2018 Springer Science+Business Media, LLC
Chemistry of Natural Compounds, Vol. 54, No. 3, May, 2018
STEREOSELECTIVE SYNTHESIS OF THE ANTILEUKEMIC
SESQUITERPENE (+)-CAPARRATRIENE FROM L-MENTHOL
AND TIGLIC ALDEHYDE
V. A. Vydrina, A. A. Kravchenko, M. P. Yakovleva,*
N. M. Ishmuratova, and G. Yu. Ishmuratov
A stereoselective synthesis of natural (+)-caparratriene was developed starting from commercially available
L-menthol and tiglic aldehyde. The key step was a Wittig reaction of the latter with the triphenylphosphorane
generated from (R)-(–)-citronellyl bromide. (+)-Caparratriene as a mixture (4:1) of 2E,4E- and
2E,4Z-stereoisomers is a known anticancer agent.
Keywords: (+)-caparratriene, L-menthol, tiglic aldehyde, Wittig reaction, (R)-(–)-citronellyl bromide.
The sesquiterpenoid 3,7R,11-trimethyldodeca-2E,4E,10-triene [(+)-caparratriene, 1] was isolated from the Colombian
tree Ocotea caparrapi and possessed significant pharmacological activity including antileukemic . It was prepared previously
in racemic  and optically active forms  using (r)- and (+)-citronellal and tiglic aldehyde (2) as starting materials. Various
modifications of the Wittig reaction were most often used in the key step of forming the (2E,4E)-diene fragment of the target
caparratriene (1). The carbon skeleton of tiglic aldehyde (2) was incorporated after converting it through the corresponding
alcohol, bromide, and phosphonium salt into the allylic triphenylphosphorane.
A new synthetic scheme for an analog of 1, 3,7R,11-trimethyldodeca-2E,4,10-triene [(2E,4)-1], was elaborated starting
from L-menthol (3) and tiglic aldehyde (2). It was based on Wittig olefination using starting conjugated aldehyde 2 as the
carbonyl component. The required ylide was generated from triphenylphosphonium salt 4 of (R)-(–)-citronellyl bromide (5)
using n-butyllithium. In turn, optically pure bromide 5 was obtained via chemo- and regioselective transformations of ketoalcohol 6,
the preparation of which from L-menthol (3) in four steps through (–)-menthyl lactone was reported earlier by us .
Further transformations aimed at (R)-(–)-citronellyl bromide (5) included regiospecific Baeyer–Villager oxidation of
tetrahydropyranyl (THP) derivative 7 of hydroxyketone 6, one-pot low-temperature (–70°C) hydride reduction of the resulting
Ufa Institute of Chemistry, Russian Academy of Sciences, 71 Prosp. Oktyabrya, Ufa, 450054; e-mail: email@example.com.
Translated from Khimiya Prirodnykh Soedinenii, No. 3, May–June, 2018, pp. 391–393. Original article submitted
November 14, 2017.
O; b. m-CPBA; c. 1. DIBAH/THF, –70qC, 2. Pr
Li; d. PPTS/Et
O; e. PBr
/Py; f. PPh
; g. 1. Bu
Li/THF, 2. 2, 20qC
(DHP = 3,4-dihydro-2H-pyran; m-CPBA = meta-chloroperbenzoic acid; DIBAH = diisobutylaluminum hydride; PPTS = pyridinium