<
KAKENHI> (C) (grant number 16K08325 to Y.S.) and a Grant-
in-aid for Scientific Research Young Scientists (B) (grant number
6K18924 to Y.H.) from Japan Society for Promotion of Science.
differentiation of neuronal progenitor cells. J. Med. Chem. 2017,
0, 2591-2596.
6
1
2. Mechelke, M. F.; Wiemer, D. F. Synthesis of farnesol analogues
through Cu(I)-mediated displacements of allylic THP ethers by
Grignard reagents. J. Org. Chem. 1999, 64, 4821–4829.
1
1
References and notes
13. Data for compound 2a: H NMR (400MHz, CDCl
(
3
) δ 8.09-8.05
m, 2H), 7.69-7.67 (m, 2H), 6.95-6.88 (m, 3H), 4.98 (dd, 2H, J=
7
2
2
.6, 15.2 Hz), 3.36 (d, 2H, J= 7.6 Hz), 3.17 (s, 2H), 2.26 (s, 3H),
.18 (s, 3H), 2.16 (s, 3H), 2.09 (dd, 2H, J= 7.4, 14.6 Hz), 1.99 (dd,
1
2
3
.
.
.
Presnell, S. R.; Stafford, D. W. The vitamin K-dependent
carboxylase. Thromb. Haemost. 2002, 87, 937–946.
13
H, J= 7.4, 14.6 Hz), 1.78 (s, 3H), 1.54 (s, 3H); C NMR (100
) δ 185.5, 184.6, 146.2, 143.4, 137.5, 136.7, 135.5,
35.2, 133.8, 133.44, 133.39, 132.26, 132.22, 130.9, 129.6, 126.4,
26.3, 125.5, 119.2, 42.9, 39.7, 26.6, 26.1, 21.0, 19.4, 16.5, 16.4,
Shearer, M. J.; Newman, P. Metabolism and cell biology of
vitamin K. Thromb Haemost. 2008, 100, 530–547.
MHz, CDCl
3
1
1
1
4
8
4
1
Schurgers, L.J.; Vermeer, C. Determination of Phylloquinone and
menaquinones in food. Effect of food matrix on circulating
vitamin K concentrations. Haemostasis, 2000, 30, 298-307.
Yamamoto, R.; Komai, M.; Kojima, K.; Furukawa, Y.; Kimura, S.
Menaquinone-4 accumulation in various tissues after an oral
administration of phylloquinone in Wistar rats. J. Nutr. Sci.
Vitaminol. 1997, 43, 133–143.
+
2.8; HRMS (M+H ) m/z calcd for C29
1
H
33
O
2
413.2481; found
13.2484. Data for compound 4a: H NMR (400MHz, CDCl ) δ
3
4
5
.
.
.10-8.06 (m, 2H), 7.69-7.67 (m, 2H), 7.01-6.88 (m, 3H), 5.19-
.95 (m, 2H), 3.39-3.35 (m, 2H), 3.23 (s, 1H), 3.14 (s, 1H), 2.24-
1
3
.96 (m, 13H), 1.80 and 1.78 (2s, 3H), 1.55 and 1.49 (2s, 3H);
) δ 185.6, 184.6, 146.22, 146.19, 143.4,
38.1, 137.8, 137.57, 137.51, 136.7, 136.3, 134.9, 134.0, 133.9,
C
NMR (100 Mz, CDCl
3
Okano, T.; Shimomura, Y.; Yamane, M.; Suhara, Y.; Kamao, M.;
Sugiura, M.; Nakagawa, K. Conversion of phylloquinone (vitamin
1
1
1
3
1
33.43, 133.38, 132.3, 132.2, 130.2, 129.5, 127.89, 127.81, 126.4,
26.3, 126.2, 125.8, 125.5, 125.2, 119.29, 119.23, 45.8, 43.8,
9.76, 39.71, 26.65, 26.59, 26.1, 20.8, 19.8, 19.4, 16.53,
K1) into menaquinone-4 (vitamin K
for menaquinone-4 accumulation in cerebra of mice. J. Biol. Chem.
008, 283, 11270–11279.
2
) in mice: two possible routes
2
+
6.49,16.47, 15.9, 15.2, 12.8; HRMS (M+H ) m/z calcd for
1
413.2481; found 413.2482. Data for compound 7a: H
6
7
.
.
Tabb, M. M.; Sun, A.; Zhou, C.; Grun, F.; Errandi, J.; Romero, K.;
Pham, H.; Inoue, S.; Mallick, S.; Lin, M.; Forman, B. M.;
C
29
H
33
O
2
NMR (400MHz, CDCl
3
) δ 8.09-8.06 (m, 2H), 7.69-7.67 (m, 2H),
.20-7.14 (m, 3H), 6.94-6.92 (m, 1H), 5.20-5.16 (m, 1H), 5.06-
2
Blumberg, B. Vitamin K regulation of bone homeostasis is
7
5
2
1
1
1
3
mediated by the steroid and xenobiotic receptor SXR. J. Biol.
Chem. 2003, 278, 43919–43927.
Ichikawa, T.; Horie-Inoue, K.; Ikeda, K.; Blumberg, B.; Inoue, S.
.02 (m, 1H), 3.38 (d, 2H, J= 6.8 Hz), 3.22 (s, 2H), 2.19 (s, 3H),
.14-2.09 (m, 2H), 2.05-2.01 (m, 2H), 1.80 (s, 3H), 1.51 (s, 3H),
1
3
3
.29 (s, 9H); C NMR (100 MHz, CDCl ) δ 185.6, 184.6, 151.0,
2
Steroid and xenobiotic receptor SXR mediates vitamin K -
activated transcription of extracellular matrix-related genes and
collagen accumulation in osteoblastic cells. J. Biol. Chem. 2006,
46.2, 143.5, 140.0, 137.6, 134.8, 133.45, 133.39, 132.3, 132.2,
27.9, 126.4, 126.3, 126.01, 125.96, 125.88, 122.8, 119.3, 46.5,
+
9.8, 34.6, 31.5, 26.7, 26.1, 16.5, 15.9, 12.8; HRMS (M+Na ) m/z
2
81, 16927–16934.
calcd for C31
compound 7b: H NMR (400MHz, CDCl
.683-7.675 (m, 2H), 7.21-7.17 (m, 3H), 6.97-6.94 (m, 1H), 5.18
t, 1H, J= 6.8 Hz), 5.08-5.00 (m, 2H), 3.37 (d, 2H, J= 6.8 Hz),
.24 (s, 2H), 2.19 (s, 3H), 2.10-1.94 (m, 8H), 1.80 (s, 3H), 1.57 (s,
H), 1.50 (s, 3H), 1.30 (s, 9H); 13C NMR (100 MHz, CDCl ) δ
H
36
1
O
2
Na 463.2613; found 463.2612. Data for
8
9
.
.
Li, J.; Lin, J. C.; Wang, H.; Peterson, J. W.; Furie, B. C.; Furie, B.;
Booth, S. L.; Volpe, J. J.; Rosenberg, P. A. Novel role of vitamin
K in preventing oxidative injury to developing oligodendrocytes
and neurons. J. Neurosci. 2003, 23, 5816–5826.
3
) δ 8.09-8.06 (m, 2H),
7
(
3
3
1
1
1
1
5
Suhara, Y.; Watanabe, M.; Nakagawa, K.; Wada, A.; Ito, Y.;
Takeda, K.; Takahashi, K.; Okano, T. Synthesis of novel vitamin
3
85.5, 184.6, 151.0, 146.2, 143.4, 140.1, 137.6, 135.2, 134.5,
33.42, 133.36, 132.3, 132.2, 127.9, 126.4, 126.3, 126.0, 125.9,
K analogues with modification at the ω-terminal position and
2
their biological evaluation as potent steroid and xenobiotic
receptor (SXR) agonists. J. Med. Chem. 2011, 54, 4269−4273.
24.1, 122.8, 119.2, 46.5, 39.8, 39.7, 34.6, 31.5, 26.8, 26.6, 26.1,
+
6.5, 16.1, 15.9, 12.8; HRMS (M+Na ) m/z calcd for C36
31.3239; found 531.3244.
44 2
H O Na
1
1
0. Suhara, Y.; Hirota, Y.; Hanada, N.; Nishina, S.; Eguchi, S.;
Sakane, R.; Nakagawa, K.; Wada, A.; Takahashi, K.; Tokiwa, H.;
Okano, T. Synthetic small molecules derived from natural vitamin
K homologues that induce selective neuronal differentiation of
neuronal progenitor cells. J. Med. Chem. 2015, 58, 7088−7092.
1. Kimura, K.; Hirota, Y.; Kuwahara, S.; Takeuchi, A.; Tode, C.;
Wada, A.; Osakabe, N.; Suhara, Y. Synthesis of novel synthetic
vitamin K analogues prepared by introduction of a heteroatom and
a phenyl group that induce highly selective neuronal
1
4. Hattori, T.; Takei, N.; Mizuno, Y.; Kato, K.; Kohsaka, S.
Neurotrophic and neuroprotective effects of neuron-specific
enolase on cultured neurons from embryonic rat brain. Neurosci.
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*
Corresponding author Tel: +81 48 720 6043.
E-mail address: suhara@shibaura-it.ac.jp (Y. Suhara).
#R.S., K.K., and Y.H. contributed equally.