From cyclopentadiene to isoxazoline-carbocyclic nucleosides: a rapid access to biological molecules through aza-Diels–Alder reactions

Iminium Ions as Dienophiles in Aza‐Diels–Alder Reactions: A Closer Look

“…[36] The aldehydes 55 were easily converted into the aminols 57 (Scheme 17), which were used for the linear construction of purine rings in the synthesis of a variety of nucleoside derivatives. [37] In the search for a fast and convenient oxidation protocol, we took advantage of the oxidative ability of RuO 4 ; [38] the oxidation step was in fact considered the most We also investigated the RuO 4 -catalysed oxidation reactions of N-alkyl-substituted 2-azanorborn-5-ene derivatives as a shortcut to valuable bridged g-lactams, which are potential analogues of classical b-lactam antibiotics. [40] N-Alkylsubstituted 2-azanorborn-5-enes 61 A-D were prepared by the addition of freshly distilled cyclopentadiene to an aqueous solution of the required amine hydrochlorides and formaldehyde (37 %), according to the typical Griecos procedure.…”

“…The aldehydes 55 were easily converted into the aminols 57 (Scheme ), which were used for the linear construction of purine rings in the synthesis of a variety of nucleoside derivatives 37. In the search for a fast and convenient oxidation protocol, we took advantage of the oxidative ability of RuO 4 ;38 the oxidation step was in fact considered the most difficult of the overall pathway towards the aminols.…”

“…The authors concluded that the 2-azabicyclic amino acid derivatives that were obtained from iADA reactions are of considerable interest as valuable starting materials for the straightforward construction of carbonucleosides. [35][36][37]64] In this context, Pombo-Villar and co-workers noticed that the azanorbornene moiety could mimic the 2,4,6-tetrahydropyrine core that is present in the natural product arecoline, which is a muscarinic agonist. [65] A detailed study of the features of muscarinic agonists allowed the identification of the exo-2-methyl-5-carbomethoxy-2-azabicycloA C H T U N G T R E N N U N G [2.2.1]heptane isomers 116, which best fit the geometrical constraints required for selective interactions with the muscarinic receptors.…”

Molecular modeling studies of pseudouridine isoxazolidinyl nucleoside analogues as potential inhibitors of the pseudouridine 5ʹ‐monophosphate glycosidase

“…[8,11] The genes encoding these proteins are absent from the genomes of man and other mammals; normally, this nucleoside is present in human urine, and its concentration is increased in tumor-bearing patients. [21][22][23][24][25][26][27][28][29] In our research group, isoxazolidine replacement has also been employed for Ψ modification, leading to the development of the isoxazolidinyl-C-nucleosides 1-3 ( Figure 1). [13,14] The majority of nucleoside analogs consist of modifications of the natural substrates in the heterocyclic base and/or the sugar moiety.…”

“…[15] Isoxazolidine ring has been extensively used as a simplified alternative to the nucleoside sugar. [21][22][23][24][25][26][27][28][29] In our research group, isoxazolidine replacement has also been employed for Ψ modification, leading to the development of the isoxazolidinyl-C-nucleosides 1-3 ( Figure 1). [30] In light of the mechanism of the Ψ cleavage, [11] the peculiar reactivity of the isoxazolidine ring could prevent the ring-opening process, thus inhibiting the enzyme activity.…”