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Accessing Challenging O- and C-Glycoside Linkages from Shelf-Stable Functionalities.

Record Type:	Language materials, manuscript : Monograph/item
Title/Author:	Accessing Challenging O- and C-Glycoside Linkages from Shelf-Stable Functionalities./
Author:	Romeo, Joseph R.
Description:	1 online resource (567 pages)
Notes:	Source: Dissertations Abstracts International, Volume: 85-03, Section: B.
Contained By:	Dissertations Abstracts International85-03B.
Subject:	Organic chemistry. -
Online resource:	click for full text (PQDT)
ISBN:	9798380340915

Accessing Challenging O- and C-Glycoside Linkages from Shelf-Stable Functionalities.
Romeo, Joseph R.

Accessing Challenging O- and C-Glycoside Linkages from Shelf-Stable Functionalities. - 1 online resource (567 pages)

Source: Dissertations Abstracts International, Volume: 85-03, Section: B.

Thesis (Ph.D.)--Tufts University, 2023.

Includes bibliographical references

A major challenge in the synthesis and derivatization of sugar natural products and glycobiological probes is the development of user-friendly, efficient glycosylation methods by which to connect monosaccharide units. While glycosylation methods to connect common, mammalian glycosides have evolved considerably in recent years, a significant challenge remains in the construction of deoxygenated O-glycosides and alkyl-C-glycosides. This dissertation describes the development of two direct glycosylation methods to generate 2-deoxy bacterial secondary metabolite fragments and alkyl exo-C-glycosides from shelf-stable precursors.Chapter 1 summarizes the current approaches to direct O- and C-glycosylation and further describes the significance of these methods in the context of glycobiology and therapeutic discovery. Recent developments by the Bennett lab in reagent-controlled dehydrative O- and C-glycosylation are further highlighted as key background for further method development. Chapter 2 highlights the extension of one such α-selective dehydrative glycosylation method to the synthesis of the 2,6-dideoxy L-oliose tetrasaccharide of the anthracycline natural product Arugomycin (AGM). This method utilizes a third-generation promoter system of aryl cyclopropene thione and oxalyl bromide to generate active glycosyl donors in situ from shelf stable hemiacetals. A convergent synthesis to reach the AGM tetrasaccharide by this method is described.Chapter 3 describes the development of a novel, Ni-catalyzed alkyl exo-C-glycosylation of shelf-stable anomeric tetra-chloro-N-hydroxyphthalimide (TCNHPI) redox-active esters. By this approach, alkyl C-glycosides are formed in one pot from TCNHPI esters and alkylzinc reagents by a decarboxylative, Negishi-type process. Importantly, these C-glycosylations could be conducted using standard Schlenk-line techniques and without the use of a specialized light source. The optimization of this method by extensive ligand screening, and subsequent application to the synthesis of various linear alkyl C-Glucosides and C-Galactosides, is also described. Chapter 4, lastly, illustrates the extension of this Ni-catalyzed approach to the synthesis of α-alkoxy furan-containing C-glycosides, which were further elaborated to CH2-linked disaccharides by Achmatowicz rearrangement and subsequent derivatization. A strategy for characterization of the resulting CH2-linked Glc-1,6-Man C-disaccharides by 2D-NMR and NOE experiments, is also described.

Electronic reproduction.
Ann Arbor, Mich. :
ProQuest,
2024

Mode of access: World Wide Web

ISBN: 9798380340915Subjects--Topical Terms:

1148722
Organic chemistry.
Subjects--Index Terms:

BioisostereIndex Terms--Genre/Form:

554714
Electronic books.

Accessing Challenging O- and C-Glycoside Linkages from Shelf-Stable Functionalities.
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504 $a Includes bibliographical references
520 $a A major challenge in the synthesis and derivatization of sugar natural products and glycobiological probes is the development of user-friendly, efficient glycosylation methods by which to connect monosaccharide units. While glycosylation methods to connect common, mammalian glycosides have evolved considerably in recent years, a significant challenge remains in the construction of deoxygenated O-glycosides and alkyl-C-glycosides. This dissertation describes the development of two direct glycosylation methods to generate 2-deoxy bacterial secondary metabolite fragments and alkyl exo-C-glycosides from shelf-stable precursors.Chapter 1 summarizes the current approaches to direct O- and C-glycosylation and further describes the significance of these methods in the context of glycobiology and therapeutic discovery. Recent developments by the Bennett lab in reagent-controlled dehydrative O- and C-glycosylation are further highlighted as key background for further method development. Chapter 2 highlights the extension of one such α-selective dehydrative glycosylation method to the synthesis of the 2,6-dideoxy L-oliose tetrasaccharide of the anthracycline natural product Arugomycin (AGM). This method utilizes a third-generation promoter system of aryl cyclopropene thione and oxalyl bromide to generate active glycosyl donors in situ from shelf stable hemiacetals. A convergent synthesis to reach the AGM tetrasaccharide by this method is described.Chapter 3 describes the development of a novel, Ni-catalyzed alkyl exo-C-glycosylation of shelf-stable anomeric tetra-chloro-N-hydroxyphthalimide (TCNHPI) redox-active esters. By this approach, alkyl C-glycosides are formed in one pot from TCNHPI esters and alkylzinc reagents by a decarboxylative, Negishi-type process. Importantly, these C-glycosylations could be conducted using standard Schlenk-line techniques and without the use of a specialized light source. The optimization of this method by extensive ligand screening, and subsequent application to the synthesis of various linear alkyl C-Glucosides and C-Galactosides, is also described. Chapter 4, lastly, illustrates the extension of this Ni-catalyzed approach to the synthesis of α-alkoxy furan-containing C-glycosides, which were further elaborated to CH2-linked disaccharides by Achmatowicz rearrangement and subsequent derivatization. A strategy for characterization of the resulting CH2-linked Glc-1,6-Man C-disaccharides by 2D-NMR and NOE experiments, is also described.
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