The synthesis of phycopsisenone, a new phenolic secondary metabolite from the sponge Phycopsis sp.

Article abstract of DOI:10.1021/np970394g

A short first total synthesis of phycopsisenone (1) utilizing microwave irradiation-induced aldol condensation and TiCl⁴-catalyzed reaction of silyl enol ether (3) with acetone as key steps has been achieved in 29.4% overall yield.

Full text of DOI:10.1021/np970394g

J . Nat. Prod. 1998, 61, 297-298
297
Th e Syn th esis of P h ycop sisen on e, a New P h en olic Secon d a r y Meta bolite fr om
th e Sp on ge P h ycopsis sp .
G. L. Kad,* Vasundhara Singh, Anupam Khurana, and J asvinder Singh
Department of Chemistry, Panjab University, Chandigarh 160014, India
Received August 19, 1997
A short first total synthesis of phycopsisenone (1) utilizing microwave irradiation-induced aldol
condensation and TiCl -catalyzed reaction of silyl enol ether (3) with acetone as key steps has
4
been achieved in 29.4% overall yield.
Several prenylated aromatic compounds have been
solution (10 mL) in open beaker covered by a watch
glass and subjected to microwave irradiation for 15 min
at a power level of 150 W. The deep red solution was
acidified with 10% HCl solution and extracted with
ether (4 × 25 mL). The combined organic extracts were
dried and evaporated to obtain crude product 2, which
was recrystallized from benzene to afford 2 as yellow
1
isolated from marine flora and fauna and are known
2
to be biologically active. Venkateswarlu et al. inves-
tigated the sponge Phycopsis sp. collected from the
Tuticorin coast, Tamilnadu, India. A CH2Cl2-MeOH
1:1) extract of this organism exhibited antibacterial
activity against E. coli and B. subtilis. One of the
components of this extract was phycopsisenone (1), the
structure of which was assigned on the basis of its
spectroscopic studies.2 We wish to report a simple
synthesis of compound 1 (Scheme 1).
(
solid: mp 102-103 °C (2.15 g, 65%); IR (KBr) ν
max
3450
-1 1
(OH), 1680 (CdO), 1640, 1540 cm ; H NMR δ 2.6 (3H,
s, H-1), 6.2-6.3 (1H, d, H-3, J ) 13.5 Hz), 6.5-6.7 (2H,
d, H-3′ and H-5′, J ) 7 Hz), 7.0-7.4 (3H, m, H-4, H-2′
and H-6′).
Microwave irradiation-induced aldol condensation of
4
-hydroxybenzaldehyde and acetone in aqueous NaOH
1
-[4′-(Tr im eth ylsiloxy)p h en yl]-3-(tr im eth ylsilox-
solution afforded the R,â-unsaturated ketone in 65%
yield. Compound 2 on treatment with trimethylchlo-
rosilane and DBU as a base at 40 °C for 30 min gave
y)bu ta -1,3-d ien e (3). A dry solution of 2 (0.5 g, 3.08
mmol) in CH2Cl2 (10 mL), trimethylchlorosilane (0.86
mL, 6.7 mmol), and 1,8-diazabicyclo[5.4.0]undec-7-ene
3
the enol ether 3. Further condensation of 3 with
(
DBU, 1.12 g, 7.3 mmol) under N2 was stirred at 40 °C
acetone using TiCl44 as the Lewis acid at -78 °C
furnished the title compound 1 after column chroma-
tography using petroleum ether-EtOAc (9:1) in 60%
yield (29.4% overall yield). The spectral data of the
synthetic sample agree well with those reported in the
for 2 h. The mixture was diluted with hexane (10 mL),
washed successively with 1% HCl (2 × 10 mL) and 5%
NaHCO3 (2 × 10 mL), dried, evaporated, and distilled
to give 3 (0.37 g; 39%): IR (neat) νmax 1660, 1635, 1640,
-1
1
1
(
560 cm ; H NMR δ 0.17 (18H, s, Si(CH3)3 × 2), 4.2
2
literature.
2H, d, H-4, J ) 1.7 Hz), 6.2-6.3 (1H, d, H-2, J ) 13.5
Hz), 6.5-6.7 (2H, d, H-3′ and H-5′, J ) 7 Hz), 7.0-7.4
(3H, m, H-1, H-2′ and H-6′).
Exp er im en ta l Section
5
-Hyd r oxy-1-(4′-h yd r oxyp h en yl)-5-m eth yl-1-h ex-
Gen er a l Exp er im en ta l P r oced u r es. 1H and 13
C
en -3-on e (1). Acetone (0.1 mL, 5 mmol) and anhydrous
CH2Cl2 solution (10 mL) were cooled to -78 °C under
N2, and TiCl4 (0.17 mL, 5 mmol) was added. Silyl enol
ether 3 (0.355 mg, 5 mmol) was added dropwise to this
solution and stirred for 3 h at -78 °C followed by
stirring at room temperature for 16 h. The dark red
solution was quenched with aqueous NaHCO3, stirred
for 5 h, and then extracted with ether (5 × 10 mL). The
ether extract was dried and evaporated to give a crude
product that was purified by column chromatography
using petroleum ether-EtOAc (9:1) as an eluent to give
a pure colorless solid 1 (0.153 mg, 60%): mp 135 °C; IR
NMR spectra were recorded in CDCl3 on a 300 MHz
Bruker spectrometer using TMS as internal standard.
IR spectra were recorded on a Perkin-Elmer 337 spec-
trophotometer. Mass spectra were determined on VG
7
0S with an 11-250 J + data system. A BPL domestic
microwave oven with a power output of 700 W was used.
Unless otherwise stated, all organic extracts were dried
over anhydrous sodium sulfate. Silica gel (ASC, Bom-
bay) impregnated with calcium sulfate was used for
TLC.
4
-(4′-Hydr oxyph en yl)bu t-3-en -2-on e (2). To a clear
solution of 4-hydroxybenzaldehyde (2.5 g, 20.4 mmol)
in 10% NaOH (7 mL) was added acetone (7.0 g, 120.6
mmol) at 25 °C followed by remaining 10% NaOH
-
1
(
KBr) νmax 3450 (OH), 1680 (CdO), 1640, 1560 cm
H NMR (CDCl3) δ 1.3 (6H, s), 2.8 (2H, s, H-4), 6.5 (1H,
;
1
d, H-2, J ) 13.5 Hz) 6.8 (2H, d, H-3′ and H-5′, J ) 7
Hz), 7.45 (2H, d, H-2′ and H-6′, J ) 7 Hz), 7.5 (1H, d,
*
To whom correspondence should be addressed. Tel.: 0172-541435.
1
3
Fax: 0172-541409.
H-1, J ) 13.5 Hz); C NMR (CDCl3) δ 201.7, 158.4,
S0163-3864(97)00394-7 CCC: $15.00
© 1998 American Chemical Society and American Society of Pharmacognosy
Published on Web 02/03/1998

2
98 J ournal of Natural Products, 1998, Vol. 61, No. 2
Notes
Sch em e 1. Synthesis of Phycopsisenone
1
43.7, 130.5, 126.7, 124.5, 116.1, 70.6, 50.5, 29.4, 29.2;
Refer en ces a n d Notes
+
EIMS (70 ev) m/z [M ] 220, 202, 162, 147 (100), 107;
anal. C 70.70%, H 7.21%, calcd for C13H16O3, C 70.88%,
H 7.32%.
(1) Faulkner, D. J . Nat. Prod. Rep. 1984, 1, 251.
(2) Venkateswarlu, Y.; Farooq Biabani, M. A.; Rao, J . V. J . Nat.
Prod. 1995, 58, 269-270.
(
3) Taniguchi, Y.; Inanaga, J .; Yamaguchi, M. Bull. Chem. Soc. J pn.
981, 54, 3229-3230.
4) Chan, T. N.; St o¨ ssel, D. J . Org. Chem. 1986, 51, 2423-2428.
1
(
Ack n ow led gm en t. The authors are thankful to
UGC, New Delhi, for financial support.
NP970394G