Chiral Pyrrolidines

Aldrich ChemFiles 2005, 5.4, 14.

Aldrich ChemFiles 2005, 5.4, 14.

Chiral pyrrolidines are playing an important role both as chiral building blocks for auxiliaries as well as key structures relevant to biologically active substances. Sigma-Aldrich has a large selection of pyrrolidines and other heterocyclic building blocks for organic synthesis and medicinal chemistry, the majority of which are available in both enantiomeric forms. Listed below are selected new chiral pyrrolidines.

2-(Diphenylmethyl)pyrrolidine

Recently, Aggarwal et al. used protonated (S)-(–)-2-(diphenylmethyl)-pyrrolidine as catalyst in a novel process for enantioselective epoxidation of alkenes without the use of a transition metal catalyst (Scheme 29). However, best results were obtained with the chiral pyrrolidine derivative bearing 1-naphthyl groups.1


Scheme 29

Furthermore, both enantiomers of 2-(diphenylmethyl)pyrrolidine have found use as excellent chiral solvating agents to determine the enantiomeric composition of chiral carboxylic acids directly by NMR analysis. Optimal chemical shift non-equivalence between the diastereoisomeric salts is established when a 1:1 salt complex is formed in solution.2

N-tert-Butoxycarbonyl-3-pyrrolidinol

In search of novel compounds for the treatment of acute and chronic pain, pyridyl ethers, were developed by Lee et al. as ligands for the nicotinic acetylcholine receptor as shown in Scheme 30.3 The most potent molecule turned out to be the one bearing the piperidyl ring moiety, which was synthesized from N-Boc-(R)-(+)-3-pyrrolidinol.


Scheme 30

1-Benzyl-3,4-pyrrolidinediol

Enantiomerically pure 3,4-pyrrolidinediols have been extensively studied because of their well-known pharmacological properties as well as serving as powerful chiral building blocks in asymmetric synthesis. (3R,4R)-(–)-1-Benzyl-3,4-pyrrolidinediol served as starting material for the total synthesis of the antibiotic (–)-anisomycin, which exhibits strong and selective activity against pathogenic protozoa and fungi (Scheme 31).4


Scheme 31

 

1-Boc-pyrrolidinecarbonitrile

Prolyl oligopeptidase inhibitors (Figure 1) might be beneficial in the treatment of patients with cognitive disturbances, as promising experiments with rats and monkeys have shown. Wallen et al. recently presented the synthesis of a very potent inhibitor, which was synthesized using (S)-(–)-1-Boc-pyrrolidinecarbonitrile.5


Figure 1

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Materials

     

References

  1. Aggarwal, V. K. et al. J. Am. Chem. Soc. 2003, 125, 7596.
  2. Bailey, D. J. et al. Tetrahedron: Asymmetry 1997, 8, 149.
  3. Lee, J. et al. Bioorg. Med. Chem. Lett. 2000, 10, 1063.
  4. Ballini, R. et al. J. Org. Chem. 1992, 57, 1316.
  5. Wallén, E. A. A. et al. J. Med. Chem. 2003, 46, 4543.

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