Total synthesis of aStreptococcus pneumoniaeserotype 12F CPS repeating unit hexasaccharide

The Gram-positive bacteriumStreptococcus pneumoniaecauses severe disease globally. Vaccines that preventS. pneumoniaeinfections induce antibodies against epitopes within the bacterial capsular polysaccharide (CPS). A better immunological understanding of the epitopes that protect from bacterial infection requires defined oligosaccharides obtained by total synthesis. The key to the synthesis of theS. pneumoniaeserotype 12F CPS hexasaccharide repeating unit that is not contained in currently used glycoconjugate vaccines is the assembly of the trisaccharide β-D-GalpNAc-(1→4)-[α-D-Glcp-(1→3)]-β-D-ManpNAcA, in which the branching points are equipped with orthogonal protecting groups. A linear approach relying on the sequential assembly of monosaccharide building blocks proved superior to a convergent [3 + 3] strategy that was not successful due to steric constraints. The synthetic hexasaccharide is the starting point for further immunological investigations.

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Total Synthesis of the Trisaccharide Antigen of theCampylobacter jejuniRM1221 Capsular Polysaccharide via de Novo Synthesis of the 6-Deoxy-d-manno-heptose Building Blocks

The Journal of Organic Chemistry ◽

10.1021/acs.joc.8b02394 ◽

2019 ◽

Vol 84 (5) ◽

pp. 2393-2403 ◽

Cited By ~ 4

Author(s):

Xiaoman Wang ◽

Yan Chen ◽

Junchang Wang ◽

You Yang

Keyword(s):

Total Synthesis ◽

Capsular Polysaccharide ◽

De Novo ◽

Building Blocks ◽

De Novo Synthesis

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Automated glycan assembly of aS. pneumoniaeserotype 3 CPS antigen

Beilstein Journal of Organic Chemistry ◽

10.3762/bjoc.12.139 ◽

2016 ◽

Vol 12 ◽

pp. 1440-1446 ◽

Cited By ~ 11

Author(s):

Markus W Weishaupt ◽

Stefan Matthies ◽

Mattan Hurevich ◽

Claney L Pereira ◽

Heung Sik Hahm ◽

...

Keyword(s):

Process Improvement ◽

Late Stage ◽

Building Block ◽

Bacterial Infections ◽

Capsular Polysaccharide ◽

Glucuronic Acid ◽

Severe Disease ◽

Building Blocks ◽

Oxidation Step ◽

Chain Lengths

Vaccines againstS. pneumoniae, one of the most prevalent bacterial infections causing severe disease, rely on isolated capsular polysaccharide (CPS) that are conjugated to proteins. Such isolates contain a heterogeneous oligosaccharide mixture of different chain lengths and frame shifts. Access to defined syntheticS. pneumoniaeCPS structures is desirable. Known syntheses ofS. pneumoniaeserotype 3 CPS rely on a time-consuming and low-yielding late-stage oxidation step, or use disaccharide building blocks which limits variability. Herein, we report the first iterative automated glycan assembly (AGA) of a conjugation-readyS. pneumoniaeserotype 3 CPS trisaccharide. This oligosaccharide was assembled using a novel glucuronic acid building block to circumvent the need for a late-stage oxidation. The introduction of a washing step with the activator prior to each glycosylation cycle greatly increased the yields by neutralizing any residual base from deprotection steps in the synthetic cycle. This process improvement is applicable to AGA of many other oligosaccharides.

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Total Synthesis and Antimicrobial Evaluation of Pagoamide A

Frontiers in Chemistry ◽

10.3389/fchem.2021.741290 ◽

2021 ◽

Vol 9 ◽

Author(s):

Cheng-Han Wu ◽

John Chu

Keyword(s):

Total Synthesis ◽

Solid Phase ◽

Solid Phase Peptide Synthesis ◽

Building Blocks ◽

Synthetic Methods ◽

Marine Natural Product ◽

Moderate Activity ◽

Starting Point ◽

Antimicrobial Evaluation ◽

Synthetic Sequence

Natural products are often the starting point for drug development and also the testing ground for synthetic methods. Herein we describe the total synthesis and antimicrobial evaluation of a marine natural product, pagoamide A, which is a macrocyclic depsipeptide with two backbone thiazole units and a dimethylated N-terminus. The two thiazole building blocks were synthesized from commercially available materials in four or fewer steps and employed directly in solid-phase peptide synthesis (SPPS) to afford pagoamide A. The use of SPPS ensured that the synthetic sequence is operationally straightforward and, if needed, permits modular substitution of building blocks to easily access diverse structural analogs. Our antimicrobial assays showed that pagoamide A has moderate activity against Bacillus subtilis.

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Non-Enzymatic Desymmetrization Reactions in Aqueous Media

Symmetry ◽

10.3390/sym13040720 ◽

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.

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Xylochemical Synthesis and Biological Evaluation of Shancigusin C and Bletistrin G

Molecules ◽

10.3390/molecules26113224 ◽

2021 ◽

Vol 26 (11) ◽

pp. 3224

Author(s):

Leander Geske ◽

Ulrich Kauhl ◽

Mohamed E. M. Saeed ◽

Anja Schüffler ◽

Eckhard Thines ◽

...

Keyword(s):

Total Synthesis ◽

Biological Activities ◽

Biological Evaluation ◽

Aromatic Substitution ◽

Substitution Reactions ◽

Total Syntheses ◽

Wittig Olefination ◽

Starting Point ◽

Perkin Reaction ◽

Synthesis And Biological Evaluation

The biological activities of shancigusin C (1) and bletistrin G (2), natural products isolated from orchids, are reported along with their first total syntheses. The total synthesis of shancigusin C (1) was conducted by employing the Perkin reaction to forge the central stilbene core, whereas the synthesis of bletistrin G (2) was achieved by the Wittig olefination followed by several regioselective aromatic substitution reactions. Both syntheses were completed by applying only renewable starting materials according to the principles of xylochemistry. The cytotoxic properties of shancigusin C (1) and bletistrin G (2) against tumor cells suggest suitability as a starting point for further structural variation.

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