Further studies on CAB approach toward chemical conversion of C₁₉-diterpenoid alkaloids to taxoids: synthesis of the vital intermediate C-nor-aconanone

Abstract

In the title study, the synthesis of the vital intermediate C-nor-aconanone (3) from 4 was completed through 11 steps, mainly including semipinacol rearrangement, formation of the imines by the treatment of 10 or 20 with NBS, the cleavage of N–C(19) bonds in 11 or 21 by treatment with m-CPBA and subsequently with LTA, as well as the rupture of the N–C(17) bonds in 22 by a modified Nef reaction (NaH/t-BuOH → KMnO₄/H₂O). One-pot procedure was successfully developed starting from 11 or 21 to afford the N,19-seco-C-nor product 15 or 22, respectively, in reasonably good yields.

Keywords:

• N,19-seco-C₁₉-diterpenoid alkaloid
• N,17-seco-C₁₉-diterpenoid alkaloid
• Aconane-type diterpene
• semipinacol rearrangement
• imine
• m-CPBA–LTA oxidation

Acknowledgements

Financial support for this research was provided from the National Natural Science Foundation of China (no. 30472075) and the Excellent Ph.D. Dissertation Foundation of China (no. 200367). We graciously acknowledge Prof. Xiao-Tian Liang of Institute of Materia Medica, Chinese Academy of Medical Sciences, China, for helpful discussion on the subject and inspection of this manuscript.