11. The ring closure is carried out at high temperatures ( 200 300 �C, 473 573 K ). 12. A rearrangement reaction of the carbocation follows with ring closure to "'9 " '. 13. In addition, the electronic structure of the transition state differs from that of other conrotary ring closures . 14. It was proposed that the methylene of ( + )-Costunolide is reduced before the second ring closure . 15. For this step, the Schiff base must be heated to ~ 250 �C for the ring closure to occur. 16. The ring closure can even be driven by stereocenters adjacent to the carbon-carbon multiple bond as shown below. 17. Subsequent ring closure leads to the formation of the ?-lactam and the regeneration of the chiral nucleophilic organocatalyst. 18. The mechanism of ring closure is complex, but involves an aldol condensation at C-2 and C-7. 19. This allows for strictosidine s formation under the subsequent ring closure via electrophilic substitution, as shown in the adjacent image. 20. Compound XII was formed from condensation of [ carbonyl-14C-]-2-hydroxy-acetophenone with dimethyl oxylate and ring closure .
