Grayanotoxin I
Grayanane
diterpenoids

Exist exclusively in plants of the Ericaceae
family

Possess a unique [5.7.6.5] tetracyclic system
with 7-10 stereogenic centers and dense
arrangement of hydroxy groups

The topic of research in many phytochemical
and pharmacological laboratories(owing to
their various skeletons, complex structures,
and diverse bioactivities)

They exhibit diverse biological properties,
such as analgesic, antinociceptive,
anticancer, antiviral, antifeedant,
insecticidal, toxicity
Grayanotoxin II
Synthesis based on a key biomimetic photo-santonin
rearrangement
• > 39 steps, < 0.0005% overall yield
•
Grayanotoxin III
• 1994 Shirahama and co-workers
achieved an enantioselective total synthesis ( - )
• 38 steps and 0.05% overall yield
• featuring a series of SmI2 mediated stereoselective
cyclizations
Why?
The construction of the [3.2.1] bicyclic skeletons in the total syntheses of
tetracyclic diterpenoids required multistep reaction sequences, which
inevitably maximized functional group manipulations and resulted in
lengthier synthetic routes
Synthesised by a new titanium(III)-mediated
reductive epoxideopening/Beckwith–Dowd
rearrangement process
Rhododendron molle
Rhodomolleins XXII
Rhodomolleins XX
Retrosynthetic analysis
TMSOTf-Trimethylsilyl trifluoromethanesulfonate
TiPS -Triisopropylsilyl
DMDO-dimethyldioxirane
Ts-4-toluenesulfonyl
LDA-lithium diisopropylamine
t-Butyldimethylsilyl
TBAF-tetra-n-butylammonium fluoride