H-bond-mediated Aglycone Delivery Research Articles

Cooperatively Catalyzed Activation of Thioglycosides That Bypasses Intermediacy of Glycosyl Halides.

Reported herein is the development of a novel method for activating thioglycosides without a glycosyl halide intermediate. This has been achieved through the use of a silver salt coupled with an acid additive and molecular iodine. The enhanced stereocontrol was achieved via the H-bond mediated aglycone delivery (HAD) method, and the extended trisaccharide synthesis was achieved via iteration of deprotection and glycosylation steps.

Synthesis and glycosidation of building blocks of D-altrosamine.

Presented herein is a streamlined synthesis of building blocks of a rare sugar D-altrosamine. Also investigated was the glycosylation of different glycosyl acceptors with differentially protected altrosamine donors. High facial stereoselectivity was achieved with 3-O-picoloyl donors and reactive glycosyl acceptors via the H-bond-mediated aglycone delivery (HAD) pathway. In contrast, glycosidations of the altrosamine donor equipped with the 3-O-benzoyl group were poorly stereoselective.

Direct Synthesis of Glycans Containing Challenging ManNAcA Residues.

A method for direct, highly stereoselective synthesis of glycans containing β-linked d-mannosaminuronic acid (ManNAcA) residues is reported herein, among which is the capsular polysaccharide of Staphylococcus aureus type 8. Previous chemical syntheses of this glycan relied on indirect methods comprising glucosylation followed by a multistep epimerization and oxidation sequence. The high β-stereocontrol with direct glycosidation of 3-O-picoloylated ManNAcA donors was achieved using the H-bond-mediated aglycone delivery (HAD) reaction. A method to achieve complete α-ManNAcA stereoselectivity with 3-O-benzoylated donors is also reported.

A versatile approach to the synthesis of glycans containing mannuronic acid residues.

Reported herein is a new method for a highly effective synthesis of β-glycosides from mannuronic acid donors equipped with the 3-O-picoloyl group. The stereocontrol of glycosylations was achieved by means of the H-bond-mediated aglycone delivery (HAD). The method was utilized for the synthesis of a tetrasaccharide linked viaβ-(1 → 3)-mannuronic linkages. We have also investigated 3,6-lactonized glycosyl donors that provided moderate to high β-manno stereoselectivity in glycosylations. A method to achieve complete α-manno stereoselectivity with mannuronic acid donors equipped with 3-O-benzoyl group is also reported.

Synthesis of β-Glucosides with 3-O-Picoloyl-Protected Glycosyl Donors in the Presence of Excess Triflic Acid: A Mechanistic Study.

Our previous study showed that picoloylated donors are capable of providing excellent facial stereoselectivity through the H-bond-mediated aglycone delivery (HAD) pathway. Presented herein is a detailed mechanistic study of stereoselective glycosylation with 3-O-picoloylated glucosyl donors. While reactions of glycosyl donors equipped with the 3-O-benzoyl group are typically non-stereoselective because these reactions proceed via the oxacarbenium intermediate, 3-O-picoloylated donors are capable of providing enhanced, but somewhat relaxed, β-stereoselectivity by the HAD pathway. In an attempt to refine this reaction, we noticed that glycosylations are highly β-stereoselective in the presence of NIS and stoichiometric TfOH. The HAD pathway is highly unlikely because the picoloyl nitrogen is protonated under these reaction conditions. The protonation and glycosylation were studied by low-temperature NMR, and the intermediacy of the glycosyl triflate has been observed. This article is dedicated to broadening the scope of this reaction in application to a variety of substrates and targets.

Investigation of the H-bond-mediated aglycone delivery reaction in application to the synthesis of β-glucosides

In an attempt to refine the H-bond-mediated Aglycone Delivery (HAD) glycosylation reaction reported herein is the synthesis of β-glucosides using an ethylthio glucoside donor equipped with the remote 6-O-picoloyl substituent. Upon examining various aliphatic, aromatic, and carbohydrate acceptors, it was determined that both electronic and steric factors may greatly affect the stereoselectivity of the HAD reaction with this donor.

6-O-Picolinyl and 6-O-Picoloyl Building Blocks As Glycosyl Donors with Switchable Stereoselectivity.

Remote 6-O-picolinyl or 6-O-picoloyl substituents often provide high β-selectivity due to H-bond-mediated aglycone delivery (HAD). Herein it has been demonstrated that if the nitrogen atom of the 6-O-picolinyl or picoloyl moiety is temporarily blocked by coordination to a metal center (Pd), it cannot engage in HAD-mediated β-glycosylation. Hence, the stereoselectivity of 6-O-picolinyl/picoloyl-assisted glycosylations can be "switched" to α-selectivity.

Halobenzoyl groups in glycosylation: effect on stereoselectivity and reactivity of glycosyl donors

Described herein is the synthesis and evaluation of a series of glycosyl donors equipped with halobenzoyl substituents at O(4) and O(6) to study their properties in glycosylations. Among possible effects that may include carbonyl participation or H-bond mediated aglycone delivery, our results indicate that halobenzoyls act via a different mode.