Clay S. Bennett

Bio: Clay S. Bennett is an academic researcher from Tufts University. The author has contributed to research in topics: Glycosylation & Glycosyl. The author has an hindex of 22, co-authored 62 publications receiving 1422 citations. Previous affiliations of Clay S. Bennett include University of Pennsylvania & Monell Chemical Senses Center.

Methods for 2-Deoxyglycoside Synthesis.

Abstract: Deoxy-sugars often play a critical role in modulating the potency of many bioactive natural products. Accordingly, there has been sustained interest in methods for their synthesis over the past several decades. The focus of much of this work has been on developing new glycosylation reactions that permit the mild and selective construction of deoxyglycosides. This Review covers classical approaches to deoxyglycoside synthesis, as well as more recently developed chemistry that aims to control the selectivity of the reaction through rational design of the promoter. Where relevant, the application of this chemistry to natural product synthesis will also be described.

A reagent-controlled SN2-glycosylation for the direct synthesis of β-linked 2-deoxy-sugars.

Abstract: The efficient and stereoselective construction of glycosidic linkages remains one of the most formidable challenges in organic chemistry. This is especially true in cases such as β-linked deoxy-sugars, where the outcome of the reaction cannot be controlled using the stereochemical information intrinsic to the glycosyl donor. Here we show that p-toluenesulfonic anhydride activates 2-deoxy-sugar hemiacetals in situ as electrophilic species, which react stereoselectively with nucleophilic acceptors to produce β-anomers exclusively. NMR studies confirm that, under these conditions, the hemiacetal is quantitatively converted into an α-glycosyl tosylate, which is presumably the reactive species in the reaction. This approach demonstrates that use of promoters that activate hemiacetals as well-defined intermediates can be used to permit stereoselective glycosylation through an SN2-pathway.

Chemoenzymatic elaboration of monosaccharides using engineered cytochrome P450BM3 demethylases

Abstract: Polysaccharides comprise an extremely important class of biopolymers that play critical roles in a wide range of biological processes, but the synthesis of these compounds is challenging because of their complex structures We have developed a chemoenzymatic method for regioselective deprotection of monosaccharide substrates using engineered Bacillus megaterium cytochrome P450 (P450BM3) demethylases that provides a highly efficient means to access valuable intermediates, which can be converted to a wide range of substituted monosaccharides and polysaccharides Demethylases displaying high levels of regioselectivity toward a number of protected monosaccharides were identified using a combination of protein and substrate engineering, suggesting that this approach ultimately could be used in the synthesis of a wide range of substituted mono- and polysaccharides for studies in chemistry, biology, and medicine

Chemoenzymatic approaches to glycoprotein synthesis

Abstract: The construction of homogeneous glycoproteins presents a formidable challenge to the synthetic chemist. Over the past few years there has been an explosion in the number of methods developed to address this problem. These methods include the development of novel ligation technologies for the synthesis of the protein backbone, as well chemical and enzymatic approaches for introducing complex glycans into the peptide backbone. This tutorial review discusses the application of these techniques to the synthesis of peptides and proteins possessing well defined glycans.

Natural product synthesis using multicomponent reaction strategies.

Abstract: The preparation of urea by Wöhler constituted a landmark achievement in organic chemistry, and it laid the ground for the early days of target-oriented organic synthesis.1 Since then, significant progress has been achieved in this discipline; many powerful single bond forming reactions and asymmetric variants have been developed. These discoveries have paved the way for the stereoselective assembly of complex organic molecules, a task deemed inconceivable by early practitioners. A great many strategies were invented by chemists in order to facilitate the synthesis of complex natural products.2 One avenue in emulating nature’s efficiency would * To whom correspondence should be addressed. E-mail: dennis.hall@ ualberta.ca. † Novartis Institute for Biomedical Research. ‡ Department of Chemistry, University of Alberta. Chem. Rev. 2009, 109, 4439–4486 4439

Advances in Synthetic Applications of Hypervalent Iodine Compounds

Abstract: The preparation, structure, and chemistry of hypervalent iodine compounds are reviewed with emphasis on their synthetic application. Compounds of iodine possess reactivity similar to that of transition metals, but have the advantage of environmental sustainability and efficient utilization of natural resources. These compounds are widely used in organic synthesis as selective oxidants and environmentally friendly reagents. Synthetic uses of hypervalent iodine reagents in halogenation reactions, various oxidations, rearrangements, aminations, C–C bond-forming reactions, and transition metal-catalyzed reactions are summarized and discussed. Recent discovery of hypervalent catalytic systems and recyclable reagents, and the development of new enantioselective reactions using chiral hypervalent iodine compounds represent a particularly important achievement in the field of hypervalent iodine chemistry. One of the goals of this Review is to attract the attention of the scientific community as to the benefits of...

Chemoselective Ligation and Modification Strategies for Peptides and Proteins

Abstract: The investigation of biological processes by chemical methods, commonly referred to as chemical biology, often requires chemical access to biologically relevant macromolecules such as peptides and proteins. Building upon solid-phase peptide synthesis, investigations have focused on the development of chemoselective ligation and modification strategies to link synthetic peptides or other functional units to larger synthetic and biologically relevant macromolecules. This Review summarizes recent developments in the field of chemoselective ligation and modification strategies and illustrates their application, with examples ranging from the total synthesis of proteins to the semisynthesis of naturally modified proteins.