Total Synthesis of C-α-Mannosyl Tryptophan via Palladium-Catalyzed C–H Glycosylation

Wang, Quanquan; Fu, Yingjuan; Zhu, Wanjun; An, Shuang; Zhou, Qian-Yi; Zhu, Shou‐Fei; He, Gang; Liu, Peng; Chen, Gong

doi:10.31635/ccschem.020.202000380

Cited by 57 publications

(25 citation statements)

References 40 publications

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“…Thus far, with the complex peptide and densely functionalized carbohydrate substrate, controlling both the stereocenters of the two coupling partners in the reaction is quite challenging. To date, the established C ‐glycosylation of glycine was either lack of stereocontrols [12] or poorly tolerated with peptide substrates [8c, 12] …”

Section: Methodsmentioning

confidence: 99%

Visible‐Light‐Promoted Stereoselective C(sp³)−H Glycosylation for the Synthesis of C‐Glycoamino Acids and C‐Glycopeptides

Wang

et al. 2022

Angewandte Chemie

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The glycosylative modification of peptides could improve the pharmacological properties of peptide drugs and deliver them efficiently to the target sites. Compared with O‐/N‐glycosides, C‐glycosides exhibit more metabolic stability. We here disclose the first example of visible‐light‐promoted and Cu‐catalyzed stereoselective C‐glycosylation. The mild reaction conditions are compatible with various carbohydrate substrates, as demonstrated with a series of monosaccharides and a disaccharide, and are amenable to the synthesis of a wide variety of C‐glycoamino acids and C‐glycopeptidomimetics with good yields and excellent stereoselectivities. The dual‐functional photocatalyst formed in situ via coordination of the glycine derivative and the chiral phosphine Cu complex could not only catalyze the photoredox process but also control the stereoselectivity of the glycosylation reaction.

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Section: Methodsmentioning

confidence: 99%

Visible‐Light‐Promoted Stereoselective C(sp³)−H Glycosylation for the Synthesis of C‐Glycoamino Acids and C‐Glycopeptides

Wang

et al. 2022

Angewandte Chemie

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“…Recently, a Pd(OAc) 2 catalyzed C–H activation strategy for C -Man-Trp synthesis was reported ( Scheme 4 ) [ 38 ]. The amide group and quinoline worked as bidentate ligands to the Pd catalyst.…”

Section: Structural and Synthetic Biology Of Protein C -Mannosylation And C -Man-trpmentioning

confidence: 99%

Protein C-Mannosylation and C-Mannosyl Tryptophan in Chemical Biology and Medicine

et al. 2021

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C-Mannosylation is a post-translational modification of proteins in the endoplasmic reticulum. Monomeric α-mannose is attached to specific Trp residues at the first Trp in the Trp-x-x-Trp/Cys (W-x-x-W/C) motif of substrate proteins, by the action of C-mannosyltransferases, DPY19-related gene products. The acceptor substrate proteins are included in the thrombospondin type I repeat (TSR) superfamily, cytokine receptor type I family, and others. Previous studies demonstrated that C-mannosylation plays critical roles in the folding, sorting, and/or secretion of substrate proteins. A C-mannosylation-defective gene mutation was identified in humans as the disease-associated variant affecting a C-mannosylation motif of W-x-x-W of ADAMTSL1, which suggests the involvement of defects in protein C-mannosylation in human diseases such as developmental glaucoma, myopia, and/or retinal defects. On the other hand, monomeric C-mannosyl Trp (C-Man-Trp), a deduced degradation product of C-mannosylated proteins, occurs in cells and extracellular fluids. Several studies showed that the level of C-Man-Trp is upregulated in blood of patients with renal dysfunction, suggesting that the metabolism of C-Man-Trp may be involved in human kidney diseases. Together, protein C-mannosylation is considered to play important roles in the biosynthesis and functions of substrate proteins, and the altered regulation of protein C-manosylation may be involved in the pathophysiology of human diseases. In this review, we consider the biochemical and biomedical knowledge of protein C-mannosylation and C-Man-Trp, and introduce recent studies concerning their significance in biology and medicine.

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“…A number of approaches to the synthesis of Trp(Man) 1 have been described (Scheme A). − Isobe and co-workers performed a Larock synthesis to obtain α- d -mannosyl indole 2 and a regio- and stereoselective alkylation with aziridine 3 to access 1 (Scheme A-i), , while Ito and co-workers accessed 1 via a stereocontrolled ring opening of epoxide 4 with lithiated tryptophanol derivative 5 (Scheme A-ii). , These strategies are too long and low-yielding to provide the gram quantities of 1 required for automated SPPS. A more recent approach by Chen and co-workers used an isoquinoline-1-carboxamide auxiliary on tryptophan 6 to direct a Pd-mediated C–H activation and glycosylation at C-2 using glycosyl chloride 7 (Scheme A-iii) . The limitation of this approach is that the isoquinoline directing group requires strong acid for removal and, as reported here for the first time, this results in anomerization of 1 to the β-anomer 1β (Scheme A).…”

Section: Introductionmentioning

confidence: 99%

Synthesis of C-Mannosylated Glycopeptides Enabled by Ni-Catalyzed Photoreductive Cross-Coupling Reactions

Mao

Shah

et al. 2021

J. Am. Chem. Soc.

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The biological functions of tryptophan C-mannosylation are poorly understood, in part, due to a dearth of methods for preparing pure glycopeptides and glycoproteins with this modification. To address this issue, efficient and scalable methods are required for installing this protein modification. Here, we describe unique Ni-catalyzed cross-coupling conditions that utilize photocatalysis or a Hantzsch ester photoreductant to couple glycosyl halides with (hetero)aryl bromides, thereby enabling the α-C-mannosylation of 2-bromo-tryptophan, peptides thereof, and (hetero)aryl bromides more generally. We also report that 2-(α-Dmannopyranosyl)-L-tryptophan undergoes facile anomerization in the presence of acid: something that must be considered when preparing and handling peptides with this modification. These developments enabled the first automated solid-phase peptide syntheses of C-mannosylated glycopeptides, which we used to map the epitope of an antibody, as well as providing the first verified synthesis of Carmo-HrTH-I, a C-mannosylated insect hormone. To complement this approach, we also performed late-stage tryptophan C-mannosylation on a diverse array of peptides, demonstrating the broad scope and utility of this methodology for preparing glycopeptides.

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Total Synthesis of C-α-Mannosyl Tryptophan via Palladium-Catalyzed C–H Glycosylation

Cited by 57 publications

References 40 publications

Visible‐Light‐Promoted Stereoselective C(sp³)−H Glycosylation for the Synthesis of C‐Glycoamino Acids and C‐Glycopeptides

Visible‐Light‐Promoted Stereoselective C(sp³)−H Glycosylation for the Synthesis of C‐Glycoamino Acids and C‐Glycopeptides

Protein C-Mannosylation and C-Mannosyl Tryptophan in Chemical Biology and Medicine

Synthesis of C-Mannosylated Glycopeptides Enabled by Ni-Catalyzed Photoreductive Cross-Coupling Reactions

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Total Synthesis of C-α-Mannosyl Tryptophan via Palladium-Catalyzed C–H Glycosylation

Cited by 57 publications

References 40 publications

Visible‐Light‐Promoted Stereoselective C(sp3)−H Glycosylation for the Synthesis of C‐Glycoamino Acids and C‐Glycopeptides

Visible‐Light‐Promoted Stereoselective C(sp3)−H Glycosylation for the Synthesis of C‐Glycoamino Acids and C‐Glycopeptides

Protein C-Mannosylation and C-Mannosyl Tryptophan in Chemical Biology and Medicine

Synthesis of C-Mannosylated Glycopeptides Enabled by Ni-Catalyzed Photoreductive Cross-Coupling Reactions

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Product

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Visible‐Light‐Promoted Stereoselective C(sp³)−H Glycosylation for the Synthesis of C‐Glycoamino Acids and C‐Glycopeptides

Visible‐Light‐Promoted Stereoselective C(sp³)−H Glycosylation for the Synthesis of C‐Glycoamino Acids and C‐Glycopeptides