Corrections to Short and General Procedure for Synthesizing Cis-1,2-Fused 1,3-Oxathiolan-, 1,3-Oxaselenolan-, and 1,3-Oxazolidin-2-Imine Carbohydrate Derivatives

Corrections to Short and General Procedure for Synthesizing Cis-1,2-Fused 1,3-Oxathiolan-, 1,3-Oxaselenolan-, and 1,3-Oxazolidin-2-Imine Carbohydrate Derivative

Tuning the Stereoelectronic Properties of 1‑Sulfanylhex-1-enitols for the Sequential Stereoselective Synthesis of 2‑Deoxy-2-iodo-β‑d‑allopyranosides

The preparation of challenging 2-deoxy-2-iodo-β-d-<i>allo</i> precursors of 2-deoxy-β-d-<i>ribo</i>-hexopyranosyl units and other analogues is reported using a robust olefination–cyclization–glycosylation sequence. Here, we particularly focus on tuning the stereoelectronic properties of the alkenyl sulfides intermediates in order to improve the diastereoselectivity of the cyclization step and, hence, the efficiency of the overall transformation. Phosphine oxides with the general formula Ph₂P­(O)­CH₂SR (R = <i>t</i>-Bu, Cy, <i>p</i>-MeOPh, 2,6-di-ClPh, and 2,6-di-MePh) were easily synthesized and subsequently used in the olefination reaction with 2,3,5-tri-<i>O</i>-benzyl-d-ribose and -d-arabinose. The corresponding sugar-derived alkenyl sulfides were submitted to a <i>6-endo</i> [I⁺]-induced cyclization, and the resulting 2-deoxy-2-iodohexopyranosyl-1-thioglycosides were used as glycosyl donors for the stereoselective synthesis of 2-deoxy-2-iodohexopyranosyl glycosides. Among the different <i>S</i>-groups studied, <i>t</i>-Bu derivative was the best performer for the synthesis of cholesteryl 2-deoxy-2-iodomannopyranosides, whereas for the synthesis of 2-deoxy-2-iodoallopyranosides none of the derivatives here studied proved superior to the phenyl analogue previously described. Glycosylation of cholesterol with different d-<i>allo</i> and d-<i>manno</i> derivatives produced 2-deoxy-2-iodoglycosides with stereoselectivities in the same order in each case, reinforcing the involvement of an oxocarbenium ion as the common intermediate of this crucial glycosylation step

Chemical Access to d‑Sarmentose Units Enables the Total Synthesis of Cardenolide Monoglycoside N‑1 from <i>Nerium oleander</i>

Herein we present a chemical approach for the ready preparation of d-sarmentosyl donors enabling the first total synthesis and structure validation of cardenolide N-1, a challenging 2,6-dideoxy-3-<i>O</i>-methyl-β-d-<i>xylo</i>-hexopyranoside extracted from <i>Nerium oleander</i> twigs that displays anti-inflammatory properties and cell growth inhibitory activity against tumor cells. The strategy highlights the synthetic value of the sequential methodology developed in our group for the synthesis of 2-deoxyglycosides. Key steps include Wittig–Horner olefination of a d-xylofuranose precursor, [I⁺]-induced 6-<i>endo</i> cyclization, and 1,2-<i>trans</i> stereoselective glycosylation

Chemical Access to d‑Sarmentose Units Enables the Total Synthesis of Cardenolide Monoglycoside N‑1 from <i>Nerium oleander</i>

Herein we present a chemical approach for the ready preparation of d-sarmentosyl donors enabling the first total synthesis and structure validation of cardenolide N-1, a challenging 2,6-dideoxy-3-<i>O</i>-methyl-β-d-<i>xylo</i>-hexopyranoside extracted from <i>Nerium oleander</i> twigs that displays anti-inflammatory properties and cell growth inhibitory activity against tumor cells. The strategy highlights the synthetic value of the sequential methodology developed in our group for the synthesis of 2-deoxyglycosides. Key steps include Wittig–Horner olefination of a d-xylofuranose precursor, [I⁺]-induced 6-<i>endo</i> cyclization, and 1,2-<i>trans</i> stereoselective glycosylation

Syntheses of a Novel Fluorinated Trisphosphinoborate Ligand and Its Copper and Silver Complexes. Catalytic Activity toward Nitrene Transfer Reactions

A novel fluorinated ligand, the anionic PhB­(CH₂P­(<i>p</i>-CF₃C₆H₄)₂)₃ (PhBP₃ ^{<i>p</i>‑CF3Ph}), has been synthesized and characterized, as well as its corresponding thallium, copper, and silver derivatives. The presence of fluorine atoms in the ligand structure induced the desired effect of enhancing electrophilic character at the metal center, without promoting substantial changes in the ligand skeleton compared with the parent ligand PhB­(CH₂PPh₂)₃⁻ (PhBP₃). Olefin aziridination and C–H amidation reactions have been induced with those complexes as catalyst precursors. The copper derivative catalyzed the olefin aziridination of an array of olefins bearing either electron-donating or electron-withdrawing groups. The silver analogue was found to promote the C–H amidation of a series of substrates in moderate to high yields

Syntheses of a Novel Fluorinated Trisphosphinoborate Ligand and Its Copper and Silver Complexes. Catalytic Activity toward Nitrene Transfer Reactions

A novel fluorinated ligand, the anionic PhB­(CH₂P­(<i>p</i>-CF₃C₆H₄)₂)₃ (PhBP₃ ^{<i>p</i>‑CF3Ph}), has been synthesized and characterized, as well as its corresponding thallium, copper, and silver derivatives. The presence of fluorine atoms in the ligand structure induced the desired effect of enhancing electrophilic character at the metal center, without promoting substantial changes in the ligand skeleton compared with the parent ligand PhB­(CH₂PPh₂)₃⁻ (PhBP₃). Olefin aziridination and C–H amidation reactions have been induced with those complexes as catalyst precursors. The copper derivative catalyzed the olefin aziridination of an array of olefins bearing either electron-donating or electron-withdrawing groups. The silver analogue was found to promote the C–H amidation of a series of substrates in moderate to high yields

Conformationally-Locked <i>N</i>-Glycosides with Selective β-Glucosidase Inhibitory Activity: Identification of a New Non-Iminosugar-Type Pharmacological Chaperone for Gaucher Disease

A series of conformationally locked <i>N</i>-glycosides having a cis-1,2-fused pyranose–1,3-oxazoline-2-thione structure and bearing different substituents at the exocyclic sulfur has been prepared. The polyhydroxylated bicyclic system was built in only three steps by treatment of the corresponding readily available 1,2-anhydrosugar with KSCN using TiO­(TFA)₂ as catalyst, followed by S-alkylation and acetyl deprotection. In vitro screening against several glycosidase enzymes showed highly specific inhibition of mammalian β-glucosidase with a marked dependence of the potency upon the nature of the exocyclic substituent. The most potent representative, bearing an <i>S</i>-(ω-hydroxyhexadecyl) substituent, was further assayed as inhibitor of the human lysosomal β-glucocerebrosidase and as pharmacological chaperone in Gaucher disease fibroblasts. Activity enhancements in N370S/N370S mutants analogous to those achieved with the reference compound ambroxol were attained with a more favorable chaperone/inhibitor balance