Discovery of diphenylmethane analogs as anti-bovine diarrhea viral agents

Article abstract of DOI:10.1016/j.bmcl.2009.04.137

Based on antiviral screening of our diphenylmethane derivatives prepared as steroid substitutes, we identified a 1,1-diphenylcyclobutane analog (9) and two diethyldiphenylsilane analogs (12 and 13) as superior lead compounds with potent anti-bovine viral

Full text of DOI:10.1016/j.bmcl.2009.04.137

Bioorganic & Medicinal Chemistry Letters 19 (2009) 3157–3161
Contents lists available at ScienceDirect
Bioorganic & Medicinal Chemistry Letters
journal homepage: www.elsevier.com/locate/bmcl
Discovery of diphenylmethane analogs as anti-bovine diarrhea viral agents
Shinnosuke Hosoda a, , Hiroshi Aoyama a, , Yukinori Goto b, Mohammed T. A. Salim b, Mika Okamoto b,
a,
Mariko Hashimoto a, Masanori Baba b, , Yuichi Hashimoto
*
*
a Institute of Molecular & Cellular Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan
b Division of Antiviral Chemotherapy, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka,
Kagoshima 890-8544, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Based on antiviral screening of our diphenylmethane derivatives prepared as steroid substitutes, we
identified a 1,1-diphenylcyclobutane analog (9) and two diethyldiphenylsilane analogs (12 and 13) as
superior lead compounds with potent anti-bovine viral diarrhea virus (BVDV) activity, having 50% effec-
tive concentration (EC50: based on reduction of BVDV replication-induced cell destruction) and 50% cyto-
Received 8 April 2009
Revised 28 April 2009
Accepted 29 April 2009
Available online 3 May 2009
toxic concentration (CC50: based on reduction of viable cell number) values of 6.2–8.4
respectively, in Madin–Darby bovine kidney (MDBK) cells infected with BVDV.
lM and >100 lM,
Keywords:
Antiviral agents
Ó 2009 Elsevier Ltd. All rights reserved.
Bovine viral diarrhea virus
Diphenylmethane
HCV infection is thought to be a major cause of human hepatitis
globally.1,2 Currently, the standard treatment for chronic hepatitis
copossess
a
-glucosidase-inhibitory activity.13,15 This led us
hypothesize a relationship between structures exhibiting a-gluco-
C consists of pegylated interferon (IFN)-
a
in combination with the
sidase-inhibitory activity and the steroid skeleton; we have also
proposed a multi-template hypothesis for molecular design of bio-
logically active compounds.15,16 The multi-template hypothesis is
based on the fact that there exist only a limited number of protein
domain folding structures in spite of the existence of a huge num-
ber of protein amino acid sequences.16–18 This hypothesis has led
us to design and synthesize various nuclear receptor ligands and
steroid-related enzyme inhibitors with a 3,3-diphenylpentane
skeleton.16,19–22 These considerations suggested that 3,3-diphenyl-
pentane and/or related skeleton(s) might be superior multi-tem-
plates that can substitute for a steroid skeleton.
In this context, we decided to examine the anti-BVDV activity of
our 3,3-diphenylpentane derivatives prepared as nuclear receptor
ligands. Anti-BVDV activity of the compounds was evaluated in
Madin–Darby bovine kidney (MDBK) cells infected with BVDV
(Nose strain), as described previously.6,23 Here, we report the dis-
covery of anti-BVDV activity of 3,3-diphenylpentane derivatives,
as well as structural development studies to increase the activity.
The anti-BVDV activity and cytotoxicity of the test compounds
are presented as EC50 and CC50 values, where EC50 is the 50% effec-
tive concentration based on the reduction of BVDV replication-in-
duced cell destruction, and CC50 is the 50% cytotoxic concentration
based on the reduction of viable cell number. The selectivity index
nucleoside analog ribavirin (1-b- -ribofuranosyl-1,2,4-triazole-3-
D
carboxamide). However, the virus cannot be eliminated from
approximately half of infected patients treated with this combina-
tion.3 Therefore, alternative agents for the treatment and preven-
tion of HCV infection are urgently needed. HCV belongs to the
Flaviviridae family, as does bovine viral diarrhea virus (BVDV),1
and because HCV does not replicate efficiently in cell cultures or
animals, BVDV is thought to be a good model for human HCV.4–6
We have been engaged in structural development studies of
anti-BVDV agents based on a
rived from thalidomide.7,8 These previous studies were inspired by
our successful development of -glucosidase inhibitors derived
from thalidomide, because -glucosidase inhibitors may elicit anti-
c-carboline skeleton, which was de-
a
a
viral activity through inhibition of normal trimming of viral enve-
lope glycoprotein which is necessary for viral maturation/
proliferation.9–11
On the other hand, we recently reported that some of our a-glu-
cosidase inhibitors derived from thalidomide also act as ligands for
liver X receptor (LXR), a member of the nuclear receptor superfam-
ily, whose physiological ligands are oxysterols, including 24(S),25-
epoxycholesterol (EC) and 22-(R)-hydroxycholesterol (HC).12–15
We also found that several typical synthetic/natural LXR ligands
(SI) is determined as CC50/EC50
.
First we screened anti-BVDV activity of our 3,3-diphenylpen-
tane derivatives prepared as nuclear receptor ligands.19–21 Among
these compounds, we found that our potent androgen receptor
* Corresponding authors.
E-mail addresses: m-baba@m2.kufm.kagoshima-u.ac.jp (M. Baba), hashimot@
iam.u-tokyo.ac.jp (Y. Hashimoto).
The first two authors contributed equally.
(AR)/vitamin D
receptor (VDR) dual ligand, DPP-0111 (1),20
0960-894X/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.bmcl.2009.04.137

3158
S. Hosoda et al. / Bioorg. Med. Chem. Lett. 19 (2009) 3157–3161
possesses moderate but promising anti-BVDV activity with EC50
CC50 values of 8.9/82 M (Fig. 1). Its VDR-selective analog, DPP-
1023 (2),20 was also active (EC50/CC50 = 25/43
M), but its anti-
BVDV and cytotoxic activities were weaker and stronger than those
of 1, respectively, resulting in a decrease of SI value from 9.21 to
1.72. This result suggests that a hydroxyl group(s) and/or a hydro-
gen donor(s) on the side chain(s) enhances the cytotoxic activity.
Therefore, we prepared the N-benzyl analog of 1, which does not
possess a hydrogen donor (3: Fig. 1).24 As expected, the cytotoxic
activity of 1 disappeared upon N-benzylation (EC50/CC50 = 28/
/
the methods described previously.19–22,29–31 As expected, com-
pounds 8–10 all showed no apparent cytotoxicity (CC50 values of
l
l
the compounds were all >100
BVDV activity (EC50 values of the compounds were 6.3–13.2
l
M) without any decrease of anti-
M).
l
The anti-BVDV activity of compounds 8–10 decreased in the fol-
lowing order: 9 (cyclobutyl) > 8 (dimethyl) ꢀ /ꢁ10 (cyclopentyl).
This higher activity of 9 compared with 8 and 10 seems to be
attributable to the strained geometry around the quaternary
methine carbon atom. Preliminary calculation based on the MMFF
94 force field indicated that the dihedral angle between the two
phenyl rings of 9 (106.9°) is smaller than those of compounds 8
and 10 (109–111°) (Fig. 4). Nevertheless, the distance between
the two phenyl carbons bound to the methine carbon of 9
(2.61 Å) was calculated to be longer than those of compounds 8
and 10 (2.52–2.55 Å), because of the lengthened C–C bond be-
tween the methine carbon and the adjacent phenyl carbon of com-
pound 9, at least as determined with the MMFF 94 force field
calculation method (Fig. 4). Of course, the calculated angles/dis-
tances may not be correct, and in fact, other calculation methods,
including those based on B3LYP/3-21G, B3LYP/6-31G and MP2/6-
>100 lM), while the anti-BVDV activity of 3 remained (though it
was weaker than that of 1).
To confirm this hydrogen donor effect, several derivatives con-
taining a hydrogen donor(s) (compounds 4–7) were prepared
(Fig. 2), using methods described previously.19–22,25–28 Briefly, a
bisphenol-type core skeleton was prepared by condensation of
phenol or o-cresol with pentan-3-one or cyclohexanone. Treatment
of the obtained bisphenol derivatives with aniline or o-toluidine
gave core skeletons of 5 and 7. The phenolic hydroxyl and/or amino
group were acylated/alkylated by using usual organic synthetic
methods.
*
31+G , gave different values individually. However, regardless of
All of these compounds (4–7) bearing an aryl-XH (X = O or N)
group(s) showed moderate (unfavorable) cytotoxic activity with
CC50 values of 39–50 lM, as expected. Therefore, we chose the
bis-pivaloylmethyloxyphenylmethane skeleton for further struc-
tural development, and synthesized compounds 8–10 (Fig. 3) using
the correctness of the calculated values, these considerations led
us to design silyl analogs 11–14 (Fig. 5), in which the correspond-
ing dihedral angles and distances were calculated to be 103–104°
and 2.98–2.99 Å, respectively, by means of the same MMFF 94
force field-based calculation method (Fig. 4).
Figure 1. Anti-BVDV activity of DPP-0111 (1), DPP-1023 (2) and N-benzyl analog of DPP-0111 (3).
Figure 2. Anti-BVDV activity of diphenylpentane derivatives bearing a hydrogen donor group(s).

S. Hosoda et al. / Bioorg. Med. Chem. Lett. 19 (2009) 3157–3161
3159
Figure 3. Anti-BVDV activity of bis-pivaloyloxyphenylmethane derivatives.
Figure 4. Dihedral angle between the two phenyl rings and distance between the two phenyl carbons bound to the nethine carbon of compounds 8–4 calculated based on
MMFF 94 force field.
Compounds 11–14 were synthesized as shown in Scheme 1 by
applying the method described by Tagle et al.32 Briefly, 4-bromo-2-
methylphenol (prepared from o-cresol by treatment with NBS in
CH3CN) or p-bromophenol was reacted with dichlorodiethylsilane
or dichlorodimethylsilane in the presence of n-BuLi in THF. The
resulting bisphenylsilane derivative was further treated with 1-
chloropinacolone in the presence of NaH in DMF, giving com-
pounds 11–14.33–36 Compound 11 showed similar activity to that
Figure 5. Anti-BVDV activity of bis-pivaloyloxyphenylsilane derivatives.

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S. Hosoda et al. / Bioorg. Med. Chem. Lett. 19 (2009) 3157–3161
Scheme 1. R1/R2 = H or CH3. Reagents and conditions: (a) NBS, CH3CN, 75%; (b) n-BuLi, SiEt2Cl2 (or SiMe2Cl2), THF, 52%; (c) NAH, 1-chloropinacolone, DMF, 19%.
13. Dodo, K.; Aoyama, A.; Noguchi-Yachide, T.; Makishima, M.; Miyachi, H.;
of the corresponding carbon analog 8, and compounds 12 and 13
showed potent anti-BVDV activity, comparable to that of 9, with
no apparent cytotoxicity, as expected (Fig. 5). In the case of silyl
analogs, the existence of a hydroxyl group, that is, compound 14,
resulted in appearance of cytotoxicity, as was the case for the car-
bon analogs (Fig. 2). The anti-BVDV activity and the cytotoxicity
elicited by 14 are similar to those elicited by the corresponding
carbon analog 4. Although we could prepare potent anti-BVDV
agents (12 and 13) designed based on MMFF 94 force field-based
calculation, it was found to be difficult to discuss the observed
structure–activity relationships by the use of other calculation
methods, including B3LYP/3-21G, B3LYP/6-31G and MP2/6-
Hashimoto, Y. Bioorg. Med. Chem. 2008, 16, 4272.
14. Noguchi-Yachide, T.; Miyachi, H.; Apyama, A.; Makishima, M.; Aoyama, H.;
Hashimoto, Y. Chem. Pharm. Bull. 2007, 55, 1750.
15. Hashimoto, Y. Arch. Pharm. Life Sci. 2008, 341, 536.
16. Hosoda, S.; Matsuda, D.; Tomoda, H.; Hashimto, Y. Mini-Rev. Med. Chem. 2009,
9, 572.
17. Koonin, E. V.; Wolf, Y. I.; Karev, G. P. Nature 2002, 420, 218.
18. Grishin, N. V. J. Struct. Biol. 2001, 134, 167.
19. Kainuma, M.; Kasuga, J.; Hosoda, S.; Wakabayasgi, K.; Tanatani, A.; Nagasawa,
K.; Miyachi, H.; Makishima, M.; Hashimoto, Y. Bioorg. Med. Chem. 2006, 16,
3213.
20. Hosoda, S.; Tanatani, A.; Wakabayashi, K.; Makishima, M.; Imai, K.; Miyachi, H.;
Nagasawa, K.; Hashimoto, Y. Bioorg. Med. Chem. 2006, 14, 5489.
21. Hosoda, S.; Hashimoto, Y. Pure Appl. Chem. 2007, 79, 615.
22. Hosoda, S.; Hashimoto, Y. Bioorg. Med. Chem. Lett. 2007, 17, 4895.
23. Baba, C.; Yanagida, K.; Kanzaki, T.; Baba, M. Antiviral Chem. Chemother. 2005, 16,
33.
*
31+G . For example, calculation using B3LYP/3-21G gave a quite
small differences between the dihedral angles of Ph-C-Ph and Ph-
Si-Ph, that is, 110–111° and 109–110°, respectively. The distances
between the two phenyl carbons bound to the methine carbon of
dimethyl, diethyl, cyclobutyl and cyclopentyl derivatives were cal-
culated to be 2.52–2.54 Å (almost no difference), and those of silyl
analogs were calculated to be ca. 3.12 Å by the same B3LYP/3-21G
calculation method.
24. 1-(N-Benzyl-N-(4-(3-(4-(3,3-dimethyl-2-oxobutylhydroxy)-3-methylphenyl)pentan-
3-yl)-2-methylphenyl)amino)-3,3-dimethylbutan-2-one
(3):
Pale
yellow
amorphous. 1H NMR (500 MHz, CDCl3/d): 7.30–7.20 (m, 5H), 7.00 (d,
J = 8.6 Hz, 1H), 6.91–6.87 (m, 4H), 6.49 (d, J = 9.4 Hz, 1H), 4.83 (s, 2H), 4.30
(s, 2H), 3.88 (s, 2H), 2.31 (s, 3H), 2.23 (s, 3H), 2.00 (q, J = 7.3 Hz, 4H), 1.25 (s,
9H), 0.99 (s, 9H), 0.57 (t, J = 7.3 Hz, 6H). HRMS (FAB, m/z, [M+H]+) calcd for
C38H52NO3, 570.3947; found 570.3939.
25. 1-(4-(3-(4-Hydroxy-3-methylphenyl)pentan-3-yl)-2-methylphenoxy)-3,3-dimethyl-
butan-2-one (4): White crystals. Mp 95–97 °C. 1H NMR (500 MHz, CDCl3/d):
691–685 (m, 4H), 6.65 (d, J = 8.1 Hz, 1H), 6.49 (d, J = 8.1 Hz, 1H), 4.83 (s, 2H),
4.50 (s, 1H), 2.23 (s, 3H), 2.19 (s, 3H), 2.00 (q, J = 7.3 Hz, 4H), 1.25 (s, 9H), 0.59
(t, J = 7.3 Hz, 6H). HRMS (FAB, m/z, [M+H]+) calcd for C25H34O3, 382.2508; found
382.2508.
In conclusion, among the compounds presented in this Letter,
the cyclobutane analog (9) and silyl analogs (12 and 13) showed
superior activity with EC50/CC50 values of 6.3/>100, 8.4/>100
lM
and 6.2/>100 M, respectively. The SI values of these compounds
l
26. 4-(3-(4-Acetamido-3-methylphenyl)pentan-3-yl)-2-methylphenyl diethylcarbamate
(5): White foam. Mp 58–62 °C. 1H NMR (500 MHz, CDCl3/d) 7.66 (d, J = 9.0 Hz,
1H), 7.05 (d, J = 9.0 Hz, 1H), 6.98–6.93 (m, 4H), 6.86 (s, 1H), 3.45 (q, J = 6.8 Hz,
2H), 3.38 (q, J = 6.8 Hz, 2H), 2.19 (s, 3H), 2.19 (s, 3H), 2.15 (s, 3H), 2.04 (q,
J = 7.3 Hz, 4H), 1.26 (t, J = 6.8 Hz, 3H), 1.19 (t, J = 6.8 Hz, 3H), 0.59 (t, J = 7.3 Hz,
6H). HRMS (FAB, m/z, [M+H]+) calcd for C26H37N2O3, 425.2804; found
425.2787.
exceeded at least 11.9, suggesting that they represent superior lead
compounds for the development of novel antiviral agents. Mecha-
nistic studies, especially identification of the target molecule(s) of
compounds 9, 12 and 13, are under way.
27. 3,3-Bis(4-hydroxyphenyl)pentane (6): White crystals. Mp 201–203 °C. 1H NMR
(500 MHz, CDCl3/d): 7.02 (d, J = 8.6 Hz, 4H), 6.71 (d, J = 8.6 Hz, 4H), 4.63 (s, 1H),
2.02 (q, J = 7.3 Hz, 4H), 0.60 (t, J = 7.3 Hz, 6H). HRMS (FAB, m/z, [M+H]+) calcd
for C17H20O2, 256.1463; found 256.1467.
Acknowledgments
The authors are grateful to Dr. Shinya Usui, Mr. Taniyuki Furuy-
ama and Mr. Kenji Ohgane for helpful discussions and force field
calculations. The work described in this Letter was partially sup-
ported by the Science and Technology Incubation Program in Ad-
vanced Regions, Japan Science and Technology Agency.
28. 4-(1-(4-Aminophenyl)cyclohexyl)phenol (7): White crystals. Mp 142–143 °C. 1H
NMR (500 MHz, CDCl3/d): 7.10 (d, J = 8.6 Hz, 2H), 7.04 (d, J = 8.6 Hz, 2H), 6.70
(d, J = 8.6 Hz, 2H), 6.61 (d, J = 8.6 Hz, 2H), 4.77 (br s, 1H), 3.55 (br s, 2H), 2.18–
2.05 (m, 4H), 1.53–1.47 (m, 6H). HRMS (FAB, m/z, [M+H]+) calcd for C18H21NO3,
267.1623; found 267.1630.
29. 2,2-Bis[4-(3,3-dimethyl-2-oxobutoxy)-3-methylphenyl]propane
(8):
White
crystals. Mp 119–121 °C. 1H NMR (500 MHz, CDCl3/d): 6.99 (s, 2H), 6.93 (dd,
J = 8.6, 2.6 Hz, 2H), 6.49 (d, J = 8.6 Hz, 2H), 4.84 (s, 4H), 2.25 (s, 6H), 1.59 (s, 6H),
1.25 (s, 18H). 13C NMR (125 MHz, CDCl3/d): 210.0, 154.1, 143.5, 129.6, 126.4,
124.7, 110.4, 69.5, 43.2, 41.5, 31.0, 26.3, 16.6. HRMS (FAB, [M+H+]) calcd for
C29H41O4, 453.3005, found 453.3011.
References and notes
1. Liang, T. J.; Rehermann, B.; Seeff, L. B.; Hoofnagle, J. H. Ann. Int. Med. 2000, 132,
296.
2. Hayashi, P. H.; Di Bisceglie, A. M. Med. Clin. North Am. 2005, 89, 371.
3. McHutchison, J. G.; Gordon, S. C.; Schiff, E. R.; Shiffman, M. L.; Lee, W. M.;
Rustgi, V. K.; Goodman, Z. D.; Ling, M. H.; Cort, S.; Albrecht, J. K. N. Eng. J. Med.
1998, 339, 1485.
4. Buckwold, V. E.; Beer, B. E.; Donis, R. O. Antiviral Res. 2003, 60, 1.
5. Buckwold, V. E.; Wei, J.; Wenzel-Mathers, M.; Russell, J. Antimicrob. Agents
Chemother. 2003, 47, 2293.
30. 1,1-Bis[4-(3,3-dimethyl-2-oxobutoxy)-3-methylphenyl]cyclobutane (9): White
solid. Mp 73–75 °C. 1H NMR (500 MHz, CDCl3/d): 7.05 (s, 2H), 7.00 (dd,
J = 8.6, 2.7 Hz, 2H), 6.52 (d, J = 8.6 Hz, 2H), 4.81 (s, 4H), 2.64 (t, J = 7.7 Hz, 4H),
2.26 (s, 6H), 1.91 (quint, J = 7.7 Hz, 2H), 1.25 (s, 18H). 13C NMR (125 MHz,
CDCl3/d): 210.0, 154.1, 142.8, 128.9, 126.8, 124.1, 110.8, 69.6, 49.9, 43.2, 35.1,
26.3, 16.6, 16.5. HRMS (FAB, [M+]) calcd for C30H40O4, 464.2927, found
464.2931.
6. Yanagida, K.; Baba, C.; Baba, M. Antiviral Res. 2004, 64, 195.
7. Sako, K.; Aoyama, H.; Sato, S.; Hashimoto, Y.; Baba, M. Bioorg. Med. Chem. 2008,
16, 3780.
8. Aoyama, H.; Sako, K.; Sato, S.; Nakamura, M.; Miyachi, H.; Baba, M.; Hashimoto,
Y. Heterocycles 2009, 77, 779.
9. Sou, S.; Mayumi, S.; Takahashi, H.; Yamasaki, R.; Ladoya, S.; Sodeoka, M.;
Hashimoto, Y. Bioorg. Med. Chem. 2000, 10, 1081.
10. Takahashi, H.; Sou, S.; Yamasaki, R.; Sodeoka, M.; Hashimoto, Y. Chem. Pharm.
Bull. 2000, 48, 1494.
31. 1,1-Bis[4-(3,3-dimethyl-2-oxobutoxy)-3-methylphenyl]cyclopentane (10): White
crystals. Mp 68–70 °C. 1H NMR (500 MHz, CDCl3/d): 7.01 (s, 2H), 6.98 (dd,
J = 8.6, 2.6 Hz, 2H), 6.48 (d, J = 8.6 Hz, 2H), 4.81 (s, 4H), 2.24 (s, 6H), 2.22–2.18
(m, 4H), 1.67–1.65 (m, 4H), 1.24 (s, 18H). 13C NMR (125 MHz, CDCl3/d): 210.0,
154.1, 141.8, 129.8, 126.4, 124.8, 110.5, 69.6, 54.3, 43.2, 38.8, 26.4, 23.0, 16.6.
HRMS (FAB, [M+]) calcd for C31H42O4, 478.3083, found 478.3104.
32. Tagle, L. H.; Terraza, C. A.; Alvarez, P. Phosphorus Sulfur Silicon 2006, 181, 239.
33. Bis(3-methyl-4-(3,3-dimethyl-2-oxobutoxy)phenyl)dimethylsilane (11): White
crystals. Mp 120–122 °C. 1H NMR (500 MHz, CDCl3/d): 7.27 (s, 2H), 7.23 (d,
J = 7.9 Hz, 2H), 6.58 (d, J = 7.9 Hz, 2H), 4.87 (s, 4H), 2.28 (s, 6H), 1.25 (s, 18H),
0.46 (s, 6H); HRMS (FAB, m/z, [M]+) calcd for C28H40O4Si, 468.2696; found
468.2700.
11. Hashimoto, Y. Bioorg. Med. Chem. 2002, 10, 461.
12. Noguchi-Yachide, T.; Aoyama, A.; Makishima, M.; Miyachi, H.; Hashimoto, Y.
Bioorg. Med. Chem. Lett. 2007, 17, 3957.

S. Hosoda et al. / Bioorg. Med. Chem. Lett. 19 (2009) 3157–3161
3161
34. Bis(3-methyl-4-(3,3-dimethyl-2-oxobutoxy)phenyl)diethylsilane (12): White
crystals. Mp 88–91 °C. 1H NMR (500 MHz, CDCl3/d): 7.25 (s, 2H), 7.22 (d,
J = 8.5 Hz, 2H), 6.59 (d, J = 8.5 Hz, 2H), 4.87 (s, 4H), 2.28 (s, 6H), 1.26 (s, 18H),
0.99–0.97 (m, 10H); HRMS (FAB, m/z, [M]+) calcd for C30H44O4Si, 496.3009;
found 496.2995.
J = 8.5 Hz, 4H), 4.87 (s, 4H), 1.25 (s, 18H), 1.01–0.97 (m, 10H); HRMS (FAB,
[M+]) calcd for C28H40O4Si, 468.2696, found 468.2700.
36. (4-(3,3-Dimethyl-2-oxobutoxy)phenyl)(4-hydroxyphenyl)diethylsilane
(14):
Coloress oil. 1H NMR (500 MHz, CDCl3/d): 7.49 (d, J = 8.5 Hz, 2H), 7.36 (d,
J = 8.5 Hz, 2H), 6.89 (d, J = 8.5 Hz, 2H), 6.82 (d, J = 8.5 Hz, 2H), 4.89 (s, 2H), 4.79
(s, 1H), 1.26 (s, 9H), 1.02–0.95 (m, 10H); HRMS (FAB, [M+]) calcd for C22H30O3Si,
370.1964, found 370.1967.
35. Bis(4-(3,3-dimethyl-2-oxobutoxy)phenyl)diethylsilane (13): White crystals. Mp
40–42 °C. 1H NMR (500 MHz, CDCl3/d): 7.39 (d, J = 8.5 Hz, 4H), 6.85 (d,