ISSN:
0018-019X
Keywords:
Chemistry
;
Organic Chemistry
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
Notes:
A stereoselective total synthesis of the racemic form of the 2,6-dimethylergolin-8ã-amine derivative III, previously obtained semi-synthetically from lysergic acid, is described. Starting from the commercially available tricyclic lactam 1, the 9,10-didehydroergoline skeleton containing an angular Me group in position 3 (see 18) is built up in several steps applying a Woodward D-ring annelation sequence. The introduction of the 8-amino group is achieved with complete diastereoselectivity to give exclusively the 8ã-derivative 22. Subsequently, a Wagner-Meerwein-type migration of the angular Me group yields the 2-methylated 9,10-didehydroergoline derivative 31. The feasibility of this key transformation was tested on the two model systems 4 and 7 prior to the evaluation of the total synthesis. A stereoselective Birch reduction to the trans-fused ergoline, and deacetylation/acylation conclude the total synthesis of the racemic target compound 34.In addition, the resolution of an early intermediate (see 3) by chromatography on a chiral stationary phase is presented which demonstrates that the described total synthesis could also be used for the preparation of the biologically active (5R,8S,10R)-enantiomer III.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/hlca.19970800709
