A strategy for the total synthesis of the structurally unique microbial metabolite echinosporin (1) has been tested. Readily available bromo ester 6 has been converted in a few steps to the TCBOC-protected α-keto ester norbornene system 14. An alternative, shorter, but less reliable route to 14 has also been investigated starting from keto ester 15. Cleavage of the unconjugated olefinic double bond of 14 yielded diacid 21a, which was subsequently converted to a-keto ester 22. Intermediate 22 was transformed to the key enol lactone 24, which possesses the full carbon skeleton and two of the four chiral centers of echinosporin. Further manipulation of lactone 24 gave acetal unsaturated diester 29. Despite considerable effort, 29 could not be converted to the required α-hydroxy ester 31 via dienolate 30. Moreover, mesylate 33, prepared from 29, could not be eliminated to produce 31. Thus, a modified route will have to be developed to construct the α-hydroxy-β,λ-unsaturated cyclopentenyl ester system of 1.
All Science Journal Classification (ASJC) codes
- Organic Chemistry