First Syntheses of Caerulomycin E and Collismycins A and C. A New Synthesis of Caerulomycin A

Article abstract of DOI:10.1021/jo972022i

Caerulomycins produced by Streptomyces caeruleus, and collismycins more recently isolated from Streptomyces species, are bipyridinic molecules endowed with antibiotic and cytotoxic activities. The first syntheses of caerulomycin E (1), as well as new synt

Full text of DOI:10.1021/jo972022i

2892
J . Org. Chem. 1998, 63, 2892-2897
F ir st Syn th eses of Ca er u lom ycin E a n d Collism ycin s A a n d C. A
New Syn th esis of Ca er u lom ycin A
Franc¸ois Tre´court, Bruno Gervais, Olivier Mongin, Catherine Le Gal, Florence Mongin, and
Guy Que´guiner*
Laboratoire de Chimie Organique Fine et He´te´rocyclique, IRCOF, UPRESA 6014, Place E. Blondel,
BP 08 76131 Mont-Saint-Aignan Ce´dex, France
Received November 4, 1997
Caerulomycins produced by Streptomyces caeruleus, and collismycins more recently isolated from
Streptomyces species, are bipyridinic molecules endowed with antibiotic and cytotoxic activities.
The first syntheses of caerulomycin E (1), as well as new syntheses of caerulomycin A (2), are
reported. Methodologies involving efficiently controlled reactions such as metalation and cross-
coupling reactions have been developed from 2,2′-bipyridine. The functionalization at C-6 could
be achieved by metalation of 2,2′-bipyridine N-oxides 5 and 12. 6-Halo-4-methoxy-2,2′-bipyridines
(6, 10, 11) became key-molecules of these different pathways, and further functionalization at C-5
allowed the first syntheses of collismycins A (3) and C (4).
In tr od u ction
structure is also present as in the earlier reported
orelline12 and caerulomycin C.13 Here we describe the
first syntheses of 1, 3, and 4 and a new synthesis of 2
starting from 2,2′-bipyridine. The strategy mainly in-
volves efficiently controlled reactions such as metalation
and cross-coupling reactions.
Caerulomycins E (1) and A (2) are two of the five
caerulomycins produced by Streptomyces caeruleus.1 Cae-
rulomycin A (2), a bipyridinic molecule with antibiotic
properties,2,3 was first isolated2a in 1959 and its structure
was elucidated4 in 1967; two syntheses of compound 2
have been previously reported by Divekar5 and De
Souza.6
Collismycins A (3) and C (4) were isolated in 1993 by
Gomi7 from Streptomyces sp. SF 2738 and their struc-
tures established. Collismycin A (3) was independently
isolated by Shindo8 from Streptomyces sp. MQ 22.9 These
compounds are endowed with antibiotic and cytotoxic
activities.7,8
Because of our interest in the synthesis of pyridine-
containing natural products10 and in the light of our
knowledge of the metalation field,11 we undertook the
synthesis of compounds 1-4 in which a 2,2′-bipyridyl
* To whom correspondence should be addressed. Phone: + 33 (0)
2 35 52 29 00. Fax: + 33 (0) 2 35 52 29 62. E-mail: guy.queguiner@
ircof.insa-rouen.fr.
Resu lts a n d Discu ssion
(1) Vining, L. C.; McInnes, A. G.; McCulloch, A. W.; Smith, D. G.;
Walter, J . A. Can. J . Chem. 1988, 66, 191, and references therein.
(2) (a) Funk, A.; Divekar, P. V. Can. J . Microbiol. 1959, 5, 317. (b)
Chandran, R. R.; Sankaran, R.; Divekar, P. V. J . Antibiot. 1968, 21,
243.
(3) Chatterjee, D. K.; Raether, W.; Iyer, N.; Ganguli, B. N. Z.
Parasitenkd 1984, 70, 569.
(4) Divekar, P. V.; Read, G.; Vining, L. C. Can. J . Chem. 1967, 45,
1215.
(5) Ranganathan, S.; Singh, B. B.; Divekar, P. V. Can. J . Chem.
1969, 47, 165.
(6) (a) Alreja, B. D.; Kattige, S. L.; Lal, B.; De Souza, N. J .
Heterocycles 1986, 24, 1637. (b) Alreja, B. D.; Kattige, S. L.; De Souza,
N. J . (Hoechst A.-G.) Ger. Offen. DE 3,414,830, 31 Oct 1985, Appl. 19
Apr 1984; Chem. Abstr. 1986, 104, 207056j. (c) Alreja, B. D.; Kattige,
S. L.; De Souza, N. J . (Hoechst India Ltd.) India IN 157,619, 03 May
1986, Appl. 04 J an 1984; Chem. Abstr. 1987, 106, 49882k.
(7) (a) Gomi, S.; Amano, S.; Sato, E.; Miyadoh, S.; Kodama, Y. J .
Antibiot. 1994, 47, 1385, and references therein. (b) Gomi, S.; Ito, O.;
Ajito, Y.; Amano, S.; Sato, E.; Karya, H.; Koyama, M. (Meiji Seika Co.)
J pn. Kokai Tokkyo Koho J P 0578,322 [9378,322], 30 Mar 1993, Appl.
20 Sep 1991; Chem. Abstr. 1993, 119, 135507s.
Starting from 2,2′-bipyridine N-oxide, functionalization
at C-4 and C-6 could be investigated by two different
routes (Scheme 1): route A (functionalization at C-4 first
then C-6) and route B (functionalization at C-6 first then
C-4) allowed suitably disubstituted 2,2′-bipyridines for
the synthesis of caerulomycins 1 and 2. Subsequent
functionalization at C-5 could afford collismycins 3 and
4. The target bipyridines could be synthesized from
6-halo-4-methoxy-2,2′-bipyridines (Z ) Cl, Br, I).
(10) (a) Godard, A.; Marsais, F.; Ple´, N.; Tre´court, F.; Turck, A.;
Que´guiner, G. Heterocycles 1995, 40, 1055. (b) Tre´court, F.; Mallet,
M.; Mongin, O.; Que´guiner, G. J . Org. Chem. 1994, 59, 6173. (c)
Tre´court, F.; Mallet, M.; Mongin, O.; Que´guiner, G. J . Heterocycl. Chem.
1995, 32, 1117.
(11) For a review on directed ortho metalation of pyridines and some
other π-deficient azaaromatics, see: Que´guiner, G.; Marsais, F.;
Snieckus, V.; Epsztajn, J . Adv. Heterocycl. Chem. 1991, 52, 187.
(12) Tre´court, F.; Mallet, M.; Mongin, O.; Gervais, B.; Que´guiner,
G. Tetrahedron 1993, 49, 8373.
(8) Shindo, K.; Yamagishi, Y.; Okada, Y.; Kawai, H. J . Antibiot.
1994, 47, 1072.
(9) The name of collismycin was given to this family of compounds
(13) Tre´court, F.; Gervais, B.; Mallet, M.; Que´guiner, G. J . Org.
Chem. 1996, 61, 1673.
by Shindo,8 whereas Gomi7 used the name SF 2738.
S0022-3263(97)02022-7 CCC: $15.00 © 1998 American Chemical Society
Published on Web 04/08/1998

First Syntheses of Caerulomycin E and Collismycins A and C
J . Org. Chem., Vol. 63, No. 9, 1998 2893
Sch em e 1
Sch em e 2
Ta ble 1. Meta la tion of 5
product (E),
% yield
Route A was first investigated. 4-Methoxy-2,2′-bipyr-
idine N-oxide (5) was easily prepared from 2,2′-bipyridine
by a three-step sequence described in the literature.14
Reductive chlorination15 of 5 using POCl3 at reflux gave
6-chloro-4-methoxy-2,2′-bipyridine (6) in an almost quan-
titative yield, whereas its reductive bromination using
entry
base
t, h
1 h
1 h
1 h
electrophile
1
2
3
4
LDAa
LDAa
LDAa
LTMPb
DCl/D2O
BrCN
I2
7 (D), 80
8 (Br), 15
9 (I), 70
9 (I), 94
1.5 h
I2
a
b
2 equiv was used. 1 equiv was used.
16
either POBr3 or the mixture POBr3/PBr5 never gave
6-bromo-4-methoxy-2,2′-bipyridine (10) (Scheme 2). An-
other way had to be found to obtain compounds 10 and
11. Recently, we reported some results about metalation
in the pyridine N-oxide series.17 Metalation of 5 using
LDA or LTMP at -70 °C occurred at C-6 as demonstrated
by the lithio derivative quenching with concd DCl (Table
1, entry 1). The trapping with dibromoethane completely
failed whereas using BrCN as electrophile could give a
poor yield (15%) of 6-bromo-4-methoxy-2,2′-bipyridine
N-oxide (8). Trapping with iodine gave a very good yield
(Table 1, entry 4) of 6-iodo-4-methoxy-2,2′-bipyridine
N-oxide (9). Bromo and iodo N-oxides 8 and 9 were
successfully reduced with PBr3 into 10 and 11 (Scheme
2).
Sch em e 3
Sch em e 4
Using route A, it was thus possible to prepare 6-chloro-,
6-bromo-, and 6-iodo-4-methoxy-2,2′-bipyridines 6, 10,
and 11 in 43%, 6%, and 27% overall yield, respectively,
from 2,2′-bipyridine.
Route B was then investigated in order to improve the
yield of 10 which largely depends on the metalation step.
Metalation of 2,2′-bipyridine N-oxide (12) with LDA at
-70 °C was successfully employed. When the lithio
derivative was quenched by BrCN, 6-bromo-2,2′-bipyri-
dine N-oxide (13) was obtained with a satisfying yield of
70% along with 5,6-dibromo- and 4,5,6-tribromo-2,2′-
bipyridine N-oxides in 12 and 8% yield, respectively. Note
that with iodine, only compound 14 was obtained (Scheme
3).
Nitration at temperature not exceeding 80 °C was fol-
lowed by substitution of the nitro group with MeONa
under mild conditions. Finally, reduction of the N-oxides
using PBr3 gave 10 and 11 in quite good yields. Note
that in the case of the bromo compound 8, a mixture of
6-bromo and 6-chloro derivatives was obtained when
using PCl3 instead of PBr3 (Scheme 4).
6-Bromo- and 6-iodo-4-methoxy-2,2′-bipyridines 10 and
11 were then prepared in a classical three-step sequence.
(14) Wenkert, D.; Woodward, R. B. J . Org. Chem. 1983, 48, 283.
(15) (a) Rokach, J .; Girard, Y. J . Heterocycl. Chem. 1978, 15, 683.
(b) Newkome, G. R.; Garbis, S. J . J . Heterocycl. Chem. 1978, 15, 685.
(16) Attempts to obtain 10 by treatment of 4-methoxy-(2,2′-bipyri-
din)-6(1H)-one with the mixture POBr3/PBr5 also failed.
(17) Mongin, O.; Rocca, P.; Thomas-dit-Dumont, L.; Tre´court, F.;
Marsais, F.; Godard, A.; Que´guiner, G. J . Chem. Soc., Perkin Trans. 1
1995, 2503, and references therein.
Using route B, it was possible to obtain 10 and 11 in
28% and 6% overall yield, respectively. Thus, for the
synthesis of 6-halo-4-methoxy-2,2′-bipyridines, route A
is particularly suitable to prepare chloro and iodo deriva-
tives 6 and 11, and route B should be preferred to prepare
bromo compound 10.

2894 J . Org. Chem., Vol. 63, No. 9, 1998
Tre´court et al.
Sch em e 5
Different pathways were then investigated to reach
caerulomycin E (1). 6-Chloro-4-methoxy-2,2′-bipyridine
(6) was coupled18 with an excess of methylzinc chloride
in the presence of a catalytic amount of tetrakis(triphen-
ylphosphine)palladium(0)19 to afford the methylpyridine
17 in an almost quantitative yield. A similar result was
obtained from 6-bromo-4-methoxy-2,2′-bipyridine (10).
Caerulomycin E (1) could be prepared by oxidation of 17,
using benzeneseleninic anhydride (BSA)20 (64%) or freshly
21
prepared SeO2 (60%). Caerulomycin E (1) could also
be prepared in two steps starting from compound 17. The
possible metalation of the methyl group22 of picolines led
in our case to the dithioketal 18; subsequent treatment
with BF3‚Et2O and HgO23 also afforded 1 in 30% overall
yield.
Moreover, the chelate BuLi-TMEDA can easily per-
form an iodine-lithium exchange on 6-iodo compound 11
at low temperature. The lithio derivative was quenched
by concd DCl to yield 6-deuterio-4-methoxy-2,2′-bipyri-
dine (19, 86%) and by ethyl formate to give caerulomycin
E (1).
Reacting the aldehyde 1 with hydroxylamine afforded
the (E/Z) 91:9 mixture of oximes. Single recrystallization
gave pure caerulomycin A (2) (Scheme 5). Thus, the best
synthesis of caerulomycin E (1) involves a six-step
sequence in a 26% overall yield, calculated from 2,2′-
bipyridine via 6-chloro-4-methoxy-2,2′-bipyridine (6).
To reach collismycins 3 and 4, functionalization at C-5
could be investigated either from caerulomycin E (1) or
halo derivatives 6, 10, and 11. The metalation conditions
described by Comins24 for various aldehydes by using
lithium N,N,N′-trimethylethylenediamide was tested on
compound 1 but failed. It was also possible to attempt
the other Comins experimental conditions25 using N-
formyl-N,N′,N′-trimethylethylenediamine on the lithio
derivative prepared from 6-bromo and 6-iodo derivatives
10 and 11. Under these conditions, induced metalation
at C-5 was never observed, and only caerulomycin E (1)
was obtained.
The metalation of 6-halo-4-methoxy-2,2′-bipyridines (6,
10, 11) was then studied. This deprotonation could occur
at C-3 or C-5. We observed that from 4-methoxy-2,2′-
bipyridine, the 3-lithio derivative26 was prepared with
LDA at -70 °C. On the other hand, the 5-lithio deriva-
tives of 6 and 10 were obtained under the same condi-
tions, as demonstrated by quenching with concd DCl.
These experiments show that chlorine and bromine
(directing groups) exhibit a stronger effect than the
pyridine ring does. To reach the target molecule 3,
methyl disulfide was used as electrophile,27 but the
conditions had to be carefully optimized to avoid side
replacement of the halogen at C-6 by a methylthio moiety
before hydrolysis. Similar results were observed when
using 6-iodo-4-methoxy-2,2′-bipyridine (11) instead of
bromo compound 10 (Scheme 6, Table 2).
The strategy used for the functionalization at C-6 was
a halogen-lithium exchange. The chelate BuLi-TME-
DA could in this case perform a bromine-lithium ex-
change from compound 23. The lithio derivative was
then quenched by DMF to give 25. Reacting aldehyde
25 with hydroxylamine afforded collismycin A (3) as the
(E)-oxime. Moreover, reduction of 25 with NaBH4 af-
forded quantitatively collismycin C (4) (Scheme 7).
Thus, collismycins A (3) and C (4) could be synthesized
in eight steps and 7% overall yield, and eight steps and
9% overall yield, respectively, starting from 2,2′-bipyri-
dine via 6-bromo-4-methoxy-2,2′-bipyridine (10).
(18) Erdik, E. Tetrahedron 1992, 48, 9577.
(19) Coulson, D. R. Inorg. Synth. 1972, 13, 121.
(20) Barton, D. H. R.; Hui, R.; Ley, S. V. J . Chem. Soc., Perkin Trans.
1 1982, 2179.
(21) (a) Burger, A.; Modlin J r., L. R. J . Am. Chem. Soc. 1940, 62,
1079. (b) Kaplan, H. J . Am. Chem. Soc. 1941, 63, 2654.
(22) Beumel J r., O. F.; Smith, W. N.; Rybalka, B. Synthesis 1974,
43.
Con clu sion
(23) (a) Vedejs, E.; Fuchs, P. L. J . Org. Chem. 1971, 36, 366. (b)
Corey, E. J .; Erickson, B. W. J . Org. Chem. 1971, 36, 3553.
(24) Comins, D. L. Synlett 1992, 615.
(25) Comins, D. L.; Hong, H.; Saha, J . K.; J ianhua, G. J . Org. Chem.
1994, 59, 5120.
(26) Gervais, B. Unpublished results (1994).
(27) Turner, J . A. J . Org. Chem. 1983, 48, 3401.
This first synthesis of caerulomycin E needed only six
steps starting from commercially available 2,2′-bipyridine
via 6-chloro-4-methoxy-2,2′-bipyridine (6) with an overall
yield of 26%. We considerably improved (20% from 2,2′-
bipyridine) the overall yield of the total synthesis of

First Syntheses of Caerulomycin E and Collismycins A and C
J . Org. Chem., Vol. 63, No. 9, 1998 2895
Na. The water content of the solvents was estimated to be
lower than 45 ppm by the modified Karl Fischer method.28
Commercial solutions of butyllithium (BuLi) and methylzinc
chloride were employed as received. Pd(PPh3)4 was synthe-
sized by literature method.19 Metalations and cross coupling
reactions were carried out under dry argon.
Sch em e 6
All solutions were dried over MgSO4, the solvents were
evaporated under reduced pressure, and unless otherwise
noted, the crude compound was chromatographed on a silica
gel column (eluent is given in the product description).
4-Meth oxy-2,2′-bip yr id in e N-Oxid e (5).14 A three-step
sequence14 from 2,2′-bipyridine gave 5 by N-oxidation, nitra-
tion, and substitution of 4-nitro by MeONa [(1) m-CPBA/
CHCl3/25 °C/13 h: 79%; (2) KNO3/H2SO4/110 °C/2.5 h: 65%;
(3) MeONa/MeOH/40 °C/30 min: 88%].
6-Ch lor o-4-m eth oxy-2,2′-bip yr id in e (6). 4-Methoxy-2,2′-
bipyridine N-oxide monohydrate (5‚H2O, 1.0 g, 4.5 mmol) was
added to POCl3 (60 mL) and heated under reflux for 5 h.
Solvent removal, addition of water (50 mL), neutralization with
K2CO3, and extraction with CH2Cl2 (3 × 20 mL) afforded 96%
of 6 (eluent: CH2Cl2/Et2O 80:20): mp 78 °C; 1H NMR (CDCl3)
δ 3.89 (s, 3H), 6.81 (d, 1H, J ) 1.9 Hz), 7.29 (ddd, 1H, J ) 7.6,
4.5, 1.6 Hz), 7.76 (td, 1H, J ) 7.6, 1.8 Hz), 7.89 (d, 1H, J ) 1.9
Hz), 8.35 (dd, 1H, J ) 7.6, 1.6 Hz), 8.61 (dd, 1H, J ) 4.5, 1.8
Hz); IR (KBr) 1550, 1408, 1319, 1219, 1142, 1038. Anal. Calcd
for C11H9ClN2O (220.66): C, 59.88; H, 4.11; N, 12.70. Found:
C, 60.02; H, 3.92; N, 12.69.
Ta ble 2. Meta la tion of 6 a n d 10
product,
% yield
entry
X
conditions
1
2
3
Cl
Br
Br
-70 °C/0.5 ha
-70 °C/5 mina
-70 °C/5 minb
22, 98
23, 61
23, 6; 24, 44
Gen er a l P r oced u r e A: Meta la tion of 4-Meth oxy-2,2′-
bip yr id in e N-Oxid e (5). BuLi (1.4 mmol) in hexane (0.54
mL) was added to a solution of diisopropylamine (0.19 mL,
1.4 mmol) in THF (5 mL) at 0 °C. The solution of LDA was
cooled to -70 °C, and a solution of 4-methoxy-2,2′-bipyridine
N-oxide monohydrate (5‚H2O, 0.10 g, 0.45 mmol) in THF (5
mL) was added. After 1 h at this temperature, the electrophile
was added and allowed to react as mentioned in the product
description. The solution was hydrolyzed with water (10 mL)
and extracted with CH2Cl2 (3 × 10 mL).
Immediate workup after raising to room temperature. b Work-
up after 13 h at room temperature.
a
Sch em e 7
6-Deu ter io-4-m eth oxy-2,2′-bip yr id in e N-Oxid e (7). The
general procedure A, using concd DCl (2 mL) in THF (5 mL)
at -70 °C, gave 7 (eluent: AcOEt): deuterium incorporation:
80%;29 1H NMR (CDCl3) δ 3.94 (s, 3H), 6.87 (d, 1H, J ) 3.6
Hz), 7.38 (dd, 1H, J ) 7.8, 4.7 Hz), 7.77 (d, 1H, J ) 3.6 Hz),
7.87 (td, 1H, J ) 7.8, 1.9 Hz), 8.75 (dd, 1H, J ) 4.7, 1.9 Hz),
9.07 (d, 1H, J ) 7.8 Hz).
6-Br om o-4-m eth oxy-2,2′-bip yr id in e N-Oxid e (8). The
general procedure A, using a solution of BrCN (0.11 g, 1.0
mmol) in THF (5 mL) at -70 °C with stirring for 15 min, gave
15% of 8 (eluent: AcOEt): mp 79 °C; 1H NMR (CDCl3) δ 3.91
(s, 3H), 7.26 (d, 1H, J ) 3.6 Hz), 7.35 (ddd, 1H, J ) 7.7, 4.7,
1.2 Hz), 7.72 (d, 1H, J ) 3.6 Hz), 7.81 (td, 1H, J ) 7.7, 1.8
Hz), 8.69 (dd, 1H, J ) 4.7, 1.8 Hz), 8.93 (dd, 1H, J ) 7.7, 1.2
Hz); IR (KBr) 1614, 1585, 1396, 1223, 1142, 1023. Anal. Calcd
for C11H9BrN2O2 (281.11): C, 47.00; H, 3.23; N, 9.97. Found:
C, 47.26; H, 3.06; N, 10.34. F r om 15. A solution of MeONa
(65 mg, 1.2 mmol) in MeOH (10 mL) was added to a suspension
of 6-bromo-4-nitro-2,2′-bipyridine N-oxide (15, 0.30 g, 1.0
mmol) in MeOH (5 mL) at 25 °C. The mixture was heated for
30 min at 40 °C, cooled, and hydrolyzed with water (10 mL).
Extraction with CH2Cl2 (3 × 15 mL) afforded 84% of 8.
6-Iod o-4-m eth oxy-2,2′-bip yr id in e N-Oxid e (9). The gen-
eral procedure A, using a solution of iodine (0.25 g, 1.0 mmol)
in THF (5 mL) at -70 °C with stirring for 1 h, gave 9 (eluent:
AcOEt). Before extraction, the solution was treated with
Na2S2O3 until bleaching. Yield: 94% when LTMP (1 equiv)
was used instead of LDA and the metalation time extended
to 1.5 h; mp 118 °C; 1H NMR (CDCl3) δ 3.90 (s, 3H), 7.33 (ddd,
1H, J ) 8.0, 4.7, 1.2 Hz), 7.49 (d, 1H, J ) 3.5 Hz), 7.74 (d, 1H,
J ) 3.5 Hz), 7.83 (td, 1H, J ) 8.0, 1.9 Hz), 8.69 (ddd, 1H, J )
4.7, 1.9, 1.0 Hz), 8.91 (ddd, 1H, J ) 8.0, 1.2, 1.0 Hz); IR (KBr)
1609, 1475, 1393, 1222, 1140, 1024. Anal. Calcd for C11H9IN2O2
(328.11): C, 40.27; H, 2.76; N, 8.54. Found: C, 40.23; H, 2.50;
caerulomycin A previously described by Divekar5 (two
steps, 8% yield from 5) and also De Souza6 (four steps,
5% yield).
For the synthesis of collismycins A and C, the strategy
successfully involved a metalation reaction to introduce
the methylthio moiety at C-5.
Exp er im en ta l Section
(28) Bizot, J . Bull. Soc. Chim. Fr. 1967, 151.
(29) Deuterium incorporation was determined from the 1H NMR
integration values.
Gen er a l. Spectroscopic experiments were made as recently
reported.13 THF and Et2O were distilled from benzophenone/

2896 J . Org. Chem., Vol. 63, No. 9, 1998
Tre´court et al.
N, 8.41. F r om 16. As previously described for the synthesis
of compound 8 from 15. Yield: 83%.
4-Meth oxy-6-m eth yl-2,2′-bip yr id in e (17). A solution of
methylzinc chloride (6.0 mmol) in THF (15 mL) was added to
a solution of 6-chloro- or 6-bromo-4-methoxy-2,2′-bipyridine (6
or 10, 1.0 mmol) and Pd(PPh3)4 (50 mg, 0.040 mmol) in THF
(10 mL). The mixture was refluxed for 40 h and then poured
onto an aqueous solution (20 mL) of EDTA (2.5 g). Neutral-
ization with K2CO3 and extraction with Et2O (3 × 10 mL)
afforded 17 (eluent: Et2O); yield: 95% from 6, 90% from 10;
6-Br om o-4-m eth oxy-2,2′-bip yr id in e (10). PBr3 (0.29 mL,
3.0 mmol) was slowly added to a stirred solution of 6-bromo-
4-methoxy-2,2′-bipyridine N-oxide (8, 0.28 g, 1.0 mmol) in
CHCl3 (10 mL) at 25 °C. The mixture was refluxed for 45 min,
cooled, and poured onto ice. After neutralization with K2CO3
and extraction with CH2Cl2 (3 × 10 mL), 90% of 10 was
obtained (eluent: CH2Cl2): mp 84 °C; 1H NMR (CDCl3) δ 3.93
(s, 3H), 7.01 (d, 1H, J ) 2.1 Hz), 7.30 (ddd, 1H, J ) 7.8, 4.8,
1.2 Hz), 7.80 (td, 1H, J ) 7.8, 1.8 Hz), 7.94 (d, 1H, J ) 2.1
Hz), 8.39 (dd, 1H, J ) 7.8, 1.2 Hz), 8.65 (dd, 1H, J ) 4.8, 1.8
Hz); IR (KBr) 1583, 1542, 1459, 1402, 1311, 1216, 1140, 1029.
Anal. Calcd for C11H9BrN2O (265.11): C, 49.84; H, 3.42; N,
10.57. Found: C, 49.94; H, 3.38; N, 10.55.
1
mp 57 °C; H NMR (CDCl3) δ 2.57 (s, 3H), 3.91 (s, 3H), 6.69
(d, 1H, J ) 2.3 Hz), 7.28 (dd, 1H, J ) 8.0, 4.7 Hz), 7.77 (d, 1H,
J ) 2.3 Hz), 7.78 (td, 1H, J ) 8.0, 1.8 Hz), 8.40 (dd, 1H, J )
8.0, 1.2 Hz), 8.65 (dd, 1H, J ) 4.7, 1.8 Hz); IR (KBr) 3000,
1582, 1462, 1413, 1345, 1202, 1043. Anal. Calcd for C12H12N2O
(200.24): C, 71.98; H, 6.04; N, 13.99. Found: C, 71.97; H, 6.09;
N, 13.82.
6-Iod o-4-m eth oxy-2,2′-bip yr id in e (11). From 6-iodo-4-
methoxy-2,2′-bipyridine N-oxide (9), as previously described
for the synthesis of compound 10. Yield: 64%; mp 110 °C; 1H
NMR (CDCl3) δ 3.92 (s, 3H), 7.25 (d, 1H, J ) 2.2 Hz), 7.30
(ddd, 1H, J ) 7.8, 4.8, 1.1 Hz), 7.78 (td, 1H, J ) 7.7, 1.7 Hz),
7.93 (d, 1H, J ) 2.2 Hz), 8.37 (dd, 1H, J ) 8.0, 0.8 Hz), 8.63
(dd, 1H, J ) 4.8, 1.7 Hz); IR (KBr) 2960, 1578, 1543, 1416,
1393, 1319, 1212, 1040. Anal. Calcd for C11H9IN2O (312.11):
C, 42.33; H, 2.91; N, 8.98. Found: C, 42.48; H, 2.85; N, 8.90.
Gen er a l P r oced u r e B: Meta la tion of 2,2′-Bip yr id in e
N-Oxid e (12). BuLi (12 mmol) in hexane (4.8 mL) was added
to a solution of diisopropylamine (1.7 mL, 12 mmol) in THF
(25 mL) at 0 °C. The solution of LDA was added to a solution
of 2,2′-bipyridine N-oxide (12, 1.0 g, 6.0 mmol) in THF (25 mL)
at -70 °C. After 30 min at this temperature, the electrophile
(13 mmol) was added and allowed to react as mentioned in
the product description. The solution was hydrolyzed with
water (10 mL) and extracted with CH2Cl2 (3 × 20 mL).
6-Br om o-2,2′-bip yr id in e N-Oxid e (13). The general pro-
cedure B, using a solution of BrCN in THF (10 mL) at -70 °C
with stirring for 15 min, gave 70% of 13 (eluent: Et2O): mp
89.5 °C; 1H NMR (CDCl3) δ 7.18 (t, 1H, J ) 7.9 Hz), 7.35 (ddd,
1H, J ) 8.0, 5.2, 1.5 Hz), 7.68 (dd, 1H, J ) 7.9, 2.1 Hz), 7.80
(td, 1H, J ) 8.0, 1.8 Hz), 8.12 (dd, 1H, J ) 7.9, 2.1 Hz), 8.69
(dd, 1H, J ) 5.2, 1.8 Hz), 8.83 (dd, 1H, J ) 8.0, 1.5 Hz); IR
(KBr) 2361, 1560, 1458, 1423, 1368, 1259, 1135. Anal. Calcd
for C10H7BrN2O (251.09): C, 47.84; H, 2.81; N, 11.16. Found:
C, 47.54; H, 2.64; N, 11.06.
6-[Bis(p h en ylt h io)m et h yl]-4-m et h oxy-2,2′-b ip yr id in e
(18). BuLi (20 mmol) in hexane (8.1 mL) was added to a
solution of 2,2,6,6-tetramethylpiperidine (3.4 mL, 20 mmol)
in THF (50 mL) at 0 °C. The solution of LTMP was added to
a solution of 4-methoxy-6-methyl-2,2′-bipyridine (17, 1.0 g, 5.0
mmol) in THF (30 mL) at -70 °C. After 1.2 h at this
temperature, phenyl disulfide (4.9 g, 22 mmol) in THF (20 mL)
was added. Stirring for 3 h at -70 °C, addition of water (20
mL) and extraction with CH2Cl2 (3 × 20 mL) gave 76% of 18
1
(eluent: CH2Cl2/Et2O 80:20): mp 82 °C; H NMR (CDCl3) δ
3.86 (s, 3H), 5.68 (s, 1H), 6.86 (d, 1H, J ) 2.3 Hz), 7.4 (m,
11H), 7.79 (td, 1H, J ) 7.9, 1.8 Hz), 7.87 (d, 1H, J ) 2.3 Hz),
8.38 (dd, 1H, J ) 7.9, 0.9 Hz), 8.66 (dd, 1H, J ) 4.7, 1.8 Hz);
IR (KBr) 3055, 1597, 1582, 1561, 1425, 1349, 1219, 1049. Anal.
Calcd for C24H20N2OS2 (416.57): C, 69.20; H, 4.84; N, 6.72.
Found: C, 69.15; H, 4.62; N, 6.46.
Gen er a l P r oced u r e C: Iod in e-Lith iu m Exch a n ge of
6-Iod o-4-m eth oxy-2,2′-bip yr id in e (11). TMEDA (0.60 mL,
4.0 mmol) and, 15 min later, 6-iodo-4-methoxy-2,2′-bipyridine
(11, 0.31 g, 1.0 mmol) were added to a solution of BuLi (4.0
mmol) in hexane (1.6 mL) and Et2O (12 mL) at -70 °C. After
1 h at this temperature, the electrophile was added and
allowed to react as mentioned in the product description. The
solution was hydrolyzed with water (10 mL) and extracted with
CH2Cl2 (3 × 10 mL).
6-Deu ter io-4-m eth oxy-2,2′-bip yr id in e (19). The general
procedure C, using concd DCl (2 mL) in THF (5 mL) at -70
°C, gave 19 (eluent: Et2O): deuterium incorporation: 86%;29
mp 70 °C; 1H NMR (CDCl3) δ 4.04 (s, 3H), 6.85 (d, 1H, J ) 2.6
Hz), 7.32 (ddd, 1H, J ) 7.6, 4.9, 1.2 Hz), 7.81 (td, 1H, J ) 7.8,
1.9 Hz), 7.94 (d, 1H, J ) 2.6 Hz), 8.36 (dd, 1H, J ) 8.0, 2.1
Hz), 8.67 (dd, 1H, J ) 4.8, 1.8 Hz); IR (KBr) 1599, 1583, 1559,
1465, 1410, 1303, 1214, 1095, 1031.
6-Iod o-2,2′-bip yr id in e N-Oxid e (14). The general proce-
dure B, using a solution of iodine in THF (25 mL) at -70 °C
with stirring for 1 h, gave 55% of 14 (eluent: Et2O). Before
extraction, the solution was treated with Na2S2O3 until bleach-
1
ing; mp 134 °C; H NMR (CDCl3) δ 7.00 (t, 1H, J ) 8.0 Hz),
7.31 (ddd, 1H, J ) 7.5, 4.8, 0.9 Hz), 7.77 (td, 1H, J ) 7.8, 1.7
Hz), 7.89 (dd, 1H, J ) 8.0, 2.0 Hz), 8.10 (dd, 1H, J ) 8.0, 2.0
Hz), 8.67 (dd, 1H, J ) 4.8, 1.7 Hz), 8.79 (d, 1H, J ) 8.0 Hz);
IR (KBr) 1579, 1456, 1428, 1365, 1254, 1212. Anal. Calcd
for C10H7IN2O (298.08): C, 40.29; H, 2.37; N, 9.40. Found:
C, 40.56; H, 2.30; N, 9.16.
6-Br om o-4-n itr o-2,2′-bip yr id in e N-Oxid e (15). A solu-
tion of 6-bromo-2,2′-bipyridine N-oxide (13, 0.50 g, 2.0 mmol)
and KNO3 (4 g) in concentrated H2SO4 (10 mL) was heated
for 20 h at 80 °C. The mixture was neutralized with (NH4)2CO3
until compound 15 precipitates. Filtration and recrystalliza-
tion from CH2Cl2 gave 66% of 15: mp 171 °C; 1H NMR (CDCl3)
δ 7.45 (ddd, 1H, J ) 7.7, 4.7, 1.2 Hz), 7.88 (td, 1H, J ) 7.7, 1.9
Hz), 8.53 (d, 1H, J ) 3.2 Hz), 8.79 (dd, 1H, J ) 4.7, 1.9 Hz),
8.85 (dd, 1H, J ) 7.7, 1.2 Hz), 9.11 (d, 1H, J ) 3.2 Hz); IR
(KBr) 1558, 1450, 1388, 1343, 1272, 1155. Anal. Calcd for
4-Meth oxy-(2,2′-bip yr id in e)-6-ca r boxa ld eh yd e (Ca er u -
lom ycin E) (1). The general procedure C, using HCO2Et (0.32
mL, 4.0 mmol) in Et2O (5 mL) at -70 °C with stirring for 1 h,
gave 55% of 1 (eluent: Et2O): mp 80 °C (lit.1 83 °C); 1H NMR
(CDCl3) δ 4.01 (s, 3H, OCH3), 7.37 (dd, 1H, J ) 7.9, 4.8 Hz,
H5′), 7.49 (d, 1H, J ) 2.5 Hz, H5), 7.87 (td, 1H, J ) 7.9, 1.7
Hz, H4′), 8.19 (d, 1H, J ) 2.5 Hz, H3), 8.54 (dd, 1H, J ) 7.9,
1.2 Hz, H3′), 8.70 (dd, 1H, J ) 4.8, 1.7 Hz, H6′), 10.13 (s, 1H,
CHO); 13C NMR (CDCl3) δ 55.6, 107.4, 110.2, 121.2, 124.2,
136.8, 148.0, 153.9, 155.0, 158.1, 167.3, 193.3; IR (KBr) 3900,
2360, 1582, 1558, 1420, 1345, 1214, 1046, 749, 739, 692. Anal.
Calcd for C12H10N2O2 (214.22): C, 67.28; H, 4.70; N, 13.08.
Found: C, 67.05; H, 4.62; N, 13.34. The spectral character-
istics of compound 1 are in agreement with those already
described for the natural caerulomycin E.1 F r om 17.
A
solution of 4-methoxy-6-methyl-2,2′-bipyridine (17, 0.22 g, 1.1
mmol) and benzeneseleninic anhydride (0.79 g, 2.2 mmol) in
dioxane (15 mL) was refluxed for 24 h. Hydrolysis with 2 M
aqueous NaHCO3 (15 mL) and extraction with CH2Cl2 (3 ×
10 mL) gave 64% of 1 (eluent: Et2O). F r om 18. A solution
of 6-[bis(phenylthio)methyl]-4-methoxy-2,2′-bipyridine (18, 0.30
g, 0.73 mmol) in THF (3 mL) was added to a solution of
BF3‚Et2O (0.18 mL, 1.4 mmol) and HgO (0.30 g, 1.4 mmol) in
a THF/H2O 85:15 mixture (3 mL). The mixture was refluxed
for 1 h, poured onto a 2 M aqueous solution of K2CO3, and
extracted with CH2Cl2 (3 × 10 mL) to give 40% of 1 (eluent:
Et2O).
C
10H6BrN3O3 (296.08): C, 40.57; H, 2.04; N, 14.19. Found:
C, 40.50; H, 1.91; N, 14.07.
6-Iodo-4-n itr o-2,2′-bipyr idin e N-Oxide (16). From 6-iodo-
2,2′-bipyridine N-oxide (14), as previously described for the
1
synthesis of compound 15. Yield: 28%; mp 136 °C; H NMR
(CDCl3) δ 7.41 (dd, 1H, J ) 7.8, 4.7 Hz), 7.84 (td, 1H, J ) 7.8,
1.3 Hz), 8.66 (d, 1H, J ) 3.2 Hz), 8.74 (dd, 1H, J ) 4.7, 1.3
Hz), 8.74 (dd, 1H, J ) 7.8, 1.9 Hz), 9.04 (d, 1H, J ) 3.2 Hz);
IR (KBr) 1572, 1514, 1451, 1337, 1273, 1118. Anal. Calcd
for C10H6IN3O3 (343.08): C, 35.01; H, 1.76; N, 12.25. Found:
C, 34.98; H, 1.76; N, 12.24.

First Syntheses of Caerulomycin E and Collismycins A and C
J . Org. Chem., Vol. 63, No. 9, 1998 2897
(E )-4-Me t h oxy-(2,2′-b ip yr id in e )-6-ca r b oxa ld e h yd e
Oxim e (Ca er u lom ycin A) (2). A mixture of 4-methoxy-(2,2′-
bipyridine)-6-carboxaldehyde (1, 60 mg, 0.28 mmol), hydroxyl-
amine hydrochloride (0.10 g, 1.4 mmol), pyridine (0.10 mL, 1.2
mmol), and EtOH (2 mL) was refluxed for 45 min. The solvent
was evaporated under vacuum, and water (10 mL) was added.
Filtration of the precipitate and recrystallization from EtOH/
H2O 50:50 gave 75% of 2: mp 173 °C (lit.5 174-175 °C, lit.6
172-174 °C, lit.29 176-177 °C); 1H NMR (DMSO-d6) δ 3.91 (s,
3H, OCH3), 7.30 (d, 1H, J ) 2.4 Hz, H5), 7.44 (ddd, 1H, J )
7.2, 4.8, 1.3 Hz, H5′), 7.88 (d, 1H, J ) 2.4 Hz, H3), 7.92 (td,
1H, J ) 7.2, 1.6 Hz, H4′), 8.13 (s, 1H, CH), 8.36 (d, 1H, J )
7.2 Hz, H3′), 8.66 (d, 1H, J ) 4.8 Hz, H6′), 11.74 (s, 1H, OH);
13C NMR (DMSO-d6) δ 55.5, 105.5, 106.4, 120.7, 124.4, 137.2,
148.8, 149.2, 153.4, 154.5, 156.8, 166.5; IR (KBr) 2847, 2360,
1589, 1560, 1430, 1360, 1168, 1054, 981, 789, 741. Anal.
Calcd for C12H11N3O2 (229.24): C, 62.87; H, 4.84; N, 18.04.
Found: C, 63.11; H, 4.80; N, 17.84. The spectral character-
istics of compound 2 are in agreement with those already
described for the natural caerulomycin A.30
4-Meth oxy-5,6-bis(m eth ylth io)-2,2′-bipyr idin e (24). The
general procedure D was applied to 10. MeSSMe (0.90 mL,
10 mmol) was introduced at -70 °C, and the mixture was
allowed to reach rt after 5 min. The mixture was treated after
13 h at 25 °C to afford 44% of 24 (eluent: petroleum ether/
AcOEt 95:5): mp 100-101 °C; 1H NMR (CDCl3) δ 2.37 (s, 3H),
2.62 (s, 3H), 4.06 (s, 3H), 7.31 (ddd, 1H, J ) 7.4, 4.7, 1.1 Hz),
7.80 (td, 1H, J ) 7.8, 1.7 Hz), 7.81 (s, 1H), 8.48 (d, 1H, J ) 8.0
Hz), 8.64 (dd, 1H, J ) 4.6, 1.7 Hz); IR (KBr) 2919, 1540, 1449,
1430, 1359, 1259, 1209, 1046. Anal. Calcd for C13H14N2OS2
(278.40): C, 56.09; H, 5.07; N, 10.06. Found: C, 56.32; H, 5.21;
N, 9.94.
4-Meth oxy-5-(m eth ylth io)-(2,2′-bip yr id in e)-6-ca r boxa l-
d eh yd e (25). TMEDA (0.60 mL, 4.0 mmol) and, 15 min later,
6-bromo-4-methoxy-5-(methylthio)-2,2′-bipyridine (23, 0.31 g,
1.0 mmol) were added to a solution of BuLi (4.0 mmol) in
hexane (1.6 mL) and Et2O (12 mL) at -70 °C. After 30 min
at this temperature, DMF (0.31 mL, 4.0 mmol) in Et2O (5 mL)
was added at -70 °C, and the temperature was allowed to
reach -30 °C. After 45 min, addition of water (10 mL) and
extraction with CH2Cl2 (3 × 10 mL) gave 55% of 25 (eluent:
Gen er a l P r oced u r e D: Meta la tion of 6-Ch lor o- a n d
6-Br om o-4-m eth oxy-2,2′-bip yr id in es (6, 10). BuLi (4.0
mmol) in hexane (1.6 mL) was added to a solution of diiso-
propylamine (0.56 mL, 4.0 mmol) in THF (5 mL) at 0 °C. The
6-substituted-4-methoxy-2,2′-bipyridine (1.0 mmol) was intro-
duced at -70 °C. After 1 h at this temperature, the electro-
phile was added and allowed to react as mentioned in the
product description. The solution was hydrolyzed with water
(10 mL) and extracted with CH2Cl2 (3 × 10 mL).
1
petroleum ether/AcOEt 80:20): mp 145 °C; H NMR (CDCl3)
δ 2.51 (s, 3H), 4.17 (s, 3H), 7.38 (ddd, 1H, J ) 7.6, 4.8, 1.0
Hz), 7.87 (ddd, 1H, J ) 7.9, 7.6, 1.7 Hz), 8.19 (s, 1H), 8.60 (dd,
1H, J ) 7.9, 1.0 Hz), 8.69 (dd, 1H, J ) 4.8, 1.7 Hz), 10.64 (s,
1H); IR (KBr) 2926, 1703, 1570, 1533, 1421, 1368, 1331, 1217,
1050. Anal. Calcd for C13H12N2O2S (260.32): C, 59.98; H, 4.65;
N, 10.76. Found: C, 60.28; H, 4.37; N, 10.51.
(E)-4-Met h oxy-5-(m et h ylt h io)-(2,2′-b ip yr id in e)-6-ca r -
boxa ld eh yd e Oxim e (Collism ycin A) (3). The procedure
described for the synthesis of compound 2 was applied to
4-methoxy-5-(methylthio)-(2,2′-bipyridine)-6-carboxaldehyde (25).
Yield: 71%; mp 173-174 °C (lit.7 174-176 °C, lit.8 170-172
°C); 1H NMR (CDCl3) δ 2.39 (s, 3H, SCH3), 4.13 (s, 3H, OCH3),
7.35 (ddd, 1H, J ) 7.5, 4.8, 1.0 Hz, H5′), 7.87 (ddd, 1H, J )
7.9, 7.5, 1.7 Hz, H4′), 8.05 (s, 1H, H3), 8.55 (dd, 1H, J ) 7.9,
1.0 Hz, H3′), 8.68 (dd, 1H, J ) 4.8, 1.7 Hz, H6′), 9.11 (s, 1H,
CH), 10.2 (s, 1H, OH); 13C NMR (CDCl3) δ 18.5, 56.4, 103.7,
121.9, 122.1, 124.3, 137.2, 147.5, 148.9, 152.6, 155.1, 157.4,
167.4; IR (KBr) 3359, 2934, 1580, 1566, 1551, 1458, 1429, 1370,
1283, 1250, 1215, 1044, 916, 862, 793, 747. Anal. Calcd for
6-Ch lor o-5-deu ter io-4-m eth oxy-2,2′-bipyr idin e (20). The
general procedure D starting from 6 and using concd DCl (2
mL) in THF (5 mL) at -70 °C gave 20 (eluent: CH2Cl2):
deuterium incorporation: 75%;29 1H NMR (CDCl3) δ 3.95 (s,
3H), 7.33 (ddd, 1H, J ) 7.6, 4.5, 1.6 Hz), 7.79 (td, 1H, J ) 7.6,
1.8 Hz), 7.85 (s, 1H), 8.40 (dd, 1H, J ) 7.6, 1.6 Hz), 8.66 (dd,
1H, J ) 4.5, 1.8 Hz).
6-Br om o-5-deu ter io-4-m eth oxy-2,2′-bipyr idin e (21). The
general procedure D was applied to 10 as described for 20;
deuterium incorporation: 80%;29 1H NMR (CDCl3) δ 3.94 (s,
3H), 7.33 (ddd, 1H, J ) 7.6, 4.7, 1.0 Hz), 7.81 (ddd, 1H, J )
7.9, 7.6, 1.7 Hz), 7.96 (s, 1H), 8.40 (dd, 1H, J ) 7.9, 1.0 Hz),
8.66 (dd, 1H, J ) 4.7, 1.7 Hz).
C
13H13N3O2S (275.33): C, 56.71; H, 4.76; N, 15.26. Found: C,
6-Ch lor o-4-m eth oxy-5-(m eth ylth io)-2,2′-bipyr idin e (22).
The general procedure D was applied to 6. Methyl disulfide
(MeSSMe, 0.36 mL, 4.0 mmol) was introduced at -70 °C, and
the mixture was allowed to reach rt after 30 min, before
immediate treatment to afford 98% of 22 (eluent: petroleum
57.00; H, 5.02; N, 14.98. The spectral characteristics of
compound 3 are in agreement with those already described
for the natural collismycin A.7,8
4-Met h oxy-5-(m et h ylt h io)-(2,2′-b ip yr id in e)-6-m et h a -
n ol (Collism ycin C) (4). NaBH4 (15 mg, 0.40 mmol) was
added to a solution of 4-methoxy-5-(methylthio)-(2,2′-bipyri-
dine)-6-carboxaldehyde (25, 25 mg, 0.10 mmol) in EtOH (6
mL). After 15 min, a 1 M aqueous solution of HCl (10 mL)
was added. Neutralization with K2CO3 and extraction with
CH2Cl2 (3 × 10 mL) gave 96% of 4 (eluent: CHCl3/MeOH 99.5:
1
ether/AcOEt 90:10): mp 104 °C; H NMR (CDCl3) δ 2.44 (s,
3H), 4.08 (s, 3H), 7.31 (dd, 1H, J ) 7.5, 4.7 Hz), 7.79 (dt, 1H,
J ) 7.7, 1.8 Hz), 7.96 (s, 1H), 8.39 (d, 1H, J ) 7.9 Hz), 8.63
(ddd, 1H, J ) 4.7, 1.8, 0.9 Hz); 13C NMR (CDCl3) δ 17.6, 56.6,
102.6, 120.4, 121.3, 124.2, 136.8, 148.9, 154.0, 154.5, 156.0,
168.0. Anal. Calcd for C12H11ClN2OS (266.74): C, 54.03; H,
4.16; N, 10.50. Found: C, 54.31; H, 4.22; N, 10.25.
1
0.5): mp 113-114 °C (lit.7 104-106 °C); H NMR (CDCl3) δ
6-Br om o-4-m eth oxy-5-(m eth ylth io)-2,2′-bipyr idin e (23).
The general procedure D was applied to 10. MeSSMe (0.90
mL, 10 mmol) was introduced at -70 °C, and the mixture was
allowed to reach rt after 5 min, before immediate treatment
to afford 61% of 23 (eluent: petroleum ether/AcOEt 90:10):
mp 124.5 °C; 1H NMR (CDCl3) δ 2.49 (s, 3H), 4.13 (s, 3H), 7.36
(ddd, 1H, J ) 7.5, 4.8, 1.2 Hz), 7.85 (ddd, 1H, J ) 8.0, 7.5, 1.7
Hz), 8.02 (s, 1H), 8.45 (dd, 1H, J ) 8.0, 1.2 Hz), 8.68 (dd, 1H,
J ) 4.8, 1.7 Hz); IR (KBr) 2920, 1560, 1522, 1449, 1414, 1360,
1252, 1210, 1033. Anal. Calcd for C12H11BrN2OS (311.20): C,
46.31; H, 3.56; N, 9.00. Found: C, 46.32; H, 3.51; N, 9.04.
2.38 (s, 3H, SCH3), 4.14 (s, 3H, OCH3), 4.81 (t, 1H, J ) 4.1
Hz, OH), 4.96 (d, 2H, J ) 4.1 Hz, CH2), 7.37 (ddd, 1H, J )
7.5, 4.8, 1.2 Hz, H5′), 7.86 (ddd, 1H, J ) 7.9, 7.5, 1.8 Hz, H4′),
8.03 (s, 1H, H3), 8.46 (ddd, 1H, J ) 7.9, 1.2, 0.9 Hz, H3′), 8.70
(ddd, 1H, J ) 4.8, 1.8, 0.9 Hz, H6′); 13C NMR (CDCl3) δ 17.4,
56.3, 62.4, 102.7, 117.5, 121.1, 124.2, 137.0, 149.1, 154.9, 155.4,
160.3, 167.2; IR (KBr) 3361, 2923, 1577, 1561, 1550, 1458,
1427, 1366, 1246, 1214, 1041, 916, 862, 793, 745. Anal. Calcd
for
C13H14N2O2S (262.33): C, 59.59; H, 5.38; N, 10.68.
Found: C, 59.61; H, 5.34; N, 10.59. The spectral character-
istics of compound 4 are in agreement with those already
described for the natural collismycin C.7
(30) McInnes, A. G.; Smith, D. G.; Wright, J . L. C.; Vining, L. C.
Can. J . Chem. 1977, 55, 4159.
J O972022I