scholarly journals Chemical Synthesis of Rare, Deoxy-Amino Sugars Containing Bacterial Glycoconjugates as Potential Vaccine Candidates

Molecules ◽  
2018 ◽  
Vol 23 (8) ◽  
pp. 1997 ◽  
Author(s):  
Archanamayee Behera ◽  
Suvarn Kulkarni
Keyword(s):  
Chemical Synthesis ◽  
Total Synthesis ◽  
Structural Difference ◽  
Building Blocks ◽  
Host Cells ◽  
Amino Sugars ◽  
Rare Sugar ◽  
Vaccine Candidates ◽  
Potential Vaccine ◽  
Remarkable Progress

Bacteria often contain rare deoxy amino sugars which are absent in the host cells. This structural difference can be harnessed for the development of vaccines. Over the last fifteen years, remarkable progress has been made toward the development of novel and efficient protocols for obtaining the rare sugar building blocks and their stereoselective assembly to construct conjugation ready bacterial glycans. In this review, we discuss the total synthesis of a variety of rare sugar containing bacterial glycoconjugates which are potential vaccine candidates.

Computationally Augmented Retrosynthesis: Total Synthesis of Paspaline A and Emindole PB

2018 ◽  
Author(s):  
Timothy Newhouse ◽  
Daria E. Kim ◽  
Joshua E. Zweig
Keyword(s):  
Chemical Synthesis ◽  
Total Synthesis ◽  
Small Molecules ◽  
First Principles ◽  
Quantum Chemical ◽  
Computational Analysis ◽  
Empirical Evaluation ◽  
Synthetic Strategy ◽  
Catalyzed Reactions ◽  
Enzyme Catalyzed Reactions

The diverse molecular architectures of terpene natural products are assembled by exquisite enzyme-catalyzed reactions. Successful recapitulation of these transformations using chemical synthesis is hard to predict from first principles and therefore challenging to execute. A means of evaluating the feasibility of such chemical reactions would greatly enable the development of concise syntheses of complex small molecules. Herein, we report the computational analysis of the energetic favorability of a key bio-inspired transformation, which we use to inform our synthetic strategy. This approach was applied to synthesize two constituents of the historically challenging indole diterpenoid class, resulting in a concise route to (–)-paspaline A in 9 steps from commercially available materials and the first pathway to and structural confirmation of emindole PB in 13 steps. This work highlights how traditional retrosynthetic design can be augmented with quantum chemical calculations to reveal energetically feasible synthetic disconnections, minimizing time-consuming and expensive empirical evaluation.

Development of Strategies for Glycopeptide Synthesis: An Overview on the Glycosidic Linkage

2020 ◽  
Vol 24 (21) ◽  
pp. 2475-2497
Author(s):  
Andrea Verónica Rodríguez-Mayor ◽  
German Jesid Peralta-Camacho ◽  
Karen Johanna Cárdenas-Martínez ◽  
Javier Eduardo García-Castañeda
Keyword(s):  
Chemical Synthesis ◽  
Solid Phase ◽  
Building Blocks ◽  
Heterogeneous Environments ◽  
Phase Synthesis ◽  
Low Concentrations ◽  
Biological Sources ◽  
Synthetic Routes ◽  
The Impact ◽  
Potential Use

Glycoproteins and glycopeptides are an interesting focus of research, because of their potential use as therapeutic agents, since they are related to carbohydrate-carbohydrate, carbohydrate-protein, and carbohydrate-lipid interactions, which are commonly involved in biological processes. It has been established that natural glycoconjugates could be an important source of templates for the design and development of molecules with therapeutic applications. However, isolating large quantities of glycoconjugates from biological sources with the required purity is extremely complex, because these molecules are found in heterogeneous environments and in very low concentrations. As an alternative to solving this problem, the chemical synthesis of glycoconjugates has been developed. In this context, several methods for the synthesis of glycopeptides in solution and/or solid-phase have been reported. In most of these methods, glycosylated amino acid derivatives are used as building blocks for both solution and solid-phase synthesis. The synthetic viability of glycoconjugates is a critical parameter for allowing their use as drugs to mitigate the impact of microbial resistance and/or cancer. However, the chemical synthesis of glycoconjugates is a challenge, because these molecules possess multiple reaction sites and have a very specific stereochemistry. Therefore, it is necessary to design and implement synthetic routes, which may involve various protection schemes but can be stereoselective, environmentally friendly, and high-yielding. This review focuses on glycopeptide synthesis by recapitulating the progress made over the last 15 years.

scholarly journals Non-Enzymatic Desymmetrization Reactions in Aqueous Media

Symmetry ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 720
Author(s):  
Satomi Niwayama
Keyword(s):  
Natural Products ◽  
Total Synthesis ◽  
Functional Groups ◽  
Organic Compounds ◽  
Recent Progress ◽  
Aqueous Media ◽  
Building Blocks ◽  
Organic Reactions ◽  
Environmentally Benign ◽  
Enzymatic Desymmetrization

Symmetric organic compounds are generally obtained inexpensively, and therefore they can be attractive building blocks for the total synthesis of various pharmaceuticals and natural products. The drawback is that discriminating the identical functional groups in the symmetric compounds is difficult. Water is the most environmentally benign and inexpensive solvent. However, successful organic reactions in water are rather limited due to the hydrophobicity of organic compounds in general. Therefore, desymmetrization reactions in aqueous media are expected to offer versatile strategies for the synthesis of a variety of significant organic compounds. This review focuses on the recent progress of desymmetrization reactions of symmetric organic compounds in aqueous media without utilizing enzymes.

Probing the SAR of dEpoB via Chemical Synthesis:  A Total Synthesis Evaluation of C26-(1,3-dioxolanyl)-12,13-desoxyepothilone B

2002 ◽  
Vol 67 (22) ◽  
pp. 7730-7736 ◽  
Author(s):  
Mark D. Chappell ◽  
Christina R. Harris ◽  
Scott D. Kuduk ◽  
Aaron Balog ◽  
Zhicai Wu ◽  
...  
Keyword(s):  
Chemical Synthesis ◽  
Total Synthesis

Total Synthesis of Woodrosin I. Part 1. Preparation of the Building Blocks and Evaluation of the Glycosylation Strategy.

ChemInform ◽  
2003 ◽  
Vol 34 (18) ◽  
Author(s):  
Alois Fuerstner ◽  
Fabien Jeanjean ◽  
Patrick Razon ◽  
Conny Wirtz ◽  
Richard Mynott
Keyword(s):  
Total Synthesis ◽  
Building Blocks

scholarly journals Assessment of Live Candidate Vaccines for Paratuberculosis in Animal Models and Macrophages

2009 ◽  
Vol 78 (3) ◽  
pp. 1383-1389 ◽  
Author(s):  
Gabriella M. Scandurra ◽  
Geoffrey W. de Lisle ◽  
Sonia M. Cavaignac ◽  
May Young ◽  
R. Pamela Kawakami ◽  
...  
Keyword(s):  
Side Effects ◽  
Bacterial Load ◽  
Economic Effect ◽  
Cost Effective ◽  
The Other ◽  
Murine Models ◽  
Initial Screening ◽  
Vaccine Candidates ◽  
Allelic Exchange ◽  
Potential Vaccine

ABSTRACT Mycobacterium avium subsp. paratuberculosis (basonym M. paratuberculosis) is the causative agent of paratuberculosis, a chronic enteritis of ruminants. To control the considerable economic effect that paratuberculosis has on the livestock industry, a vaccine that induces protection with minimal side effects is required. We employed transposon mutagenesis and allelic exchange to develop three potential vaccine candidates, which were then tested for virulence with macrophages, mice, and goats. All three models identified the WAg906 mutant as being the most attenuated, but some differences in the levels of attenuation were evident among the models when testing the other strains. In a preliminary mouse vaccine experiment, limited protection was induced by WAg915, as evidenced by a reduced bacterial load in spleens and livers 12 weeks following intraperitoneal challenge with M. paratuberculosis K10. While we found macrophages and murine models to be rapid and cost-effective alternatives for the initial screening of M. paratuberculosis mutants for attenuation, it appears necessary to do the definitive assessment of attenuation with a ruminant model.

scholarly journals Chemical synthesis and cytotoxicity of neo-glycolipids; rare sugar-glycerol-lipid compounds

Heliyon ◽  
2018 ◽  
Vol 4 (10) ◽  
pp. e00861 ◽  
Author(s):  
Keisuke Hirata ◽  
Takashi Uchida ◽  
Yoshikata Nakajima ◽  
Toru Maekawa ◽  
Toru Mizuki
Keyword(s):  
Chemical Synthesis ◽  
Rare Sugar ◽  
Lipid Compounds
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