- Highly Stereoselective Glycosylation Reactions of Furanoside Derivatives via Rhenium (V) Catalysis
-
A novel approach for the formation of anomeric carbon-functionalized furanoside systems was accomplished through the employment of an oxo-rhenium catalyst. The transformation boasts a broad range of nucleophiles including allylsilanes, enol ethers, and aromatics in addition to sulfur, nitrogen, and hydride donors, able to react with an oxocarbenium ion intermediate derived from furanosidic structures. The excellent stereoselectivities observed followed the Woerpel model, ultimately providing 1,3-cis-1,4-trans systems. In the case of electron-rich aromatic nucleophiles, an equilibration occurs at the anomeric center with the selective formation of 1,3-trans-1,4-cis systems. This anomalous result was rationalized through density functional theory calculations. Different oxocarbenium ions such as those derived from dihydroisobenzofuran, pyrrolidine, and oxazolidine heterocycles can also be used as a substrate for the oxo-Re-mediated allylation reaction.
- Casali, Emanuele,Othman, Sirwan T.,Dezaye, Ahmed A.,Chiodi, Debora,Porta, Alessio,Zanoni, Giuseppe
-
p. 7672 - 7686
(2021/06/21)
-
- Glycosides and Glycoconjugates of the Diterpenoid Isosteviol with a 1,2,3-Triazolyl Moiety: Synthesis and Cytotoxicity Evaluation
-
Several glycoconjugates of the diterpenoid isosteviol (16-oxo-ent-beyeran-19-oic acid) with a 1,2,3-triazolyl moiety were synthesized, and their cytotoxicity was evaluated against some human cancer and normal cell lines. Most of the synthesized compounds demonstrated weak inhibitory activities against the M-HeLa and MCF-7 human cancer cell lines. Three lead compounds, 54, 56 and 57, exhibited high selective cytotoxic activity against M-HeLa cells (IC50 = 1.7-1.9 μM) that corresponded to the activity of the anticancer drug doxorubicin (IC50 = 3.0 μM). Moreover, the lead compounds were not cytotoxic with respect to a Chang liver human normal cell line (IC50 > 100 μM), whereas doxorubicin was cytotoxic to this cell line (IC50 = 3.0 μM). It was found that cytotoxic activity of the lead compounds is due to induction of apoptosis proceeding along the mitochondrial pathway. The present findings suggest that 1,2,3-triazolyl-ring-containing glycoconjugates of isosteviol are a promising scaffold for the design of novel anticancer agents.
- Andreeva, Olga V.,Garifullin, Bulat F.,Sharipova, Radmila R.,Strobykina, Irina Yu.,Sapunova, Anastasiya S.,Voloshina, Alexandra D.,Belenok, Mayya G.,Dobrynin, Alexey B.,Khabibulina, Leysan R.,Kataev, Vladimir E.
-
p. 2367 - 2380
(2020/08/28)
-
- Process and intermediate compounds for the preparation of pyrrolidines
-
Processes for the preparation of pyrrolidones (7 and 8) and pyrrolidines (9 and 10) from tri-O-acetyl-D-erythro-4-pentulosonic acid esters are described. The compounds are aza sugar analogs of D-ribofuranoside and are intermediates to drugs which regulate nucleoside and nucleic acid synthesis.
- -
-
-
- Oxidation of acetylated guanosine by 3,3-disubstituted 1,2-dioxetanes through nucleophilic attack on the peroxide bond: Model studies on the oxidative DNA damage by reactive peroxides
-
The reaction of the disubstituted 3-(methoxymethyl)-3-phenyl-1,2-dioxetane (1a) with the acetylated guanine nucleoside (2) in methanol affords 8-methoxyguanosine 5 as oxidation product, as well as guanine (6) and 1-methoxyribose 7 by deglycosylation (total yield ca. 30%). The dioxetane-derived reduction product constitutes the 1,2-diol 4a, while the major dioxetane-derived product (85%) is ω-methoxyacetophenone (3a). A Grob-type fragmentation is made responsible for the exclusive formation of the dioxetane cleavage products in the reactions with the acetylated nucleosides 8-10 derived from adenine, cytosine, and thymine. Rather than redox chemistry, this guanosine oxidation, unprecedented for peroxides, is proposed to involve nucleophilic attack by the N-7 atom of the nucleosides on the peroxide bond of the dioxetane 1a electrophile to generate a zwitterionic intermediate. S(N)2 attack by methanol at the C-8 position of the guanine moiety in the zwitterionic intermediate leads to the 8-methoxyguanosine 5 and the diol 4a. Alternatively, heterolytic cleavage of the glycosidic bond affords the methoxylated ribose 7 (after methanol trapping) and the N-7-alkoxylated guanine. The latter, after protonation, subsequently undergoes Grob fragmentation into guanine (6) and the dioxetane decomposition products ω-methoxyacetophenone (3a) and formaldehyde. We propose that the present novel oxidation of guanosine is general for electrophilic peroxides and may constitute a prominent route of oxidative DNA damage. In contrast, the corresponding 3-(bromomethyl)-3-phenyl-1,2-dioxetane (1b) gave with the guanosine 2 an intractable, complex product mixture, for which presumably the bromo substituent is responsible on account of competitive alkylation chemistry. However, with the 2'-deoxythymidine 10, a novel acid-catalyzed ring-opening of the bromo-substituted dioxetane 1b to its β-methoxy hydroperoxide 11b is observed, a reaction which does not take place for the methoxy-substituted dioxetane 1a. This unusual process for simple dioxetanes is rationalized in terms of stabilization of the intermediary benzylic cation by the adjacent β-bromo substituent through neighboring group participation.
- Adam, Waldemar,Treiber, Alexander
-
p. 2686 - 2693
(2007/10/02)
-
