Ongoing Pursuit of Diterpenoid Alkaloids: A Synthetic View

Abstract

The incorporation of nitrogen atoms into policyclic diterpenes has led to one of the most fascinatingg roup of natural products with cage-like structures:d iterpenoid alkaloids. Their singular architectural features and significant bioactivitiesm ade them highly pursued targets amongst the synthetic community over decades. At otal of seven types of diterpenoid alkaloid molecules have been synthesized thus far,a nd the research in this area experiencedanew climax in the past five years. With ab rief overview and summary of the historic achievements, this Focus Review particularly covers the recent,post-2010 advances in the field of diterpenoid alkaloid synthesis, highlighting the utilizationofinnovative synthetic methods and strategies. Despite numerous achievements, there are stillanumber of such alkaloids with differenta nd uniques tructural types waiting to be accomplished, implying that the pursuit is far from ending.

Magnesiate Addition/Ring-Expansion Strategy To Access the 6–7–6 Tricyclic Core of Hetisine-Type C20-Diterpenoid Alkaloids

“…1 Among the many structural classifications that have been established, the hetisine-type C 20 -diterpenoid alkaloids have emerged as compounds of particular interest. They possess one of the most complex frameworks of any of the diterpenoid alkaloids, with a tertiary amine embedded in a caged heptacyclic core (see nominine (1), Figure 1), and are one of the most prominent diterpenoid alkaloid types, with over 120 known members.…”

A Unified Approach for the Assembly of Atisine‐ and Hetidine‐type Diterpenoid Alkaloids: Total Syntheses of Azitine and the Proposed Structure of Navirine C

“…These synthetic campaigns culminated in the completion of formal and total syntheses of a subset of C 20 diterpenoid alkaloids, namely nominine ( 1 ), atisine ( 4 ), isoatisine ( 5 ), isoazitine ( 6 ), dihydroajaconine, gymnandine, spiramines C and D, and cochlearenine . However, most of these synthetic routes require a large number of steps and are restricted to a very particular structure . Two notably short and elegant routes include Gin's total synthesis of nomine (16 steps), and Baran's semisynthesis of isoatisine (13 steps from (−)‐steviol) .…”

Syntheses of Denudatine Diterpenoid Alkaloids: Cochlearenine, N-Ethyl-1α-hydroxy-17-veratroyldictyzine, and Paniculamine

“…13–15 These nitrogen-containing diterpenoids have attracted significant attention from the synthetic community as a result of their diverse biological activity and structural complexity. 16 The earliest synthetic efforts focused on the C 20 alkaloids, resulting in syntheses of atisine ( 1 ), 17,18 garryine, 19,20 veatchine, 20,21 napelline, 22 and nominine ( 2 ). 23 Baran et al demonstrated a unified approach to (−)-methyl atisenoate, its alkaloidal counterpart (−)-isoatisine ( 3 ), and the hetidine skeleton.…”