Functionalized derivatives of manoyl oxide are labdane-type diterpenoids isolated from
natural source and possessing significant biological properties [1, 2].
The current report presents the results on the synthesis of some C-15 functionalized
derivatives of manoyl- and 13-epi-manoyl oxide (1a) and (2a), obtained from Horner-
Wadsworth-Emmons’s (HWE) reaction. As starting material for HWE reaction some
bisnorlabdanic keto-derivatives (3a-3c), readily available from either commercial (-)-sclareol
(4a) or its diacetate (4b), were used according to the Scheme 1 given below.

Scheme 1
Reagents and conditions: (a) KMnO4, Me2CO, r.t., 5 h, 84%; (b) Ac2O, DCM, 4-DMAP, r.t, 48 h, r.t.
90%; (c) TBDMSCl, Py, r.t., 48 h, 25 %; (d) (MeO)2P(O)CH2CO2Me, C6H6, MeONa, reflux, 3 h; (e) 10%
KOH, EtOH, reflux, 3 h, 91%.
The transformation of ketones (3a-3c) by means of HWE procedure was the key step in the
present communication. Reaction yields varied from 72% to 80%, depending on the substrate
which was used. The hydroxy ketone (3a) reacted exclusively with the selective formation of the
compound (1a) (72%). Both ketones (3b) and (3c) gave a mixture (~2:1) of substances (1a) and
(2a). Saponification of esters (1a) and (2a) with an ethanolic solution of potassium hydroxide led
to the formation of acids (1b) and (2b), which are the enantiomers of gomeric (5a) and 13-epigomeric
(5b) acids, isolated from the medicinal plant Sideritis gomerae [3]. The structure and
stereochemistry of the newly synthesized compounds were established on the basis of their
spectral data.
References:
1. Frija, L. M. T.; Frade, R. F. M.; Afonso, C. A. M. Chem. Rev., 2011, 111, 4418–4452.
2. Hanson, J. R. Nat. Prod. Rep., 2013, 30, 1346-1356 and privies articles of this series.
3. González, A. G.; Fraga, B. M.; Hernández, M. G.; Larruga, F.; Luis, J. Phytochemistry, 1975, 14
(12), 2655-2656.