An efficient and large-scale enantioselective synthesis of PNP405: a purine nucleoside phosphorylase inhibitor.

  title={An efficient and large-scale enantioselective synthesis of PNP405: a purine nucleoside phosphorylase inhibitor.},
  author={Mahavir Prashad and Denis Har and Lijian Chen and Hongyong Kim and Oljan Repi{\vc} and Thomas J. Blacklock},
  journal={The Journal of organic chemistry},
  volume={67 19},
An efficient and large-scale enantioselective synthesis of PNP405 (1), a purine nucleoside phosphorylase inhibitor, is described. This synthesis of 1 involved eight steps starting from o-fluorophenylacetic acid with a 21.6% overall yield and >99.5% enantiopurity. The key stereogenic center with (R)-configuration was created using Evans' asymmetric alkylation methodology. This synthesis also features the racemization-free reductive removal of the chiral auxiliary in 5 using sodium borohydride… Expand
Nucleosides as reagents in multicomponent reactions: one-pot synthesis of heterocyclic nucleoside analogues incorporating pyrimidine-fused rings
In this study, a general and efficient protocol for the synthesis of new heterocyclic nucleoside analogues (HNAs), using a four-component coupling reaction of nucleosides, aldehydes, barbituricExpand
An efficient synthesis of 4,6-substituted pyrrolo[3,2-d]pyrimidines by silver-catalyzed cyclization of acetylene amine
Abstract A silver catalyzed cyclization of acetylene amine was developed to synthesize 4,6-substituted pyrrolo[3,2- d ]pyrimidine, a bioactive isosteric scaffold of purine. Starting from simpleExpand
Applications of oxazolidinones as chiral auxiliaries in the asymmetric alkylation reaction applied to total synthesis
Various chiral oxazolidinones (Evans’ oxazolidinones) have been employed as effective chiral auxiliaries in the asymmetric alkylation of different enolates. This strategy has been found promising andExpand
Organocatalytic activation of alkylacetic esters as enolate precursors to react with α,β-unsaturated imines.
A direct catalytic activation of simple alkylacetic esters via N-heterocyclic carbene organocatalysts to generate chiral enolate intermediates for highly enantioselective reactions is reported. Expand
Chromatographic selectivity study of 4-fluorophenylacetic acid positional isomers separation.
A chromatographic analysis of 2- and 3-fluorophenylacetic acid positional isomer impurities in 4-FPAA, a building block in the synthesis of an active pharmaceutical ingredient to eliminate the presence of undesirable positional isomers in the final drug substance is reported. Expand
Large-Scale Carbonyl Reductions in the Pharmaceutical Industry
Herein we present a review on methods for carbonyl reductions on large scale (≥100 mmol) applied to the synthesis of drug candidates in the pharmaceutical industry. We discuss the most common andExpand
3.18 – Nitriles: General Methods and Aliphatic Nitriles
The main interest in the synthesis of aliphatic nitriles since 1995 has been in asymmetric cyanohydrin synthesis and increasingly in asymmetric amino nitrile synthesis. These areas are givenExpand
Conformational equilibrium of phenylacetic acid and its halogenated analogues through theoretical studies, NMR and IR spectroscopy.
It was possible to prove that variation in the nature of the substituent in the ortho position had no significant influence on the conformational equilibrium, and NMR analyses showed that even with the variation in medium polarity, there was no significant change in the conformation population. Expand
Bicyclic 5-6 Systems: Three Heteroatoms 1:2
The literature of 5/6 fused ring systems with one heteroatom in the five-membered ring and two heteroatoms in the six-membered ring is reviewed. The period covered is from the beginning of 1994Expand
Large-Scale Applications of Amide Coupling Reagents for the Synthesis of Pharmaceuticals
This review showcases various coupling reagents which have been implemented specifically for large-scale amide synthesis via the condensation of an acid and amine, while highlighting the benefits andExpand