Synthesis of 3′‐Spiro‐Substituted Nucleosides: Chemistry of TSAO Nucleoside Derivatives

Camarasa, Marı́a-José; Velázquez, Sonsoles; San‐Félix, Ana; Pérez‐Pérez, María‐Jesús

doi:10.1002/9781118498088.ch10

Cited by 3 publications

(5 citation statements)

References 92 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Ethenesulfonyl chloride (10) was prepared in-situ from the treatment of chloro ethyl sulfonyl chloride (9) with TEA under low temperature. The unsaturated sulfonate derivatives (11) were readily prepared by esterification of the secondary alcohols (8) with the in-situ generated ethenesulfonyl chloride (10) in the presence of TEA under low temperature (-40 o C). The structures of the formed sulfonates were confirmed by elemental analysis and spectral data.…”

Section: Methodsmentioning

confidence: 99%

“…Sultones are important scaffolds in organic and bioorganic chemistry with good contribution in the synthesis of different types of heterocycles. [1][2][3][4][5][6] Additionally, Sultones act as sulfoalkylating agents in organic and natural product synthesis 7,8 . Additionally, several publications have reported several biological activities of the sultones that includes antitumor and antiviral (anti-HIV) activities.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Ring closing metathesis and metal-catalyzed cyclopropanation for the preparation of sultone derivatives

Ali¹,

Metz²

2018

Arkivoc

View full text Add to dashboard Cite

Ring closing metathesis (RCM) using Grubbs catalyst 2 nd generation as a catalyst was applied to prepare series of novel unsaturated sultones with high yields. Many attempts, were applied for the cyclopropanation of the allylic sultones by Simmon-smith cyclopropanation using diethyl zinc/diiodomethane or Zn-Cu/diiodomethane but in each case the corresponding cyclic adduct was not formed. A novel palladium or preferably rhodiumcatalyzed cyclopropanation of unsaturated sultones with ethyl diazoacetate was achieved by the transition metal-catalyzed transfer of a CH-CO2Et unit. The reaction was applied by a portion-wise addition of ethyl diazoacetate over 6h to a mixture of the sultones and palladium(II) acetate or rhodium(II) acetate dimer under low temperature (0-20 o C). The desired products of the cyclopropanation were achieved in each case, as a single diastereomer with 33-37% yield in the allylic sultones and 10% for vinylic sultone.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Ring closing metathesis and metal-catalyzed cyclopropanation for the preparation of sultone derivatives

Ali¹,

Metz²

2018

Arkivoc

View full text Add to dashboard Cite

show abstract

“…First interest was given on amine-containing drugs that contain a free amino group that could be directly attached to the carboxyl group of appropriate di-(or oligo)peptide promoieties through an amide bond which may then be specifically hydrolyzed by the DPP IV/CD26 enzyme. [ [63][64][65]. Given that the reactivity of the 4"-amino group of the spirosultone ring moiety is very low [66] (among the more than 900 TSAO derivatives synthesized over the years [65]), the N-3 aminopropyl TSAO-T derivative (NAP-TSAO-T, 2) ( hydrolyzed prodrug 3 to release the parent drug.…”

Section: Dipeptidyl-peptidase Iv/cd26 Enzymementioning

confidence: 99%

“…[ [63][64][65]. Given that the reactivity of the 4"-amino group of the spirosultone ring moiety is very low [66] (among the more than 900 TSAO derivatives synthesized over the years [65]), the N-3 aminopropyl TSAO-T derivative (NAP-TSAO-T, 2) ( hydrolyzed prodrug 3 to release the parent drug. Interestingly, when these stability studies were carried out in the presence of two inhibitors of DPP IV/CD26 (Diprotin A and IlePyr) [69][70][71] the conversion of prodrug to the parent compound was completely blocked.…”

Section: Dipeptidyl-peptidase Iv/cd26 Enzymementioning

confidence: 99%

Dipeptidyl-Peptidase IV (DPP IV/CD26)-Activated Prodrugs: A Successful Strategy for Improving Water Solubility and Oral Bioavailability

Velázquez

Castro²,

Díez-Torrubia³

et al. 2015

CMC

View full text Add to dashboard Cite

In the search of novel enzyme-based prodrug approaches to improve pharmacological properties of therapeutic drugs such as solubility and bioavailability, dipeptidyl-peptidase IV (DPP IV, also termed as CD26) enzyme activity provides a previously unexplored successful prodrug strategy. This review covers key aspects of the enzyme useful for the design of CD26-directed prodrugs. The proof-of-concept of this prodrug technology is provided for amine-containing agents by directly linking appropriate di- (or oligo)peptide moieties to a free amino group of a non-peptidic drug through an amide bond which is specifically hydrolized by DPP IV/CD26. Special emphasis is also made in discussing the design and synthesis of more elaborated tripartite prodrug systems, for further extension of the strategy to hydroxy-containing drugs. The application of this technology to improve water solubility and oral bioavailability of prominent examples of antiviral nucleosides is highlighted.

show abstract

“…Methods used to synthesize sultones and include intramolecular Diels-Alder reactions, ring-closing metathesis, Pd-catalyzed intramolecular coupling reactions, Rh-catalyzed C-H insertion, Rh-catalyzed carbene cyclization cycloaddition cascade reactions, nucleophilic addition reactions etc. [7,8]. The major step in synthesis of sultone is ring-closing reaction which was often complicated by the need to use special and expensive catalysts such as Rh and Pd [8][9][10].…”

Section: Introductionmentioning

confidence: 99%

New Synthesis Method for Sultone Derivatives: Synthesis, Crystal Structure and Biological Evaluation of S-CA

Yan

Zhang

et al. 2015

Molecules

View full text Add to dashboard Cite

There has been no remarkable progress in the synthesis of sultones in recent years. To facilitate more detailed studies of this functional group, we found a new method to synthesize the sulfonic acid lactone derivatives and finish its ring-closing reaction. A new sultone derivative, (E)-ethyl 4-oxo-6-styryl-3,4-dihydro-1,2-oxathiine-5-carboxylate 2,2-dioxide (S-CA), was synthesized and structurally identified by 1 H-NMR, 13 C-NMR, HMQC and X-ray single crystal diffraction analysis. The new rapid synthesis extended the method of ring-closing reaction of sulfonic acid lactone derivatives. The angiogenesis activities of S-CA were evaluated by the chick chorioallantoic membrane (CAM) model. It could selectively suppress small angiogenesis in CAM, without influencing either middle and large angiogenesis. In addition, anticancer efficacy of S-CA was evaluated in vivo using a murine sarcoma S180 model. Reduction of the tumor weight and tumor HE staining regions demonstrated that S-CA (10 mg/kg, intraperitoneal injection) had potent inhibition effects and a 44.71% inhibitory rate in S180 mice. Moreover, an acute toxicity test showed that the LD50 value of S-CA via intraperitoneal injection was 25.624 mg/kg.

show abstract

Synthesis of 3′‐Spiro‐Substituted Nucleosides: Chemistry of TSAO Nucleoside Derivatives

Cited by 3 publications

References 92 publications

Ring closing metathesis and metal-catalyzed cyclopropanation for the preparation of sultone derivatives

Ring closing metathesis and metal-catalyzed cyclopropanation for the preparation of sultone derivatives

Dipeptidyl-Peptidase IV (DPP IV/CD26)-Activated Prodrugs: A Successful Strategy for Improving Water Solubility and Oral Bioavailability

New Synthesis Method for Sultone Derivatives: Synthesis, Crystal Structure and Biological Evaluation of S-CA

Contact Info

Product

Resources

About