PROGRESS OF STUDIES ON THE NATURAL CEMBRANOIDS FROM THE SOFT CORAL SPECIES OF SARCOPHYTON GENUS - Medicinal Chemistry of Bioactive Natural Products - page 272

OH OAc OAc

a b c

O

OH

91 122 143

SPh

d

O

OH

141 ± 17

Reagents and Conditions: (a) i. Ac 2 O, Py, DMAP, rt, 2 h, 98%; ii. SeO 2 , t-BuOOH, salicyclic acid, rt,
64%; (b) methyl isopropyl ketone, THF, LDA, 78 C, then iodide of 122, 57%; (c) i. K 2 CO 3 , MeOH, rt,
30 min, 95%; ii. n-BuLi, TsCl, then PhSLi, 89%; (d) i. LDA, Dabco, THF, 78 C, 58%; ii. Li-Et-NH 2 ,
78 C, 78%.

Scheme 6-8

C(27) was first isolated as a component of oleoresin of Pinus koraiensis by
Raldugin in 1971, but its structure was not confirmed. 90 In 1978, Vanderah et al.
isolated it from the soft coral Nephthea spp. and established its structure as
(E,E,E,E)-1,7,11-trimethyl-4-isopropyl-1,3,7,11-cyclotetradecatetraene. It was also
found in another soft coral Sarcophyton ehrenbergi afterward. Cembrene C (27)
was synthesized in a trace amount by isomerization of naturally occurring cem-
brene A (59) (Scheme 6-9).
In view of their biological activity and challenging structural features, some total
syntheses of 59 and 27 have been reported.

6.4.2.1 Total Synthesis of Cembrene A
The closure of the macrocyclic ring by means of an intramolecular S N 2 reaction is a
straightforward approach. For example, an intramolecular nucleophilic addition of
sulfur-stabilized carbanion to epoxide was used in the synthesis of nephthenol (40)
and cembrene A (59) from trans,trans-geranyllianlool (144) (Scheme 6-10). 91

base

Cembrene A ( 59 ) Cembrene C ( 27 )

Scheme 6-9