ISSN:
0018-019X
Schlagwort(e):
Chemistry
;
Organic Chemistry
Quelle:
Wiley InterScience Backfile Collection 1832-2000
Thema:
Chemie und Pharmazie
Notizen:
The preparation of an analogue 3a of the acetylcholinesterase inhibitor, huperzine A (1), is described in which the pyridinone moiety of the natural product is replaced with a thiazolone moiety. The synthesis started from cyclohexane-1,4-dione monoethylene ketal (7) by first annulating the thiazole ring using the Gewald protocol (→ 8; Scheme 1) and then constructing the bicyclo[3.3.1]nonane substructure using our previously described Michael addition/aldol condensation methodology (Scheme 3). The central problem was the protection of the thiazolone carbonyl group; only the 2-unsubstituted thiazole survived the reaction conditions of the first half of the synthesis. Refunctionalization was later effected by lithiation and subsequent chlorination with hexachloroethane (30→31). Compound 3a was ineffective in the acetylcholinesterase inhibition assay in concentrations up to 14 μM.
Materialart:
Digitale Medien
URL:
http://dx.doi.org/10.1002/hlca.19940770508
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