PROGRESS OF STUDIES ON THE NATURAL CEMBRANOIDS FROM THE SOFT CORAL SPECIES OF SARCOPHYTON GENUS - Medicinal Chemistry of Bioactive Natural Products - page 283

a

HO HO

O

(−)-13-Hydroxy-
neocembrene ( 50 )

(−)-13-Hydroxy-11,12-
Epoxy-neocembrene ( 51 )

Reagents and Conditions: (a) VO(acac) 2 , t-BuOOH, benzene, 23 C, 2 h, 95%.

Scheme 6-22

available trans, trans-farnesol derivative 122 with an overall yield of 42%, by
which the absolute stereochemistry of natural product 181 was assigned unambigu-
ously. 116 The synthesis presented here features a combination of the highly
enantioselective Sharpless epoxidation and CBS reduction for the assembly of
three chiral centers and the macrocyclization of cyanohydrin silyl ether-derived
carbanion alkylation to lead to the 14-membered cembrane cyclic skeleton

(Scheme 6-27).
The spectroscopy data of synthetic 181, as well as the specific rotation, were
found to be identical with that reported for the natural product. The corresponding
acetate of synthetic 181, obtained by direct acylation, was identical with the natural
product in all respects. Therefore, we could conclude that the absolute configuration
of C-11, C-12 of 181 to be (11S,12S).

a b c

O O O

O

O O O

O OH Cl OAc

206 207 208 209

+

d

OH SO 2 Ph

OTHP

137

210

O

THPO

g

f

e

O

OAc OH

O

O

211 212 50
Reagents and Conditions: (a) i. HOCH 2 CH 2 OH, p-TsOH, C 6 H 6 ,reflux, 92%; ii. SeO 2 , t-BuOOH,
CH 2 Cl 2 , rt, 64%; (b) i. (CH 3 ) 2 C ¼ CHCH 2 SO 2 Ph, LDA, THF, 78 C, then added 207; ii. Li, EtNH 2 ,
THF; (c) i. Ac 2 O, Py, 92%; ii. t-BuOCl, silica gel-H, 60%; (d) i. PBr 3 , Py; 2) PhSO 2 Na, 73%; ii. O 3 ,
CH 2 Cl 2 , 78 C, then Me 2 S, 80%; iii. NaBH 4 , MeOH, 0 C, 85%; iv. DHP, p-TsOH, CH 2 Cl 2 , rt, 70%; (e)
i. 50% NaOH, TBAB, 50%; ii. Li-EtNH 2 , THF, 65%; iii. Ac 2 O, Py, 95%; (f) i. p-TsOH, MeOH, 50 C,
82%; ii. PCC, CH 2 Cl 2 , 90%; (g) i. TiCl 4 , Zn-Cu, THF, reflux, 30 h, 38%; ii. K 2 CO 3 , MeOH, 77%.

±

Scheme 6-23