Carbohydrate-DNA Conjugation Enabled by Glycosyl Radicals Generated from Glycosyl Sulfinates

Zeng, Hongxin; Li, Yanjing; Zhang, Yaoxin; Xu, Shuo; Wang, Yingwei; Niu, Dawen

doi:10.26434/chemrxiv-2023-z0mqc-v2

Cited by 3 publications

(3 citation statements)

References 5 publications

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“…These features collectively render transition-metal-free arylation a preferable method, particularly in the realm of drug discovery. Therefore, our interest was piqued in exploring the transition-metal-free glycosyl sulfonation 8 of easily accessible diaryliodonium salts employing sodium glycosyl sulfinate, 9 which was firstly reported by Niu's group recently.…”

Section: Introductionmentioning

confidence: 99%

Transition-metal-free glycosyl sulfonation of diaryliodonium salts with sodium glycosyl sulfinate: an efficient approach to access glycosyl aryl sulfones

Luo,

Chen,

Ding

et al. 2024

New J. Chem.

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Section: Introductionmentioning

confidence: 99%

Transition-metal-free glycosyl sulfonation of diaryliodonium salts with sodium glycosyl sulfinate: an efficient approach to access glycosyl aryl sulfones

Luo,

Chen,

Ding

et al. 2024

New J. Chem.

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“…Given their structural diversity and biological activity, incorporating sugar moieties onto DNA tags to create sugar-containing DELs holds significant promise for the R&D of carbohydrate-based drug discovery and chemical biology research 3 . However, due to the complexity of sugar molecules and the scarcity of DNA-compatible glycosylations, chemical reactions linking sugars with DNA tags are rare [59][60][61][62] . Encouraged by the successful results and considering the excellent reactivity and stability of the efficient C1-glycal boronates here developed, we integrated DEL technology with our highly efficient Pd-catalyzed Suzuki-Miyaura coupling methods to synthesize carbohydrate-DNA conjugates (Fig.…”

Section: Applicationmentioning

confidence: 99%

Palladium-catalyzed Suzuki-Miyaura cross-couplings of stable glycal boronates for robust synthesis of C-1 glycals

Chen,

Han,

et al. 2024

Nat Commun

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C-1 Glycals serve as pivotal intermediates in synthesizing diverse C-glycosyl compounds and natural products, necessitating the development of concise, efficient and user-friendly methods to obtain C-1 glycosides is essential. The Suzuki-Miyaura cross-coupling of glycal boronates is notable for its reliability and non-toxic nature, but glycal donor stability remains a challenge. Herein, we achieve a significant breakthrough by developing stable glycal boronates, effectively overcoming the stability issue in glycal-based Suzuki–Miyaura coupling. Leveraging the balanced reactivity and stability of our glycal boronates, we establish a robust palladium-catalyzed glycal-based Suzuki-Miyaura reaction, facilitating the formation of various C(sp2)-C(sp), C(sp2)-C(sp2), and C(sp2)-C(sp3) bonds under mild conditions. Notably, we expand upon this achievement by developing the DNA-compatible glycal-based cross-coupling reaction to synthesize various glycal-DNA conjugates. With its excellent reaction reactivity, stability, generality, and ease of handling, the method holds promise for widespread appication in the preparation of C-glycosyl compounds and natural products.

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“…In 2023, we demonstrated this point in the synthesis of carbohydrate−DNA conjugates using glycosyl sulfinates as glycosyl donors (Scheme 12). 51 Our method of glycosylation could proceed in a DMSO/water system buffered with KH 2 PO 4 , at ca. 0.3 mM concentration of DNA tags on a 10 nmol scale (Scheme 12).…”

Section: Glycosyl Sulfinates In Making Carbohydrate−dna Conjugatesmentioning

confidence: 99%

Radical Pathway Glycosylation Empowered by Bench-Stable Glycosyl Donors

Shang,

Niu

2023

Acc. Chem. Res.

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Conspectus The study of carbohydrates has emerged as a crucial research area in various disciplines due to their pivotal roles in cellular processes. To facilitate in-depth exploration of their biological functions, chemical glycosylation reactions that allow facile access of glycoconjugates to a broad research community are highly needed. In classical glycosylation reactions, a glycosyl donor is activated by an acid to generate a reactive electrophilic intermediate, which subsequently forms a glycosidic bond upon reaction with a nucleophilic acceptor. Such an ionic pathway glycosylation has been the mainstay technique for glycoconjugate synthesis and allowed the synthesis of numerous intricate structures. Nevertheless, limitations still exist. For instance, when labile glycosyl donors or harsh activating conditions are required, these methods show limited tolerance to hydroxyl groups that are abundant on sugar rings. In addition, achieving good stereocontrol represents another longstanding obstacle. In recent years, new modes of donor activation have been sought to tackle the above challenges. We noted that glycosylation methods passing through the intermediacy of glycosyl radicals via a cascade of single-electron transfer steps possess significant but underexplored potential. Progress in this area has been slow due in large part to a dearth of handy methods to generate and maneuver glycosyl radicals. Most existing methods call for either forcing conditions or unstable/inconvenient starting materials. In order to better exploit the power of the radical pathway glycosylation, we have developed a range of glycosyl donorsnamely, glycosyl sulfoxides, glycosyl sulfones, and glycosyl sulfinatesthat are bench stable and can be readily prepared from simple starting materials. These donors can be activated to form glycosyl radicals under mild conditions. Enabled by the use of these donors, we have developed a series of glycosylation methods that could be used for making O-, S-, or C-glycosides, some of which were previously difficult to access. In many cases, no protecting group on glycosyl donors is required. As an illustration of their potential utility, our methods have been adopted in the preparation of sugar–drug conjugates, sugar–DNA conjugates, glycopeptides, and even glycoproteins. While in most cases the intrinsic reactivity of glycosyl radical intermediates can be explored to access axially configured products, some of the methods also allow the utilization of external, delicate reagents, or catalysts to override such innate preference and achieve catalyst-controlled stereoselectivity. We believe that radical pathway glycosylation has enormous potential and can inspire the development of novel methods for glycoside synthesis. In this Account, we highlight the design principles for the development of our glycosyl donors, summarize our recent advancements in radical pathway glycosylation enabled by their use, and provide an outlook on the future directions of this field.

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Carbohydrate-DNA Conjugation Enabled by Glycosyl Radicals Generated from Glycosyl Sulfinates

Cited by 3 publications

References 5 publications

Transition-metal-free glycosyl sulfonation of diaryliodonium salts with sodium glycosyl sulfinate: an efficient approach to access glycosyl aryl sulfones

Transition-metal-free glycosyl sulfonation of diaryliodonium salts with sodium glycosyl sulfinate: an efficient approach to access glycosyl aryl sulfones

Palladium-catalyzed Suzuki-Miyaura cross-couplings of stable glycal boronates for robust synthesis of C-1 glycals

Radical Pathway Glycosylation Empowered by Bench-Stable Glycosyl Donors

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