- A Chemoenzymatic Route to Prepare Acyclic Nucleoside Analogues
-
Acyclic nucleosides are potential antiviral and antitumor agents. In this work, their preparation through a novel chemoenzymatic procedure involving the N-alkylation of a nucleobase and subsequent aldol condensation catalyzed by a dihydroxyacetone phosphate-dependant aldolase (Rabbit Muscle Aldolase, RAMA) is described.
- Palazzolo, Martín A.,Nigro, Mariano J.,Iribarren, Adolfo M.,Lewkowicz, Elizabeth Sandra
-
-
Read Online
- A short de novo synthesis of nucleoside analogs
-
Nucleoside analogs are commonly used in the treatment of cancer and viral infections. Their syntheses benefit from decades of research but are often protracted, unamenable to diversification, and reliant on a limited pool of chiral carbohydrate starting materials. We present a process for rapidly constructing nucleoside analogs from simple achiral materials. Using only proline catalysis, heteroaryl-substituted acetaldehydes are fluorinated and then directly engaged in enantioselective aldol reactions in a one-pot reaction. A subsequent intramolecular fluoride displacement reaction provides a functionalized nucleoside analog. The versatility of this process is highlighted in multigram syntheses of D- or L-nucleoside analogs, locked nucleic acids, iminonucleosides, and C2′- and C4′-modified nucleoside analogs. This de novo synthesis creates opportunities for the preparation of diversity libraries and will support efforts in both drug discovery and development.
- Adluri, Bharanishashank,Britton, Robert,Campeau, Louis-Charles,Cohen, Ryan,Lehmann, Johannes,Meanwell, Michael,Silverman, Steven M.,Wang, Yang
-
p. 725 - 730
(2020/09/02)
-
- Efficient one-pot, three-component procedure to prepare new α-aminophosphonate and phosphonic acid acyclic nucleosides
-
An efficient one-pot three-component Kabachnik–Fields reaction of aldehydes (acyclic nucleosides), amines (or amino acid), and triethyl phosphite proceeded for the synthesis of aminophosphonates using natural phosphate coated with iodine (I2@NP) as a catalyst. The novel α-aminophosphonate and phosphonic acid acyclic nucleosides were tested for their anti-HCV and anti-HIV activities. The molecular docking showed that the non-activity of these compounds could be due to the absence of hydrophobic pharmacophores.
- Baddi, Laila,Ouzebla, Driss,El Mansouri, Az-Eddine,Smietana, Michael,Vasseur, Jean-Jacques,Lazrek, Hassan B.
-
-
- Synthesis of novel mimetics of CMP-sialic acid as the inhibitors of sialyltransferases
-
Novel mimetics of CMP-sialic acid were designed as the inhibitors of sialyltransferases. They were synthesized in a short step from a cytosine carrying β-hydroxy-α-L-amino acid based on the knowledge that nikkomycin, a peptidic derivative of an uracil carrying amino acid, shows a potent inhibitory activity toward N-acetyl-D-glucosaminyltransferases that employ UDP-N-acetyl-D-glucosamine as the donor substrate. The cytosine carrying β-hydroxyl-α-L-amino acid, a key intermediate in our synthetic strategy, was easily prepared by the L-threonine aldolase (LTA) catalyzed reaction.
- Tanaka, Toru,Ozawa, Machiko,Miura, Tsuyoshi,Inazu, Toshiyuki,Tsuji, Shuichi,Kajimoto, Tetsuya
-
p. 1487 - 1490
(2007/10/03)
-