligosaccharides cannot be used as donors in glycosyl iodide glycosylation because ether protecting groups also render the interglycosidic bond susceptible to cleavage into smaller units when treated with TMSI. 2,3,22 In stark contrast, ester protecting groups are referred to as ‘disarming’ due to inductive effects; and while they stabilize interglycosidic linkages toward degradation, ester-protected glycosyl iodides are considerably less reactive than their ether protected counterparts. Moreover, if the ester is proximal to the anomeric center, for example, at the C-2 position, it typically guides glycosylation toward 1,2- trans linkages (Fig.…”

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confidence: 99%

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Synthesis of cholesteryl-α-d-lactoside via generation and trapping of a stable β-lactosyl iodide

Davis

Fettinger

Gervay‐Hague

2015

Tetrahedron Letters

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The generation of β-lactosyl iodide was carried out under non-in situ-anomerization, metal free conditions by reacting commercially available β-per-O-acetylated lactose with trimethylsilyl iodide (TMSI). The β-iodide was surprisingly stable as evidenced by NMR spectroscopy. Introduction of octanol or cholesterol under microwave conditions gave high yields of α-linked glycoconjugates. Careful analysis of the reaction products and mechanistic considerations suggest an acid catalyzed rearrangement that provides α-linked glycosylation products with a free C2-hydroxyl. Accessibility to these compounds may further advance glycolipidomic profiling of immune modulating bacterial derived-glycans.

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Two‐Step Functionalization of Oligosaccharides Using Glycosyl Iodide and Trimethylene Oxide and Its Applications to Multivalent Glycoconjugates

Cited by 15 publications

References 89 publications

Chemical O‐Glycosylations: An Overview

Chemical O‐Glycosylations: An Overview

Taming the Reactivity of Glycosyl Iodides To Achieve Stereoselective Glycosidation

Synthesis of cholesteryl-α-d-lactoside via generation and trapping of a stable β-lactosyl iodide

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