choline Receptors 3 Therapeutic use in smoking cessation and neurodegenerational diseases Asymmetric Synthesis of the Lupin Alkaloids Cytisine Sparteine Anagyrine and ID: 483857
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Partial agonist at nicotinic acetyl
choline
Receptors.3 Therapeutic use in: smoking cessation and neurodegenerational diseases.
Asymmetric Synthesis of the Lupin Alkaloids:(-)-Cytisine, (-)-Sparteine, (+)-Anagyrine, and (+)-Thermopsine
Results - HydrogenationThis successful reduction was highly enantioselective with 94.5 % ee and 89 % conversion under optimised conditions.Some over reduction of the pyridone ring was observed (~11 % conv.) ee’s were determined by HPLC
Future Work - Completion of the SynthesisFrom compound 7, completion of the synthesis is known.4 This compound could potentially be reached by the regioselective reduction of imide 6.
References:
PhD AIMS To complete the asymmetric synthesis of: (-)-cytisine, (-)-sparteine, (+)-anagyrine, and (+)-thermopsine To Synthesise desirable cytisine derivatives for pharmaceutical research
1. Burk, M. F.; Gross, J. P. J. Am. Chem. Soc., 19952. Heller, D.; Holz, J. J. Org. Chem. 2001, 66, 68163. Stead, D.; O’Brien, P.; Sanderson, A. J. Organic Letters, 2005, 7, 44594. Gallagher, T.; Gray, D. Angew. Chem. Int. Ed., 2006, 45, 2419
Alexander Bisset1, Martin Wills1, Teyrnon Jones2University of Warwick; 2) AstraZeneca R&D, Charnwood
Background -
Asymmetric Alkene HydrogenationHydrogenation of N-acylamino acrylates (1) is highly selective with catalysts such as [Rh(DuPHOS)COD]BF4 (2)1.Mechanistically, hydrogenation is likely to proceed through the co-ordination mode 32This gave the precedent for the hydrogenation of 5 - a potential (-)-cytisine precursor, which could potentially be reduced in the same way (4).
(-)-cytisine
(-)-sparteine
(+)-anagyrine
(+)-thermopsine
Grounds
for Synthesis
Used in catalysis
as a
c
hiral
bidentate
ligand
4
Although asymmetric syntheses of the alkaloids exist, none have proceeded via asymmetric hydrogenation.
A preliminary study by Akira Shiibashi showed the hydrogenation of 5 successful with high ee.
Some therapeutic uses. Used as precursors in the synthesis of (-)-sparteine analogues.4