Chemistry Letters 2002
15
OH
OMOM
O
OTBS
O
OH
O
OTBS
O
O
a, b, c
d
e
Et N
2
f
HO
Et N
2
O
O
OH
Cl
OMOM
OHC
OTBS
OH
OTBS
PhO S
PhO S
2
2
4
2
3
5
6
O
O
O
O
OMOM
O
O
OMOM
OH
O
OMOM
Cl
j
g
i
h
O
OMOM
O
OMOM
O
OMOM
R
n-Bu3Sn
O
O
O
O
10
8
9
11
7
O
O
OMOM
O
4
OMOM
OH
O
OMOM
Cl
Cl
Cl
Cl
Cl
Cl
k
l
m
O
OMOM
O
OMOM
O
OMOM
CH
2
R
R
R
O
O
13
14
12
=
R
O
OMOM
O
OMOM
O
OH
Cl
R
Cl
R
Cl
Cl
p
o
n
O
OMOM
O
OMOM
O
OH
R
O
O
O
( )-Napy
radiomycin A1
1:
15
16
ꢃ
Scheme 1. a) H2SO4/MeOH, reflux, 72 h, quant.ꢃb) TBSCl, NaH/THF, 0 C, 30 min, quant. c) Et2NH, Me3Al/PhMe, reflux,
ꢃ
10 h, quant. d) s-BuLi, TMEDA, DMF/THF,ꢃ-78 C, 1 h, quant. e) PhSO2Na/AcOH, 80 C, 12 h, 80%. f) MOMCl, i-Pr2NEt/
ꢃ
ꢃ
DMF, 0 C, 1 h, 88%. g) t-BuOLi/THF, -78 C – rt, 2 h. h) MnO2/CHCl3, rt, 30 min, 2 steps 64%. i) SO2Cl2/CH2Cl2, -40 C,
40 min, 77%. j) n-BuLi, CuI, LiBr/THF, -78 C, 1 h, 55%. k) NCS/1,2-dimethoxyethane, rt, 40 min, quant. l) KPh3BH/THF, -
78 C, 30 min, 61%. m) (PyS)2, n-Bu3P/PhMe, rt, 5 min, 76%. n) KPh3BH/THF, 0 C, 30 min, 72%. o) NCS, KHMDS/THF, -
ꢃ
ꢃ
ꢃ
5.35 (1H, d, J ¼ 7:0), 7.12 (1H, d, J ¼ 2:0), 7.28 (1H, d, J ¼ 2:0), 16.12
(1H, s), 13: 1H NMR ꢂ 1.18 (3H, s), 1.47 (3H, s), 1.51 (3H, s), 1.55 (3H,
s), 1.66 (3H, s), 1.68-1.83 (4H, m), 2.53 (1H, dd, J ¼ 14:5 and 8.0), 2.64
(1H, d, J ¼ 2:5), 2.72 (1H, dd, J ¼ 14:5 and 7.5), 3.48 (3H, s), 3.53 (3H,
s), 4.31 (1H, dd, J ¼ 2:5 and 2.5), 4.64 (1H, d, J ¼ 2:5), 4.90 (1H, dd,
J ¼ 8:0 and 7.5), 4.98 (1H, br s), 5.22 (1H, d, J ¼ 7:0), 5.26(1H, d,
J ¼ 7:0), 5.28 (1H, d, J ¼ 7:0), 5.29 (1H, d, J ¼ 7:0), 7.05 (1H, d,
J ¼ 2:0), 7.35 (1H, d, J ¼ 2:0), 14: 1H NMR (C6D6) ꢂ1.18 (3H, s), 1.43
(3H, s), 1.46(3H, s), 1.56(3H, d, J ¼ 1:0), 1.59 (3H, s), 1.82–1.98 (4H,
m), 2.55 (1H, dd, J ¼ 15:0 and 7.5), 2.68 (1H, dd, J ¼ 15:0 and 8.0),
2.98 (3H, s), 3.21 (3H, s), 4.25 (1H, d, J ¼ 2:0), 4.67 (1H, d, J ¼ 7:0),
4.68 (1H, d, J ¼ 7:0), 4.96(1H, d, J ¼ 6:5), 4.99 (1H, d, J ¼ 6:5), 5.04
(1H, m), 5.25 (1H, ddq, J ¼ 8:0, 7.5 and 1.0), 7.00 (1H, d, J ¼ 2:0), 7.17
(1H, d, J ¼ 2:0), 7.71 (1H, d, J ¼ 2:0), 15: 1H NMR (C6D6) ꢂ 1.28 (3H,
s), 1.38 (3H, s), 1.46(3H, s), 1.53 (3H, s), 1.67 (3H, d, J ¼ 1:0), 1.93-
2.07 (5H, m), 2.16(1H, ddd, J ¼ 14:0, 4.5 and 4.0), 2.51 (1H, dd,
J ¼ 14:5 and 7.5), 2.56(1H, dd, J ¼ 14:5 and 8.0), 3.01 (3H, s), 3.18
(1H, dd, J ¼ 13:0 and 4.0), 3.19 (3H, s), 3.47 (1H, dd, J ¼ 12:0 and 4.5),
4.72 (1H, d, J ¼ 6:5), 4.74 (1H, d, J ¼ 6:5), 4.93 (2H, s), 5.13 (1H, m),
5.33 (1H, dd, J ¼ 8:0 and 7.5), 7.21 (1H, d, J ¼ 2:0), 7.83 (1H, d,
J ¼ 2:0), 16: 1H NMR (C6D6) ꢂ 1.25 (3H, s), 1.38 (3H, s), 1.44 (6H, s),
1.58 (3H, s), 1.63–1.74 (4H, m), 2.41 (1H, dd, J ¼ 14:0 and 4.0), 2.54
(1H, dd, J ¼ 14:0 and 12.0), 2.99 (3H, s), 3.01 (1H, dd, J ¼ 13:5 and
7.5), 3.13 (1H, dd, J ¼ 13:5 and 9.0), 3.17 (3H, s), 4.53 (1H, dd,
J ¼ 12:0 and4.0), 4.67(1H, d, J ¼ 7:0), 4.69(1H, d, J ¼ 7:0), 4.88(1H,
d, J ¼ 6:0), 4.90 (1H, d, J ¼ 6:0), 4.95 (1H, m), 5.13 (1H, dd, J ¼ 9:0
and 7.5), 7.17 (1H, d, J ¼ 2:0), 7.73 (1H, d, J ¼ 2:0).
References and Notes
1
2
3
4
5
K. Shiomi, H. Iinuma, M. Hamada, H. Naganawa, M. Manabe, C.
Matsuki, T. Takeuchi, and H. Umezawa, J. Antibiot., 39, 487 (1986).
Y. Hori, Y. Abe, N. Shigematsu, T. Goto, M. Okuhara, and M. Kohsaka,
J. Antibiot., 46, 1890 (1993).
K. Shiomi, H. Nakamura, H. Iinuma, H. Naganawa, K. Isshiki, T.
Takeuchi, H. Umezawa, and Y. Iitaka, J. Antibiot., 39, 494 (1986).
K. Tatsuta, K. Akimoto, M. Annaka, Y. Ohno, and M. Kinoshita, Bull.
Chem. Soc. Jpn., 58, 1699 (1985).
K. Tatsuta, T. Yoshimoto, H. Gunji, Y. Okado, and M. Takahashi,
Chem. Lett., 2000, 646.
6K. Tatsuta, Adv. Synth. Catal., 2001, 143.
7
Selected data for key compounds: 1H NMR spectra (J in Hz; 400 and
600 MHz) were measured in CDCl3, unless otherwise noted. 1: 1H
NMR ꢂ 1.19 (3H, s), 1.33 (3H, s), 1.51 (3H, s), 1.52 (3H, s), 1.57-1.62
(4H, m), 1.63 (3H, s), 2.42 (1H, dd, J ¼ 14:0 and 11.0), 2.48 (1H, dd,
J ¼ 14:0 and 5.0), 2.70 (2H, br d, J ¼ 8:0), 4.43 (1H, dd, J ¼ 11:0 and
5.0), 4.71 (1H, t, J ¼ 8:0), 4.91 (1H, m), 6.21 (1H, br s), 6.70 (1H, d,
J ¼ 2:5), 7.16(1H, d, J ¼ 2:5), 11.83 (1H, s); IR (KBr) 1700, 1641,
1614, 1253, 1076 cmꢂ1, 3: 1H NMR ꢂ 0.19 (6H, s), 0.21 (6H, s), 0.95
(9H, s), 0.97 (9H, s), 0.98 (3H, t, J ¼ 7:0), 1.22 (3H, t, J ¼ 7:0), 3.02-
3.31 (2H, m), 3.35-3.69 (2H, m), 6.31 (1H, d, J ¼ 2:0), 6.47 (1H, dd,
J ¼ 8:0 and 2.0), 7.04 (1H, d, J ¼ 8:0), 6: mp 117–118 ꢃC; 1H NMR ꢂ
3.48 (3H, s), 3.53 (3H, s), 5.25 (1H, d, J ¼ 7:0), 5.27 (1H, d, J ¼ 7:0),
5.30 (1H, d, J ¼ 7:0), 5.35 (1H, d, J ¼ 7:0), 6.01 (1H, s), 6.93 (1H, d,
J ¼ 2:0), 7.19 (1H, d, J ¼ 2:0), 7.54 (2H, ddd, J ¼ 7:5, 7.5 and 1.5),
7.68 (1H, dddd, J ¼ 7:5, 7.5, 1.5 and 1.5), 7.89 (2H, dd, J ¼ 7:5 and
1.5), 8: mp 123–124 ꢃC; 1H NMR ꢂ 1.57 (6H, s), 2.72 (2H, s), 3.49 (3H,
s), 3.53 (3H, s), 5.27 (2H, s), 5.29 (2H, s), 7.16(1H, d, J ¼ 2:5), 7.41
(1H, d, J ¼ 2:5), 9: 1H NMR ꢂ 1.59 (3H, s), 1.70 (3H, s), 3.49 (3H, s),
3.54 (3H, s), 4.16(1H, s), 5.28 (2H, s), 5.30 (2H, s), 7.18 (1H, d,
J ¼ 2:5), 7.44 (1H, d, J ¼ 2:5), 11: 1H NMR ꢂ 1.15 (3H, s), 1.45 (3H, d,
J ¼ 1:5), 1.57 (3H, s), 1.59 (3H, s), 1.69 (3H, s), 1.95–2.06(4H, m), 2.38
(1H, dd, J ¼ 14:0 and 8.0), 2.46(1H, dd, J ¼ 14:0 and 7.5), 3.50 (3H, s),
3.57 (3H, s), 4.42 (1H, s), 5.04 (1H, m), 5.10 (1H, ddq, J ¼ 8:0, 7.5 and
1.5), 5.26(1H, d, J ¼ 7:0), 5.28 (1H, d, J ¼ 7:0), 5.33 (1H, d, J ¼ 7:0),
8
9
P. Beak and R. A. Brown, J. Org. Chem., 42, 1823 (1977).
D. Obrecht, Helv. Chim. Acta, 74, 27 (1991).
10 Y. Naruta and K. Maruyama, Chem. Lett., 1979, 881.
11 N. M. Yoon, K. E. Kim, and J. Kang, J. Org. Chem., 51, 226(1986).
12 M. Goldbach, E. Jakel, and M. P. Schneider, J. Chem. Soc., Chem.
¨
Commun., 1987, 1434.
13 The authentic sample of natural napyradiomycin A1 was kindly
provided by Dr. H. Naganawa, Institute of Microbial Chemistry.