Synthesis and antialgal activity of dihydrophenanthrenes and phenanthrenes II: Mimics of naturally occurring compounds in Juncus effusus

Article abstract of DOI:10.1023/A:1005624304413

9,10-Dihydrophenanthrenes and phenanthrenes, mimics of natural compounds with strong antialgal activity, have been synthesized through cross-coupling by zerovalent Ni of 1-(2-iodo-5-methoxy)-phenylethanol or 2-iodo-5-methoxyacetophenone with iodoxylenes. The synthetic compounds had a hydroxyl or a methoxyl group at C-2 and two methyls in the C ring. Assays on the green alga Selenastrum capricornutum showed that all the compounds, except 2-methoxy-5,7-dimethylphenanthrene, caused strong inhibition of algal growth at 10^-4 M. 2-Hydroxy-7,8-dimethyl-9,10-dihydrophenanthrene and 2-methoxy-5,6-dimethylphenanthrene fully inhibited growth at 10^-5 M.

Full text of DOI:10.1023/A:1005624304413

Journal of Chemical Ecology, Vol. 27, No. 2, 2001
SYNTHESIS AND ANTIALGAL ACTIVITY OF
DIHYDROPHENANTHRENES AND PHENANTHRENES II:
MIMICS OF NATURALLY OCCURRING
COMPOUNDS IN Juncus effusus
1
2
1
3
M. DELLAGRECA, A. FIORENTINO, P. MONACO, G. PINTO,
1
,
1
L. PREVITERA, * and A. ZARRELLI
1Dipartimento di Chimica Organica e Biologica
Universit a` Federico II
Via Mezzocannone 16, I-80134 Naples, Italy
2Dipartimento di Scienze della Vita
II Universit a` di Napoli
Via Arena, I-84100 Caserta, Italy
3Dipartimento di Biologia Vegetale
Universita
` Federico II
Via Foria 223, I-80139 Naples, Italy
(Received November 15, 1999; accepted September 30, 2000)
Abstract—9,10-Dihydrophenanthrenes and phenanthrenes, mimics of natural
compounds with strong antialgal activity, have been synthesized through cross-
coupling by zerovalent Ni of 1-(2-iodo-5-methoxy)-phenylethanol or 2-iodo-5-
methoxyacetophenone with iodoxylenes. The synthetic compounds had a hydro-
xyl or a methoxyl group at C-2 and two methyls in the C ring. Assays on the
green alga Selenastrum capricornutum showed that all the compounds, except
2
-methoxy-5,7-dimethylphenanthrene, caused strong inhibition of algal growth
4
at 10 M. 2-Hydroxy-7,8-dimethyl-9,10-dihydrophenanthrene and 2-methoxy-
,6-dimethylphenanthrene fully inhibited growth at 10 5 M.
5
Key Words—Juncus effusus, phenanthrenes, 9,10-dihydrophenanthrenes,
cross-coupling algicides, Selenastrum capricornutum.
INTRODUCTION
We reported in a previous paper (DellaGreca et al., 2000) the synthesis of 9,10-
dihydrophenanthrenes 1a–1l and phenanthrenes 2a–2l, mimics of natural com-
*
To whom correspondence should be addressed.
2
57
0
098-0331
/
01
/
0200-0257$19.50 0  2001 Plenum Publishing Corporation
/

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DELLAGRECA ET AL.
pounds isolated from the wetland plant, Jancus effusus (DellaGreca et al., 1992,
993, 1995a,b, 1997). The compounds have the common feature of a hydroxyl
1
or a methoxyl group at the C-2 position of the A ring, while a methyl group
is located at different positions of the C ring. Synthesis was based on cross-
coupling of 1-(2-iodo-5-methoxy)-phenylethanol (3) with the three isomeric
iodotoluenes. The compounds, except 7-methyl-2-methoxyphenanthrene (2g),
showed strong antialgal activity in assays of the freshwater green alga Selenas-
4
trum capricornutum at 10 M concentration. Most of them also retained strong
5
activity at 10 M.
In pursuing the study of the structure–activity relationship, we have now
synthesized all the isomeric phenanthrenes and 9,10-dihydrophenanthrenes with
a hydroxyl or a methoxyl at C-2 bearing two methyls in the C ring. The synthesis
was based on the cross-coupling of iodoarenes by zerovalent nickel (Semmel-
hack et al., 1981).
METHODS AND MATERIALS
Chemicals. 3-Iodo-4-methylbenzoic acid and iodobenzenes were obtained
commercially (Aldrich). 1-(2-Iodo-5-methoxy)-phenylethanol (3) was prepared
as reported by DellaGreca et al. (2000).
General Experimental Procedures. NMR spectra were recorded at 400
1
13
MHz for H and 100 MHz for C on a Bruker AC 400 spectrometer in CDCl3
solutions. One-bond and long-range H-C COSY experiments were performed
with the XHCORR microprogram with delays corresponding to JC, H 160 Hz
and 8 Hz, respectively. HPLC was performed on a Varian Vista 5500 with a UV
detector.
Synthesis of 2-Hydroxy-6,7-dimethyl-9,10-dihydrophenanthrene (1t), 2-
Hydroxy-7,8-dimethyl-9,10-dihydrophenanthrene (1x), 2-Hydroxy-6,7-dimethyl-
phenanthrene (2t), and 2-Hydroxy-7,8-dimethylphenanthrene (2x). To a 50-ml
three-necked flask, zinc dust (392 mg, 6 mmol washed with 2 N HCl, H2O,
EtOH, Me2CO, Et2O, and dried in an oven at 120 C), NiCl2 (784 mg, 6 mmol),
PPh3 (6.3 g, 24 mmol), and dry DMF (10 ml) were added. The mixture was
warmed at 40 C under N2 and stirred for 1 hr. A solution of 3 (834 mg, 3
mmol) and iodo-3,4-dimethylbenzene (696 mg, 3 mmol) in dry DMF (5 ml)
was added at once, and the reaction mixture was kept at 40 C for 6 hr. Then
2
N NH4OH was added and the mixture was extracted with Et2O. After evap-
oration the residue was chromatographed on silica gel (benzene–Et2O 19 : 1) to
1
afford biphenyl 5b (360 mg, 1.4 mmol, 47%): H NMR d 7.21 (1H, d, J 2.3
Hz, H-3), 6.84 (1H, dd, J 2.3 and 8.4 Hz, H-5), 7.15 (1H, d, J 8.4 Hz, H-6),
7
.05 (1H, d, J 2.3 Hz, H-2
.3 and 8.5 Hz, H-6 ), 5.00 (1H, q, J 6.4 Hz, H-7), 1.39 (3H, d, J 6.4 Hz,
H-8), 3.86 (3H, s, OMe), 2.30 (3H, s, Me), 2.31 (3H, s, Me).
′ ′
), 7.16 (1H, d, J 8.5 Hz, H-5 ), 7.01 (1H, dd, J
2
′

MIMICS OF Juncus COMPOUNDS
259
To a solution of 5b (360 mg, 1.4 mmol) in dry xylene (1 ml), I2 (20 mg, 0.08
mol) was added and the mixture was kept at 140 C for 6 hr. Addition of 10%
aq NaHSO3 and extraction with Et2O gave a residue that was chromatographed
1
on silica gel (hexane) to give 6b (265 mg, 1.1 mmol, 80%): H NMR d 7.24
(
1H, d, J 2.2 Hz, H-3), 6.94 (1H, dd, J 2.2 and 8.4 Hz, H-5), 7.19 (1H, d, J
.4 Hz, H-6), 7.21 (1H, d, J 2.4 Hz, H-2 ), 7.28 (1H, d, J 8.4 Hz, H-5 ),
.16 (1H, dd, J 2.4 and 8.5 Hz, H-6 ), 6.76 (1H, dd, J 10.5 and 17.6 Hz,
8
′
′
7
′
H-7), 5.24 (1H, dd, J 1.8 and 10.5 Hz, H-8), 5.75 (1H, dd, J 1.8 and 17.6
Hz, H-8), 3.91 (3H, s, OMe), 2.37 (6H, s, Me).
A sample of 6b (130 mg, 0.55 mmol) in dry benzene (6.5 ml) in a Pyrex
flask was irradiated under an air atmosphere with a 450-W Hanovia lamp at
room temperature for 30 min with magnetic stirring to give a mixture of 2s and
2
w (63 mg, 0.30 mmol, 54%) along with unreacted 6b (52 mg). 2s and 2w were
1
separated by HPLC-NH2 (hexane–isopropyl ether 98.5 : 1.5) 2s (28 mg) had: H
NMR d 7.22–7.36 (2H, m, H-1 and H-3), 8.60 (1H, d, J 9.1 Hz, H-4), 8.36
(
7
1H, s, H-5), 7.63 (1H, s, H-8), 7.63 (1H, d, J 7.4 Hz, H-9), 7.48 (1H, d, J
.4 Hz, H-10), 3.97 (3H, s, OMe), 2.55 (3H, s, Me), 2.49 (3H, s, Me); 13C NMR
d 117.0 (C-1), 157.2 (C-2), 108.9 (C-3), 124.6 (C-4), 122.8 (C-5), 134.9 (C-6),
1
1
33.8 (C-7), 129.5 (C-8), 125.8 (C-9), 127.3 (C-10), 132.6 (C-1a), 125.9 (C-4a),
27.9 (C-5a), 133.9 (C-8a) 55.6 (OMe), 20.8 (Me), 22.9 (Me). Compound 2w
1
(27 mg) had: H NMR d 7.22–7.36 (2H, m, H-1 and H-3), 8.62 (1H, d, J 9.3
Hz, H-4), 8.39 (1H, d, J 9.3 Hz, H-5), 7.71 (1H, d, J 9.3 Hz, H-6), 8.02
1H, d, J 8.4 Hz, H-9), 7.57 (1H, d, J 8.4 Hz, H-10), 3.98 (3H, s, OMe),
.55 (3H, s, Me), 2.83 (3H, s, Me); 13C NMR d 117.3 (C-1), 157.3 (C-2), 108.5
C-3), 124.3 (C-4), 120.0 (C-5), 128.9 (C-6), 133.9 (C-7), 136.1 (C-8), 123.8 (C-
), 126.4 (C-10), 132.7 (C-1a), 126.6 (C-4a), 128.1 (C-5a), 129.8 (C-8a), 55.6
(
2
(
9
(
OMe), 20.1 (Me), 21.0 (Me).
To a solution of 2s (26 mg, 0.12 mmol) in dry CH2Cl2 (1.5 ml) cooled
at 70 C, BBr3 (100 ml) was added. Addition of 1 N NaHCO3 after 3 hr and
extraction with CHCl3 gave a residue that was purified by preparative TLC
1
(
hexane–Et2O 1 : 1) to give 2t (18 mg, 0.08 mmol, 70%): H NMR d 7.21 (1H,
d, J 2.1 Hz, H-1), 7.19 (1H, dd, J 2, 1 and 9.2 Hz, H-3), 8.56 (1H, d, J
.2 Hz, H-4), 8.34 (1H, s, H-5), 7.60 (1H, s, H-8), 7.62 (1H, d, J 7.4 Hz,
H-9), 7.46 (1H, d, J 7.4 Hz, H-10), 2.52 (3H, s, Me), 2.45 (3H, s, Me); 13
NMR d 116.6 (C-1), 153.8 (C-2), 111.7 (C-3), 124.9 (C-4), 122.7 (C-5), 135.0
9
C
(
(
C-6), 133.8 (C-7), 129.5 (C-8), 125.4 (C-9), 127.5 (C-10), 132.7 (C-1a), 125.8
C-4a), 128.0 (C-5a), 133.5 (C-8a) 20.8 (Me), 21.1 (Me).
To a solution of 2w (25 mg, 0.12 mmol) in dry CH2Cl2 (1.5 ml) cooled
at 70 C, BBr3 (100 ml) was added. Addition of 1 N NaHCO3 after 3 hr and
extraction with CHCl3 gave a residue that was purified by preparative TLC
1
(
hexane–Et2O 1 : 1) to give 2x (17 mg, 0.09 mmol, 70%): H NMR d 7.21 (1H,
d, J 2.3 Hz, H-1), 7.19 (1H, dd J 2.3 and 9.2 Hz), 8.58 (1H, d, J 9.2 Hz,

2
60
DELLAGRECA ET AL.
H-4), 8.37 (1H, d, J 9.3 Hz, H-5), 7.70 (1H, d, J 9.3 Hz, H-6), 8.00 (1H, d,
8.4 Hz, H-9), 7.52 (1H, d, J 8.4 Hz, H-10), 2.52 (3H, s, Me), 2.65 (3H,
J
1
3
s, Me); C NMR d 116.9 (C-1), 154.0 (C-2), 112.0 (C-3), 124.6 (C-4), 119.9
(
(
C-5), 128.9 (C-6), 133.9 (C-7), 136.2 (C-8), 124.0 (C-9), 126.1 (C-10), 133.1
C-1a), 126.4 (C-4a), 128.1 (C-5a), 129.8 (C-8a), 20.1 (Me), 20.8 (Me).
To an EtOH solution (4.8 ml) of 2s (26 mg, 0.12 mmol), NaBH4 (0.3 mmol)
and Et3N (1.2 mmol) were added. The reaction mixture was irradiated for 2.5
hr with a Hanovia 450-W lamp and then HCl 10% was added. CHCl3 extrac-
tion gave a crude product, which was chromatographed by preparative TLC
1
(
(
hexane–benzene 9 : 1) to give 1s (13 mg, 0.06 mmol, 50%): H NMR d 6.72
1H, d, J 2.3 Hz, H-1), 6.88 (1H, dd, J 2.3 and 8.4 Hz, H-3), 7.72 (1H, d,
J
8.2 Hz, H-4), 7.03 (1H, s, H-5), 7.49 (1H, s, H-8), 2.83 (4H, brs, H-9 and
1
3
H-10), 3.85 (3H, s, OMe) 2.33 (3H, s, Me), 2.28 (3H, s, Me); C NMR d 112.2
(
(
(
C-1), 159.1 (C-2), 113.5 (C-3), 124.5 (C-4), 124.3 (C-5), 134.9 (C-6), 134.9
C-7), 129.4 (C-8), 28.6 (C-9), 29.8 (C-10), 137.9 (C-1a), 127.9 (C-4a), 138.9
C-5a), 132.0 (C-8a), 55.3 (OMe), 19.7 (Me), 19.4 (Me).
BBr3 (50 ml) treatment of 1s (10 mg, 0.05 mmol) in dry CH2Cl2 (1 ml) at
1
7
0 C for 3 hr gave 1t (7 mg, 0.03 mmol): H NMR d 6.74 (1H, d, J 2.2 Hz,
H-1), 6.78 (1H, dd, J 2.2 and 8.4 Hz, H-3), 7.63 (2H, d, J 8.4 Hz, H-4), 7.03
(
1H, s, H-5), 7.47 (1H, s, H-8), 2.81 (4H, brs, H-9 and H-10), 2.32 (3H, s, Me),
2
4
1
.28 (3H, s, Me); 13C NMR d 113.7 (C-1), 154.1 (C-2), 114.9 (C-3), 124.8 (C-
), 124.3 (C-5), 135.0 (C-6), 135.0 (C-7), 129.4 (C-8), 28.5 (C-9), 29.5 (C-10),
37.8 (C-1a), 127.7 (C-4a), 139.2 (C-5a), 132.0 (C-8a), 19.7 (Me), 19.4 (Me).
Photoreduction of 2w (25 mg, 0.12 mmol), as described for 2s, gave 1w (11
1
mg, 0.06 mmol, 50%): H NMR d 6.79 (1H, d, J 2.4 Hz, H-1), 6.84 (1H, dd,
J
2.4 and 8.5 Hz, H-3), 7.66 (1H, d, J 8.5 Hz, H-4), 7.49 (1H, d, J 8.1 Hz,
H-5), 7.09 (1H, d, J 8.1 Hz, H-6), 2.85 (4H, brs, H-9 and H-10), 3.84 (3H, s,
OMe) 2.34 (3H, s, Me), 2.26 (3H, s, Me); 13C NMR d 112.3 (C-1), 158.6 (C-2),
113.0 (C-3), 125.0 (C-4), 120.6 (C-5), 128.1 (C-6), 134.9 (C-7), 134.8 (C-8),
2
5
5.3 (C-9), 29.4 (C-10), 135.1 (C-1a), 128.1 (C-4a), 138.6 (C-5a), 132.2 (C-8a),
5.3 (OMe), 15.4 (Me), 20.8 (Me).
Demethylation by BBr3 of 1w (10 mg, 0.06 mmol) gave 1x (6 mg, 0.04
1
mmol, 67%): H NMR d 6.72 (1H, d, J 2.4 Hz, H-1), 6.77 (1H, dd, J 2.4
and 8.5 Hz, H-3), 7.61 (1H, d, J 8.5 Hz, H-4), 7.49 (1H, d, J 8.1 Hz, H-5),
7
2
4
1
.11 (1H, d, J 8.1 Hz, H-6), 2.84 (4H, brs, H-9 and H-10), 2.36 (3H, s, Me),
.28 (3H, s, Me); 13C NMR d 113.7 (C-1), 154.6 (C-2), 114.4 (C-3), 125.3 (C-
), 120.6 (C-5), 128.1 (C-6), 134.9 (C-7), 135.2 (C-8), 25.2 (C-9), 29.5 (C-10),
35.2 (C-1a), 128.4 (C-4a), 138.7 (C-5a), 132.3 (C-8a), 15.4 (Me), 20.8 (Me).
Synthesis of 2-Hydroxy-6,8-dimethyl-9,10-dihydrophenanthrene (1v) and 2-
Hydroxy-6,8-dimethylphenanthrene (2v). A solution of 3 (3 mmol) and iodo-3,5-
dimethylbenzene (3 mmol) in dry DMF (5 ml) was added to the mixture of the
active nickel complex prepared as reported above. Work-up after 9 hr at 35 C

MIMICS OF Juncus COMPOUNDS
261
and chromatography on silica gel (benzene–Et2O 19 : 1) gave biaryl 5a (273 mg,
1
1
2
.1 mmol, 37%): H NMR d 7.24 (1H, d, J 2.2 Hz, H-3), 6.86 (1H, dd, J
.2 and 8.3 Hz, H-5), 7.08 (1H, d, J 8.3 Hz, H-6), 6.92 (3H, d, J 2.1 Hz,
′ ′ ′
H-2 and H-4 ) 7.01 (1H, brs, H-6 ), 5.01 (1H, q, J 6.2 Hz, H-7), 1.41 (3H,
d, J 6.2 Hz, H-8), 3.86 (3H, s, OMe), 2.38 (6H, s, Me).
To a solution of 5a (270 mg, 1.1 mmol) in dry xylene (1 ml), I2 (20 mg,
0
.08 mol) was added and the mixture was kept at 140 C for 6 hr. Work-up as
1
for 6b gave 6a (212 mg, 0.88 mmol, 80%): H NMR d 7.30 (1H, d, J 2.2 Hz,
H-3), 6.98 (1H, dd, J 2.2 and 8.4 Hz, H-5), 7.32 (1H, d, J 8.4 Hz, H-6),
7
1
1
′ ′ ′
.09 (2H, brs, H-2 and H-6 ), 7.18 (1H, brs, H-4 ), 6.88 (1H, dd, J 10.6 and
7.5 Hz, H-7), 5.32 (1H, dd, J 1.8 and 10.6 Hz, H-8), 5.83 (1H, dd, J-1.8 and
7.5 Hz, H-8), 3.98 (3H, s, OMe), 2.49 (6H, s, Me).
Photocyclization of 6a (100 mg, 0.4 mmol) in an Ar atmosphere for 1 hr
gave 2-methoxy-6,8-dimethyl-9,10-dihydrophenanthrene (1u) (74 mg, 0.3 mmol,
1
7
5%): H NMR d 6.81 (1H, d, J 2.4 Hz, H-1), 6.88 (1H, dd, J 2.4 and 8.5 Hz, H-
), 7.71 (1H, d, J 8.5 Hz, H-4), 6.95 (1H, d, J 2.3 Hz, H-5), 7.41 (1H, d, J 2.3
3
Hz, H-7), 2.82 (4H, brs, H-9 and H-10), 3.86 (3H, s, OMe) 2.37 (3H, s, Me), 2.33
1
3
(
3H, s, Me); C NMR d 112.3 (C-1), 158.9 (C-2), 113.2 (C-3), 125.3 (C-4), 121.8
(
C-5), 135.2 (C-6), 129.4 (C-7), 134.4 (C-8), 24.5 (C-9), 29.4 (C-10), 135.6 (C-
1
a), 128.0 (C-4a), 138.9 (C-5a), 132.0 (C-8a), 55.3 (OMe), 21.3 (Me), 19.7 (Me).
BBr3 demethylation of 1u (30 mg, 0.18 mmol) gave 1v (20 mg, 0.12 mmol, 68%):
1
H NMR d 6.72 (1H, d, J 2.5 Hz, H-1), 6.78 (1H, dd, J 2.5 and 8.3 Hz, H-3),
7
.64 (1H, d, J 8.3 Hz, H-4), 6.93 (1H, d, J 2.3 Hz, H-5), 7.41 (1H, d, J 2.3
1
3
Hz, H-7), 2.80 (4H, brs, H-9 and H-10), 2.39 (3H, s, Me), 2.33 (3H, s, Me);
C
NMR d 113.7 (C-1), 154.7 (C-2), 114.6 (C-3), 125.4 (C-4), 121.6 (C-5), 135.1 (C-
6
1
), 129.4 (C-7), 134.8 (C-8), 24.3 (C-9), 29.1 (C-10), 135.5 (C-1a), 128.1 (C-4a),
39.2 (C-5a), 131.9 (C-8a), 21.2 (Me), 19.7 (Me).
Photocyclization of 6a (100 mg, 0.4 mmol) in the presence of atmospheric
1
oxygen gave 2u (70 mg, 0.3 mmol, 75%): H NMR d 7.22–7.36 (2H, m, H-1
and H-3), 8.52 (1H, d, J 9.2 Hz, H-4), 8.30 (1H, d, J 1.9 Hz, H-5), 7.22
(
1H, d, J 1.9 Hz, H-7), 7.91 (1H, d, J 7.4 Hz, H-9), 7.57 (1H, d, J 7.4
1
3
Hz, H-10), 3.98 (3H, s, OMe), 2.72 (3H, s, Me), 2.52 (3H, s, Me); C NMR
d 117.0 (C-1), 158.2 (C-2), 108.3 (C-3), 124.6 (C-4), 120.1 (C-5), 134.7 (C-6),
1
1
23.5 (C-7), 135.9 (C-8), 125.3 (C-9), 128.7 (C-10), 133.3 (C-1a), 124.8 (C-4a),
27.8 (C-5a), 130.7 (C-8a), 55.4 (OMe), 22.0 (Me), 19.8 (Me). Demethylation
1
of 2u (35 mg, 0.2 mmol) by BBr3 gave 2v (26 mg, 0.14 mmol, 70%): H NMR
d 7.22–7.36 (2H, m, H-1 and H-3), 8.61 (1H, d, J 9.2 Hz, H-4), 8.28 (1H, d,
J
7
1.9 Hz, H-5), 7.22 (1H, d, J 1.9 Hz, H-7), 7.91 (1H, d, J 7.4 Hz, H-9),
.58 (1H, d, J 7.4 Hz, H-10), 2.71 (3H, s, Me), 2.57 (3H, s, Me); 13C NMR
d 117.1 (C-1), 153.0 (C-2), 111.5 (C-3), 124.9 (C-4), 120.2 (C-5), 134.9 (C-6),
1
1
23.5 (C-7), 136.0 (C-8), 125.3 (C-9), 128.7 (C-10), 133.7 (C-1a), 124.6 (C-4a),
27.8 (C-5a), 130.4 (C-8a), 22.2 (Me), 20.0 (Me).

2
62
DELLAGRECA ET AL.
Synthesis of 2-Hydroxy-5,6-dimethyl-9,10-dihydrophenanthrene (1n) and 2-
Hydroxy-5,6-dimethylphenanthrene (2n). 2-Iodo-5-methoxyacetophenone (830
mg, 3 mmol), obtained by reaction of equimolar amounts of 3-methoxyacetophe-
none, I2, CF3COOAg, and iodo-2,3-dimethylbenzene (696 mg, 3 mmol) were
added to a flask containing active Ni, prepared as described for 1t. The reaction
mixture was kept under N2 at 40 C for 50 hr with magnetic stirring. Addition
of 2 N NH4OH and extraction with Et2O gave crude 4c, which was purified by
silica gel column chromatography (hexane–Et2O 19 : 1). Pure 4c (300 mg, 1.3
1
mmol, 43%) gave the following data: H NMR d 7.20 (1H, d, J 2.3 Hz, H-3),
6
(
1
.97 (1H, dd, J 2.3 and 8.3 Hz, H-5), 7.16 (1H, d, J 8.3 Hz, H-6), 7.02–7.18
3H, m, H-4 –H-6 ), 3.89 (3H, s, OMe), 2.33 (3H, s, H-8), 2.04 (3H, s, Me),
.92 (3H, s, Me). A pure sample of 4c (200 mg), dissolved in MeOH (10 ml),
′
′
was treated with NaBH4 excess at 40 C for 20 min. The reaction mixture was
added to 10% HCl and extracted with Et2O. Preparative TLC (benzene–Et2O,
1
4
7 : 3) gave pure 5c (180 mg): H NMR d 7.18 (1H, d, J 2.1 Hz, H-3), 6.97
(
1H, dd, J 2.1 and 8.4 Hz, H-5), 7.14 (1H, d, J 8.4 Hz, H-6), 7.00–7.23 (3H,
m H-4 –H-6 ), 4.60 and 4.72 (1H, q, J 6.2 Hz, H-7), 1.29 (3H, d, J 6.2 Hz,
′
′
H-8, 3.89 (3H, s, OMe), 2.01 and 1.96 (3H, s, Me), 2.36 (3H, s, Me).
To a solution of 5c (180 mg, 0.7 mmol) in dry xylene (1 ml), I2 (20 mg,
0
.08 mol) was added, and the mixture was kept at 140 C for 6 hr. Work-up as
1
for 6b gave 6c (143 mg, 0.6 mmol, 67%): H NMR d 6.90 (1H, dd, J 2.3 and
.3 Hz, H-5), 6.95–7.20 (5H, m), 6.41 (1H, dd, J 11.0 and 17.1 Hz, H-7), 5.64
1H, dd, J 1.8 and 17.1 Hz, H-8), 5.11 (1H, dd, J 1.8 and 11.0 Hz, H-8),
.90 (3H, s, OMe), 2.35 (3H, s, Me), 1.98 (3H, s, Me). Photocyclization of 6c
73 mg, 0.3 mmol) in an Ar atmosphere for 1 hr gave 2-methoxy-5,6-dimethyl-
8
(
3
(
1
9
,10-dihydrophenanthrene (1m) (55 mg, 0.2 mmol, 67%): H NMR d 6.86 (1H,
d, J 2.1 Hz, H-1), 6.84 (1H, dd, J 2.1 and 8.5 Hz, H-3), 7.55 (1H, d, J 8.5
Hz, H-4), 7.03 (2H, brs, H-7 and H-8), 2.73 (4H, brs, H-9 and H-10), 3.87 (3H,
s, OMe) 2.50 (3H, s, Me), 2.35 (3H, s, Me); 13C NMR d 111.2 (C-1), 159.0
(
(
(
C-2), 113.4 (C-3), 130.4 (C-4), 135.1 (C-5), 136.7 (C-6), 128.1 (C-7), 125.0
C-8), 31.0 (C-9), 31.0 (C-10), 137.8 (C-1a), 128.2 (C-4a), 141.8 (C-5a), 132.8
C-8a), 55.6 (OMe), 21.4 (Me), 19.4 (Me). BBr3 demethylation of 1m (45 mg,
1
0
.17 mmol) gave 1n (30 mg, 0.12 mmol, 66%): H NMR d 6.78 (1H, d, J 2.4
Hz, H-1), 6.75 (1H, dd, J 2.4 and 8.3 Hz, H-3), 7.48 (1H, d, J 8.3 Hz, H-4),
7
2
4
1
.03 (2H, brs, H-7 and H-8), 2.71 (4H, brs, H-9 and H-10), 2.49 (3H, s, Me),
.35 (3H, s, Me); 13C NMR d 112.3 (C-1), 154.1 (C-2), 114.4 (C-3), 130.2 (C-
), 135.0 (C-5), 136.3 (C-6), 127.7 (C-7), 124.7 (C-8), 30.4 (C-9), 30.6 (C-10),
36.8 (C-1a), 127.9 (C-4a), 142.3 (C-5a), 132.6 (C-8a), 21.0 (Me), 19.0 (Me).
Photocyclization of 6c (70 mg, 0.3 mmol) in the presence of atmospheric
1
oxygen gave 2m (50 mg, 0.18 mmol, 65%): H NMR d 7.28 (1H, d, J 2.3 Hz,
H-1), 7.21 (1H, dd, J 2.3 and 9.2 Hz, H-3), 8.68 (1H, d, J 9.2 Hz, H-4), 7.64
(
1H, d, J 8.7 Hz, H-7), 7.65 (1H, d, J 8.7 Hz, H-8), 7.57 (1H, d, J 7.9 Hz,

MIMICS OF Juncus COMPOUNDS
263
H-9), 7.38 (1H, d, J 7.9 Hz, H-10), 3.98 (3H, s, OMe), 2.94 (3H, s, Me), 2.57
1
3
(
3H, s, Me); C NMR d 114.8 (C-1), 157.4 (C-2), 108.8 (C-3), 129.8 (C-4),
1
1
2
0
2
7
35.4 (C-5), 136.4 (C-6), 128.2 (C-7), 125.8 (C-8), 128.0 (C-9), 126.3 (C-10),
32.6 (C-1a), 125.1 (C-4a), 129.7 (C-5a), 131.1 (C-8a), 55.4 (OMe), 22.0 (Me),
1.7 (Me). Demethylation of 2m (50 mg, 0.18 mmol) by BBr3 gave 2n (30 mg,
1
.12 mmol, 63%): H NMR d 7.27 (1H, d, J 2.3 Hz, H-1), 7.15 (1H, dd, J
.3 and 9.2, H-3), 8.65 (1H, d, J 9.2 Hz, H-4), 7.52 (1H, d, J 8.6 Hz, H-7),
.63 (1H, d, J 8.6 Hz, H-8), 7.63 (1H, d, J 7.9 Hz, H-9), 7.39 (1H, d, J 7.9
1
3
Hz, H-10), 2.92 (3H, s, Me), 2.55 (3H, s, Me); C NMR d 114.4 (C-1), 153.1
C-2), 111.7 (C-3), 130.0 (C-4), 135.3 (C-5), 136.5 (C-6), 128.3 (C-7), 126.1 (C-
), 127.9 (C-9), 125.2 (C-10), 132.4 (C-1a), 125.4 (C-4a), 129.8 (C-5a), 130.9
(
8
(
C-8a), 21.8 (Me), 21.6 (Me).
Synthesis of 2-Hydroxy-5,7-dimethyl-9,10-dihydrophenanthrene (1p) and 2-
Hydroxy-5,7-dimethylphenanthrene (2p). 2-Iodo-5-methoxyacetophenone (830
mg, 3 mmol) and iodo-2,3-dimethylbenzene (690 mg, 3 mmol) were cross cou-
pled as described for 1n. The reaction mixture was kept under N2 at 40 C for
4
5 hr under magnetic stirring. Work-up gave 4d, which was purified by column
chromatography (hexane–Et2O 9 : 1). Pure 4d (350 mg, 1.5 mmol, 50%) gave
1
the following data: H NMR d 7.00–7.11 (4H, m, H-3–H-6, H-5
′
), 7.19 (1H, d, J
2
.4 Hz, H-3 ), 7.16 (1H, dd, J 2.4 and 8.3 Hz, H-6 ), 3.89 (3H, s, OMe), 2.37
3H, s, H-8), 2.11 (3H, s, Me), 1.94 (3H, s, Me). NaBH4 excess reduction of 4d
′
′
(
(
4
300 mg, 1.3 mmol) gave crude 5d, purified by preparative TLC (benzene–Et2O
: 1). 5d (270 mg, 1.1 mmol, 90%) had: H NMR d 7.20 (1H, d, J 2.7 Hz,
1
H-3), 6.85 (1H, dd, J 2.7 and 8.4 Hz, H-5), 6.96–7.12 (4H, m, H-6, H-4
H-6 ), 4.61 and 4.75 (1H, q, J 6.5 Hz, H-7), 1.30 and 1.32 (3H, d, J 6.5 Hz,
H-8), 3.89 (3H, s, OMe), 2.06 and 2.02 (3H, s, Me), 2.38 (3H, s, Me).
′
–
′
To a solution of 5d (270 mg, 1.1 mmol) in dry xylene (1 ml), I2 (30 mg,
0
.14 mmol) was added and the mixture was kept at 140 C for 5 hr. Work-up
as for 6b gave 6d, purified by preparative TLC (hexane), (217 mg, 0.9 mmol,
1
8
1%): H NMR d 7.19 (1H, d, J 2.3 Hz, H-3), 6.88 (1H, dd, J 2.3 and 8.6,
H-5), 7.00–7.10 (4H, m, H-6, H-3 –H-6 ), 6.42 (1H, dd, J 11.0 and 17.1 Hz,
′
′
H-7), 5.65 (1H, dd, J 1.8 and 17.1 Hz, H-8), 5.10 (1H, dd, J 1.8 and 11.0
Hz, H-8), 3.89 (3H, s, OMe), 2.38 (3H, s, Me), 2.03 (3H, s, Me).
Photocyclization of 6d (100 mg, 0.4 mmol) in an Ar atmosphere for 1 hr
gave 2-methoxy-5,6-dimethyl-9,10-dihydrophenanthrene (1o) (75 mg, 0.3 mmol,
1
7
5%): H NMR d 6.87 (1H, d, J 2.1 Hz, H-1), 6.83 (1H, dd, J 2.1 and 8.5
Hz, H-3), 7.61 (1H, d, J 8.5 Hz, H-4), 7.02 (1H, brs, H-6), 6.95 (1H, brs, H-8),
.74 (4H, brs, H-9 and H-10), 3.87 (3H, s, OMe) 2.59 (3H, s, Me), 2.34 (3H,
2
1
3
s, Me); C NMR d 110.8 (C-1), 158.2 (C-2), 113.2 (C-3), 131.2 (C-4), 134.0
C-5), 129.0 (C-6), 136.0 (C-7), 126.3 (C-8), 30.5 (C-9), 30.7 (C-10), 138.8 (C-
a), 127.9 (C-4a), 141.3 (C-5a), 131.4 (C-8a), 55.2 (OMe), 22.9 (Me), 20.9 (Me).
BBr3 demethylation of 1o (45 mg, 0.17 mmol) gave 1p (30 mg, 0.12 mmol,
(
1

2
64
DELLAGRECA ET AL.
1
6
6%): H NMR d 6.77 (1H, d, J 2.4 Hz, H-1), 6.74 (1H, dd, J 2.4 and 8.3
Hz, H-3), 7.52 (1H, d, J 8.3 Hz, H-4), 6.99 (1H, brs, H-6), 6.93 (1H, brs, H-8),
.71 (4H, brs, H-9 and H-10), 2.57 (3H, s, Me), 2.33 (3H, s, Me); 13C NMR
d 1124 (C-1), 153.8 (C-2), 114.4 (C-3), 131.1 (C-4), 133.7 (C-5), 129.2 (C-6),
2
1
1
35.6 (C-7), 126.3 (C-8), 30.3 (C-9), 30.6 (C-10), 139.0 (C-1a), 127.9 (C-4a),
41.8 (C-5a), 131.1 (C-8a), 22.9 (Me), 20.9 (Me).
Photocyclization of 6c (100 mg, 0.4 mmol) in the presence of atmospheric
1
oxygen gave 2o (73 mg, 0.3 mmol, 75%): H NMR d 7.22–7.38 (3H, m, H-1,
H-3 and H-10), 8.89 (1H, d, J 9.0 Hz, H-4), 7.67 (2H, s, H-6 and H-8), 7.64
(
1H, d, J 8.4 Hz, H-9), 4.00 (3H, s, OMe), 3.13 (3H, s, Me), 2.55 (3H, s, Me);
1
3
C NMR d 115.5 (C-1), 157.1 (C-2), 109.3 (C-3), 134.6 (C-4), 134.9 (C-5),
28.5 (C-6), 134.6 (C-7), 127.3 (C-8), 128.2 (C-9), 126.8 (C-10), 133.0 (C-1a),
26.2 (C-4a), 128.1 (C-5a), 131.4 (C-8a), 55.4 (OMe), 27.3 (Me), 21.1 (Me).
1
1
Demethylation of 2o (36 mg, 0.2 mmol) by BBr3 gave 2p (27 mg, 0.14 mmol,
1
7
0%): H NMR d 7.26 (1H, d, J 1.9 Hz, H-1), 7.21 (1H, dd, J 1.9 and 9.2,
H-3), 8.81 (1H, d, J 9.2 Hz, H-4), 7.68 (2H, s, H-6 and H-8), 7.58 (1H, d,
8.4 Hz, H-9), 7.30 (1H, d, J 8.4 Hz, H-10), 3.01 (3H, s, Me), 2.51 (3H,
J
1
3
s, Me); C NMR d 115.2 (C-1), 152.9 (C-2), 112.1 (C-3), 132.9 (C-4), 134.9
(
(
C-5), 128.6 (C-6), 134.5 (C-7), 127.2 (C-8), 128.1 (C-9), 126.0 (C-10), 133.1
C-1a), 126.2 (C-4a), 127.5 (C-5a), 130.2 (C-8a), 27.2 (Me), 20.9 (Me).
Synthesis of 2-Hydroxy-5,8-dimethyl-9,10-dihydrophenanthrene (1r) and 2-
Hydroxy-5,8-dimethyl-phenanthrene (2r). Equimolar amounts of methyl 3-iodo-
-methylbenzoate (830 mg, 3 mmol), obtained from 3-iodo-4-methylbenzoic
4
acid by CH2N2 treatment in MeOH, and 3 (830 mg, 3 mmol) were added to the
flask containing the active Ni complex. After 35 hr at 40 C in N2 atmosphere,
the reaction mixture was worked up as previously described and chromatography
on a silica gel column (hexane–Et2O, 7 : 3) gave diastereoisomeric biphenyls 5e
1
(
245 mg, 1 mmol 34%): H NMR d 7.31 (1H, d, J 2.3 Hz, H-3), 6.91 (1H,
dd, J 2.3 and 8.4 Hz, H-5), 7.08 (1H, d, J 8.4 Hz, H-6), 7.31 (1H, d, J
.4 Hz, H-3 ), 7.92 (1H, dd, J 2.1 and 8.4 Hz, H-4 ), 7.85 (1H, d, J 2.1 Hz,
H-6 ), 4.51 and 4.69 (1H, q, J 6.5 Hz, H-7), 1.26 and 1.28 (3H, d, J 6.5 Hz,
8
′
′
′
H-8), 3.87 (6H, s, OMe), 2.10 and 2.14 (3H, s, Me). Dehydration of 5e (245
mg, 1 mmol) as reported gave 6e, purified by silica gel column chromatography
1
(
hexane–Et2O, 4 : 1) (205 mg, 0.8 mmol, 80%): H NMR d 7.20 (1H, d, J 2.3
Hz, H-3), 6.89 (1H, dd, J 2.3 and 8.4 Hz, H-5), 7.07 (1H, d, J 8.4 Hz, H-6),
.31 (1H, d, J 8.4 Hz, H-3 ), 7.99 (1H, dd, J 2.1 and 8.4 Hz, H-4 ), 7.81
1H, d, J 2.1 Hz, H-6 ), 6.32 (1H, dd, J 11.0 and 17.1 Hz, H-7), 5.68 (1H,
dd, J 1.8 and 17.1 Hz, H-8), 5.13 (1H, dd, J 1.8 and 11.0 Hz, H-8), 3.89
7
(
′
′
′
(
6H, s, OMe), 2.11 (3H, s, Me).
A pure sample of 6e (200 mg, 0.8 mmol) in dry benzene (6.5 ml) in a
Pyrex flask was irradiated under air atmosphere with a 450-W Hanovia lamp at
room temperature for 5 hr with magnetic stirring to give 2y (150 mg, 0.6 mmol,

MIMICS OF Juncus COMPOUNDS
265
1
7
7
8
5%): H NMR d 7.20–7.34 (2H, m, H-1 and H-3), 8.67 (1H, d, J 8.7, H-4),
.51 (1H, d, J 8.5 Hz, H-6), 7.99 (1H, d, J 8.5 Hz, H-7), 8.78 (1H, d, J
.0 Hz, H-9), 7.77 (1H, d, J 8.0 Hz, H-10), 4.00 (6H, s, OMe), 3.16 (3H, s,
Me). A sample of 2y (115 mg, 0.6 mmol) dissolved in dry toluene (3 ml) was
treated with Red-Al solution (3 mmol) for 2 hr. NaOH (2 N) was added and
the crude product was extracted with Et2O and chromatographed on silica gel
1
(
(
hexane–Et2O 9 : 1) to give 2q (90 mg, 0.45 mmol, 75%): H NMR d 7.22–7.38
3H, m, H-1, H-3 and H-7), 8.87 (1H, d, J 9.0 Hz, H-4), 7.40 (1H, d, J
8
4
1
1
5
.8 Hz, H-6), 8.00 (1H, d, J 7.6 Hz, H-9), 7.58 (1H, d, J 7.6 Hz, H-10),
.00 (3H, s, OMe), 3.11 (3H, s, Me), 2.75 (3H, s, Me); 13C NMR d 115.3 (C-1),
57.2 (C-2), 108.7 (C-3), 130.7 (C-4), 134.8 (C-5), 129.2 (C-6), 127.2 (C-7),
34.3 (C-8), 124.0 (C-9), 126.4 (C-10), 132.7 (C-1a), 125.8 (C-4a), 128.5 (C-
a), 132.9 (C-8a), 55.3 (OMe), 274 (Me), 20.3 (Me). Demethylation of 2q (40
1
mg, 0.2 mmol) by BBr3 gave 2r (35 mg, 0.18 mmol, 90%): H NMR d 7.28
(
9
1H, d, J 1.9 Hz, H-1), 7.18 (1H, dd, J 1.9 and 9.2, H-3), 8.81 (1H, d, J
.2 Hz, H-4), 7.65 (1H, d, J 8.5 Hz, H-6), 7.30 (1H, d, J 8.5 Hz, H-7), 7.95
1H, d, J 7.7 Hz, H-9), 7.35 (1H, d, J 7.7 Hz, H-10), 3.09 (3H, s, Me), 2.73
(
(
1
3
3H, s, Me); C NMR d 115.1 (C-1), 153.1 (C-2), 111.7 (C-3), 130.8 (C-4),
1
1
34.8 (C-5), 129.6 (C-6), 126.5 (C-7), 134.8 (C-8), 124.3 (C-9), 126.0 (C-10),
32.5 (C-1a), 126.2 (C-4a), 128.1 (C-5a), 132.9 (C-8a), 27.4 (Me), 20.3 (Me).
A sample of 2q (40 mg, 0.2 mmol) was photoreduced as reported for 2s to
1
give 1q (30 mg, 0.15 mmol, 75%): H NMR d 6.85 (1H, d, J 2.1 Hz, H-1),
6
.83 (1H, dd, J 2.1 and 8.5 Hz, H-3), 7.58 (1H, d, J 8.5 Hz, H-4), 7.11 (1H,
d, J 8.1 Hz, H-6), 7.01 (1H, d, J 8.1 Hz, H-7), 2.72 (4H, brs, H-9 and H-10),
3
1
1
1
.87 (3H, s, OMe) 2.58 (3H, s, Me), 2.33 (3H, s, Me); 13C NMR d 110.7 (C-1),
58.1 (C-2), 112.7 (C-3), 129.5 (C-4), 134.3 (C-5), 129.5 (C-6), 127.9 (C-7),
31.3 (C-8), 26.0 (C-9), 30.0 (C-10), 137.4 (C-1a), 127.9 (C-4a), 141.4 (C-5a),
32.1 (C-8a), 55.2 (OMe), 22.9 (Me), 19.9 (Me). BBr3 demethylation of 1q (20
1
mg, 0.1 mmol) gave 1r (15 mg, 0.09 mmol, 90%): H NMR d 6.76 (1H, d, J
2
.4 Hz, H-1), 6.74 (1H, dd, J 2.4 and 8.3 Hz, H-3), 7.51 (1H, d, J 8.3
Hz, H-4), 7.10 (1H, d, J 8.1 Hz, H-6), 7.00 (1H, d, J 8.1 Hz, H-7), 2.71
(
(
(
(
4H, brs, H-9 and H-10), 2.57 (3H, s, Me), 2.34 (3H, s, Me); 13C NMR d 112.3
C-1), 153.7 (C-2), 114.2 (C-3), 129.4 (C-4), 134.1 (C-5), 129.3 (C-6), 128.2
C-7), 131.6 (C-8), 26.2 (C-9), 30.2 (C-10), 137.6 (C-1a), 127.9 (C-4a), 141.8
C-5a), 132.2 (C-8a), 22.8 (Me), 20.1 (Me).
Bioassay. The strain UTEX 1648 Selenastrum capricornutum was main-
tained on Bold basal medium (BBM) solidified with agar 1.5% in continuous
light at 23 C. Fresh axenic cultures for the experiments were grown in 100-ml
cylinders on the same culture medium. For growth tests, the compounds were
dissolved in acetone. Each soluion (20 ml) was added to test tubes containing
4
5
6
1
ml of inoculated medium, giving final concentrations of 10 , 5 × 10 , and
5
0
M. Controls containing only acetone also were tested. The test tubes were

2
66
DELLAGRECA ET AL.
incubated at 23 C on a shaking apparatus previously described (Aliotta et al.,
2
1
991). Total irradiation of 150 mE sec m was provided by daylight fluorescent
/
/
lamps (Philips TLD 30 w 55) from below the apparatus. The photoperiod was
6 hr light and 8 hr dark. Growth of cultures was followed daily, either by mea-
/
1
suring the absorbance increase at 550 nm with a Bausch & Lomb Spectronic 20
colorimeter or by counting the cell numbers with a Thoma blood-counting cham-
6
6
ber. The cell numbers of the initial inocula ranged from 10 to 1.5 × 10 ml,
/
corresponding to 0.05–0.06 units of absorbance. Growth experiments were car-
ried out in triplicate. To test statistical significance of results, one-way ANOVA
was performed with P 0.05. For each compound, a comparison among means
was performed by Student-Newman-Keuls test (SNK), with P 0.05. The sta-
tistical package SPSS was used.
The index of inhibition for compounds was calculated as [1 (Xa Ya)] ×
/
1
00 (Blankley, 1973), where Xa is the growth rate of the alga in the presence of
the compound tested and Ya is the growth rate of the control.
RESULTS AND DISCUSSION
The basic formulas and substitutions of groups for the compounds synthe-
sized are shown in Figure 1. 1-(2-Iodo-5-methoxy)-phenylethanol (3), synthe-
sized as reported in the previous paper (DellaGreca et al., 1999), was used as
a starting block in the synthesis of 6,7-, 6,8-, and 7,8-dimethyl compounds. In
all the reactions, equimolar amounts of 3 and iodoxylene were added at once
to the reaction mixture containing the active nickel complex generated in situ
by action of dust zinc on NiCl2(PPh3)2 (Tiecco et al., 1984). Coupling of 3
with iodo-3,4-dimetilbenzene gave biphenyl 5b, which was converted into 6b by
dehydration with I2 in dry xylene at 140 C. All attempts to obtain 2-methoxy-
6
,7-dimethyl-9,10-dihydrophenanthrene (1s) and 2-methoxy-7,8-dimethyl-9,10-
dihydrophenanthrene (1w) by UV irradiation of 6b in an Ar atmosphere (Padwa
et al., 1977) failed, while photocyclization of 6b by UV irradiation in an
air atmosphere easily gave a mixture of 2-methoxy-6,7-dimethylphenanthrene
(
2s) and 2-methoxy-7,8-dimethylphenanthrene (2w), which were separated by
HPLC-NH2. Demethylation by BBr3 in CH2Cl2 for 3 hr at 70 C converted
s and 2w into 2-hydroxy-6,7-dimethylphenanthrene (2t) and 2-hydroxy-7,8-
dimethylphenanthrene (2x).
-Methoxy-6,7-dimethyl-9,10-dihydrophenanthrene (1s) and 2-methoxy-
,8-dimethyl-9,10-dihydrophenanthrene (1w) were obtained from 2s and 2w by
2
2
7
photoreduction with NaBH4 in EtOH and Et3N and UV irradiation (Nien-chu
et al., 1984). Subsequent demethylation as above reported gave 2-hydroxy-
6
,7-dimethyl-9,10-dihydrophenanthrene (1t) and 2-hydroxy-7,8-dimethyl-9,10-
dihydrophenanthrene (1x).

MIMICS OF Juncus COMPOUNDS
267
FIG. 1. The basic structural skeletons of compounds synthesized, and the various groups
that were substituted at the positions marked by R1, R2, R3, and R4.
Coupling of 3 with iodo-3,5-dimethylbenzene gave 5a, which, through the
styrene derivative 5b was converted by UV irradiation into 2-methoxy-6,8-
dimethyl-9,10-dihydrophenanthrene (1u) in an argon atmosphere and into 2-
methoxy-6,8-dimethylphenanthrene (2u) in the presence of atmospheric oxy-
gen. Demethylation of 1u and 2u afforded 2-hydroxy-6,8-dimethyl-9,10-
dihydrophenanthrene (1v) and 2-hydroxy-6,8-dimethylphenanthrene (2v).
The synthesis of dimethyl compounds with a methyl at C-5 by cross-
coupling of 3 with the right iodoxylene failed as the steric hindrance of

2
68
DELLAGRECA ET AL.
the methyl caused long reaction times, and in such conditions the primary
process was replacement of iodine by alcoholic hydrogen. The same prob-
lem was overcome in the synthesis of 2-hydroxy-5-methyl-9,10-dihydrophenan-
threne (1d) and 2-hydroxy-5-methylphenanthrene (2d) by cross-coupling ortho
iodotoluene with 2-iodo-5-methoxyacetophenone. In the same way, the synthe-
sis of 2-hydroxy-5,6-dimethyl-9,10-dihydrophenanthrene (1n), 2-hydroxy-5,7-
dimethyl-9,10-dihydrophenanthrene (1p), 2-hydroxy-5,6-dimethylphenanthrene
(
2n), and 2-hydroxy-5,7-dimethylphenanthrene (2p) was performed. Couplings
of 2-iodo-5-methoxyacetophenone with iodo-2,3-dimethylbenzene and iodo-
,4-dimethylbenzene gave ketones 4c and 4d, respectively. NaBH4 reduction
2
afforded carbinols 5c and 5d. These compounds, obtained as diastereoisomeric
mixtures because free rotation of the rings about each other is hindered for
the presence of the methyl at C-2 , were dehydrated directly to 6c and 6d.
′
Photocyclization of 6c in the absence and in the presence of atmospheric
oxygen gave 2-methoxy-5,6-dimethyl-9,10-dihydrophenanthrene (1m) and 2-
methoxy-5,6-dimethylphenanthrene (2m), respectively, which were converted
into 1n and 2n by BBr3 demethylation. Irradiation in both the conditions of 6d
gave 2-methoxy-5,7-dimethyl-9,10-dihydrophenanthrene (1o) and 2-methoxy-
5
,7-dimethylphenanthrene (2o), which were demethylated to 1p and 2p. All
attempts to synthesize 2-hydroxy-5,8-dimethyl-9,10-dihydrophenanthrene (1r)
and 2-hydroxy-5,8-dimethylphenanthrene (2r) this way failed because of very
long reaction times in which no coupling between 2-iodo-5-methoxyacetophe-
none and iodo-2,5-dimethylbenzene was obtained.
Semmelhack (1981) observed an efficient coupling of aryl halides bearing
aldehyde, ketone, ester, and nitrile groups. On this basis, 3 was cross-coupled
with methyl 3-iodo-4-methylbenzoate to give the corresponding diastereoiso-
meric biaryls 5e that were dehydrated to 6e. Photocyclization of 6e in both
the reported conditions gave 9,10-dihydrophenanthrene (1y) and phenanthrene
(2y), which were converted into 2-methoxy-5,8-dimethyl-9,10-dihydrophenan-
threne (1q) and 2-methoxy-5,8-dimethylphenanthrene (2q) by sodium bis(2-
methoxyethoxy)aluminum hydride. Final demethylation of 1q and 2q gave 1r
and 2r.
The 9,10-dihydrophenanthrenes and phenanthrenes purified by HPLC were
5
4
assayed on Selenastrum capricornutum at concentrations of 10 –10 M. The
compounds were stable in the assay conditions and the results had statistical
significance (Tables 1 and 2). All dimethyl-9,10-dihydrophenanthrenes cause
full inhibition of algal growth at 10 4 M concentration and no differences were
observed between the hydroxy and the methoxy derivatives. High activity is
maintained at 5 × 10 5 M, while at 10 5 M only 2-methoxy-5,6-dimethyl-9,10-
dihydrophenanthrene (1m), 2-methoxy-5,7-dimethyl-9,10-dihydrophenanthrene
(1o), 2-methoxy-6,8-dimethyl-9,10-dihydrophenanthrene (1u), and 2-methoxy-
7
,8-dimethyl-9,10-dihydrophenan-threne (1w) are still active. These compounds

TABLE 1. INHIBITION (%) OF GROWTH OF S. capricornutum BY SYNTHETIC 9,10-DIHYDROPHENANTHRENESa
1
m
1n
1o
1p
1q
1r
1s
1t
1u
1v
1w
1x
1
5
1
0 4
× 10
M
100 d
60 c
40 b
0 a
100 b
100 b
0 a
100 b
100 b
100 b
0 a
98 b
98 b
0 a
100 b
100 b
0 a
100 b
100 b
0 a
100 b
100 b
0 a
100 b
100 b
0 a
100 d
89 c
60 b
0 a
100 c
71 b
0 a
100 b
100 b
100 b
0 a
100 b
100 b
0 a
5
M
5
0
M
Control
0 a
0 a
0 a
0 a
0 a
0 a
0 a
0 a
a
In each column values followed by different letters are statistically significant. Student-Newman-Keuls test; P 0.05.

TABLE 2. INHIBITION (%) OF GROWTH OF S. capricornutum BY SYNTHETIC PHENANTHRENES
2
m
2n
2o
2p
2q
2r
2s
2t
2u
2v
2w
2x
1
5
1
0 4
× 10
M
100 b
100 b
0 a
98 b
98 b
98 b
0 a
0 a
0 a
0 a
0 a
100 c
100 c
50 b
0 a
98 b
98 b
0 a
100 b
100 b
0 a
70 c
70 c
22 b
0 a
100 c
95 b
95 b
0 a
100 b
100 b
0 a
70 c
50 b
50 b
0 a
75 c
75 c
20 b
0 a
100 c
95 b
95 b
0 a
5
M
5
0
M
Control
0 a
0 a
0 a
0 a
a
In each column values followed by different letters are statistically significant. Student-Newman-Keuls test; P 0.05.

MIMICS OF Juncus COMPOUNDS
271
have a methyl at C-5 or at C-8, and when the other methyl is at C-7, 100%
activity is observed. Except for 2-methoxy-5,7-dimethylphenanthrene (2o), all
the dimethylphenanthrenes have high activity at 10 4 and 5 × 10 5 M concen-
trations with no differences among hydroxy and methoxy derivatives. At the low-
est concentration, only 2-hydroxy-5,6-dimethylphenanthrene (2n), 2-hydroxy-
5
,7-dimethylphenanthrene (2p), 2-hydroxy-6,7-dimethylphenanthrene (2t), 2-
hydroxy-6,8-dimethylphenanthrene (2v), and 2-hydroxy-7,8-dimethyl-phenan-
threne (2x) are active, and 2n, 2t, and 2x still cause full inhibition.
In conclusion, all the synthetic phenanthrenes and 9,10-dihydrophenan-
threnes cause inhibition of algal growth in the examined concentration range. A
comparison among monomethyl and dimethyl compounds shows that at the high-
est concentration the monomethyl derivatives are less active than the dimethyl
derivatives, while at the lowest concentration the activity goes in the opposite
direction.
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