3810
D. Pandey et al. / Bioorg. Med. Chem. 12 (2004) 3807–3813
1
uncorrected. The C, H, N analyses were carried out on
CARLO-ERBA EA1108 elemental analyser. Thin-layer
chromatography (TLC) was performed on readymade
silica gel plates (Merck) by means of solvent systems
indicated below. Column chromatography separations
were obtained on Silica gel (230–400 mesh).
Compound 4a: Yield 65%, H NMR (300 MHz,
CDCl ): d 1.38 (m, 3H) 2-Me, 2.07 (m, 1H) C –H, 1.27
(m, 3H) 4-Me, 3.51 (d, 1H) C –H, 1.33 (s, 3H) 6-Me,
3
4
5
1.56 (dd, 1H) and 1.90–1.96 (m, 1H) C
–H, 1.08 (m, 3H) 8-Me, 3.01 (m, 1H) C10–H, 1.13 (m,
3H) 10-Me, 1.47 (s, 3H) 12-Me, 1.50 (m, 1H) and 1.90–
7
–H, 2.58 (m, 1H)
C
8
1
C
6
1
3
3
.96 (m, 1H) C14–H, 0.85 (t, 3H) CH
0
3
CH
–H, 2.74 (m, 1H) C
2
, 4.38 (d, 1H)
0
0
1
–H, 3.24 (m, 1H) C
0
2
3
–H, 2.28 (s,
H) C –NMe , 1.20–1.28 (m, 1H) C –H, 3.50–3.58 (m,
0
3
2
4
5
.1. Erythromycin-9-oxime 3
0
0
00
00
H) C
.04 (dd, 1H) 4 H, 4.04 (m, 1H) 5 H, 1.25 (s, 1H) 7 H,
5
–H, 1.26 (m, 3H) C
5
–Me, 4.99 (dd, 1H) 1 H,
00
00
Erythromycin (0.730 g, 1 mM) was taken in pyridine
5 mL) and hydroxylamine hydrochloride (10 mM) was
00
.32(s, 3H) 3 -OCH , 7.20 (s, 5H) C H , 5.05 (s, 2H)
5
3
6
(
13
PhCH2 3.94 (s, 2H) NH–CH2; C NMR (50 MHz,
CDCl ): d 176.4 (C-1), 46 (C-2), 16.5 (C –Me), 79.2(C-
), 35.9 (C-4), 9.8 (C–4Me), 83.5 (C-5), 78.0 (C-6), 27.5
added to this solution. The reaction mixture was stirred
at room temperature for 72h. Pyridine was evaporated
under reduced pressure and the residue was taken in
3
2
3
(
(
1
1
C–6Me), 37.2(C-7), 45.5 (C-8), 19.2(C–8Me), 168.2
C-9), 38.9 (C-10),12.3 (C–10Me), 68.9 (C-11), 73.8 (C-
2 2
CH Cl . The organic layer was washed with brine and
dried over sodium sulfate. Solvent was removed under
reduced pressure and the residue was precipitated by
addition of hexane. The compound isolated white
2), 17.1 (C–12Me), 75 (C-13), 21.5 (C-14), 12.4 (C-15),
0
0
0
0
04 (C-1 ), 72.3 (C-2 ), 65.1 (C-3 ), 40.2(C–3 NMe ),
2
0
0
0
00
1
29.3 (C-4 ), 68.9 (C-5 ), 23.2 (C–5 Me), 96.5 (C-1 ),
00
amorphous solid. Yield 0.7 g, mp 157–164 ꢁC; H NMR
00
3
5.1(C-2 ), 78.0 (C-4 ), 128.7–128.9 (5C of C
1C of C H ), 68.6 (PhCH ), 157.2(CO–NH), 46.2
6 5
H ), 137.4
(
2
1
300 MHz, CDCl
-Me, 3.50–3.58 (m, 1H) C –H, 2.07 (dq, 1H) C
3 4
3
): d 2.66 (m, 1H) C
2
–H, 1.38 (m, 3H)
–H,
.27 (m, 3H) 4-Me, 3.51 (d, 1H) C –H, 1.33 (s, 3H) 6-
(
(
6
5
2
þ
NHCH
2
), 170.8 (CH
2
CO); Mass (FAB) 940 (M + H) .
5
Me, 1.56 (dd, 1H) and 1.90–1.96 (m, 1H) C
H) C –H, 1.08 (m, 3H) 8-Me, 3.01 (m, 1H) C10–H, 1.13
m, 3H) 10-Me, 3.86 (d, 1H) C11–H, 1.47 (s, 3H) 12-Me,
7
–H, 2.58 (m,
1
Compound 4b: Yield 51.2%, H NMR (200 MHz,
CDCl ): d 1.38 (m, 3H) 2-Me, 2.07 (m, 1H) C –H, 1.27
1
(
8
3
4
(m, 3H) 4-Me, 3.51 (d, 1H) C –H, 1.33 (s, 3H) 6-Me,
1.56 (dd, 1H) and 1.90–1.96 (m, 1H) C –H, 2.58 (m, 1H)
C –H, 1.08 (m, 3H) 8-Me, 3.01 (m, 1H) C –H, 1.13 (m,
8
3H) 10-Me, 1.47 (s, 3H) 12-Me, 1.49 (m, 1H) and 1.90–
5
5
1
3
.18 (dd, 1H) C –H, 1.49 (m, 1H) and 1.90–1.96 (m,
13
0
7
H) C14–H, 0.85 (t, 3H) CH
0
3
CH
–H, 2.74 (m, 1H) C
2
, 4.38 (d, 1H) C
0
1
–H,
–H, 2.28 (s, 6H)
10
.24 (dd, 1H) C
0
2
3
0
C –NMe , 1.20–1.28 (m, 1H) C –H, 3.50–3.58 (m, 1H)
2
C
3
4
0
0
00
1.96 (m, 1H) C –H, 0.85 (t, 3H) CH CH , 4.38 (d, 1H)
14
3
2
5
–H, 1.26 (m, 3H) C
5
–Me, 4.98 (dd, 1H) 1 H, 1.59
0 0
C –H, 3.24 (m, 1H) C –H, 2.74 (m, 1H) C –H, 2.28 (s,
1 2
0
00 00 00
3
(
dd, 1H) 2 Hax, 2.38 (dd, 1H) 2H eq, 3.04 (dd, 1H) 4 H,
0 0
3 2 4
6H) C –NMe , 1.20–1.28 (m, 1H) C –H, 3.50–3.58 (m,
00 00 00
.04 (dq, 1H) 5 H, 1.31 (d, 1H) 6 H, 1.25 (s, 1H) 7 H,
4
3
4
4
4
0
0
0
0
00
13
1H) C –H, 1.26 (m, 3H) C –Me, 4.98 (dd, 1H) 1 H,
5 5
.32(s, 3H) 3 -OCH
6 (C-2), 16.5 (C –Me), 79.2(C-3), 35.9 (C-4), 9.8 (C–
Me), 83.5 (C-5), 78.0 (C-6), 27.5 (C–6Me), 37.2 (C-7),
5.5 (C-8), 19.2(C–8Me), 168.2(C-9), 38.9 (C-10), 1 2. 3
3 3
; C NMR (CDCl ): d 176.5 (C-1),
00 00 00
.04 (dd, 1H) 4 H, 4.04 (m, 1H) 5 H, 1.25 (s, 1H) 7 H,
3
3
C
2
0
0
.32(s, 3H) 3 -OCH , 6.88 (d, 2H) and 7.96 (d, 2H)
3
þ
6
H
4
, 3.83 (s, 3H) OCH
3
; Mass (FAB) 883 (M + H) .
15C 61.20%, H 8.45%, N 3.17%.
Anal. Calcd C45
Found: C 61.28%, H 8.49%, 3.37N%.
H
74
N
2
O
(
(
6
2
(
C-10Me), 68.9 (C-11), 73.8 (C-12), 17.1 (C-12Me), 75
0
0
C-13), 21.5 (C-14), 12.4 (C-15), 104 (C-1 ), 72.3 (C-2 ),
0 0 0 0
5.1 (C-3 ), 40.2(C-3 NMe ), 29.3 (C-4 ), 68.9 (C-5 ),
2
1
0
00
00
00
Compound 4c: Yield 70%, H NMR (200 MHz, CDCl ):
3
d 1.38 (m, 3H) 2-Me, 2.07 (m, 1H) C –H, 1.27 (m, 3H) 4-
3.2 (C–5 Me), 96.5 (C-1 ), 35.1 (C-2 ), 72.3 (C-3 ), 78.0
0
0
þ
4
C-4 ); Mass (FAB) 749 (M + H) .
Me, 3.51 (d, 1H) C
and 1.90–1.96 (m, 1H) C
m, 3H) 8-Me, 3.01 (m, 1H) C –H, 1.13 (m, 3H) 10-Me,
5
–H, 1.33 (s, 3H) 6-Me, 1.56 (dd, 1H)
7
–H, 2.58 (m, 1H) C –H, 1.08
8
(
10
5
.2. Erythromycin-9-oxime esters 4(a–d)
1.47 (s, 3H) 12-Me, 1.49 (m, 1H) and 1.90–1.96 (m, 1H)
0
C
(m, 1H) C
14–H, 0.85 (t, 3H) CH
0
3
CH
–H, 2.74 (m, 1H) C
2
, 4.38 (d, 1H) C
0
1
–H, 3.24
0
0
General procedure for all the compounds: To a solution
of erythromycin-9-oxime 200 mg (0.25 mM) in 10 mL
dichloromethane was added the carboxylic acid,
2
3
–H, 2.28 (s, 6H) C
–H, 3.50–3.58 (m, 1H) C
3
–
–
0
NMe , 1.20–1.28 (m, 1H) C
0
H, 1.26 (m, 3H) C
2
4
5
00
5
–Me, 4.98 (dd, 1H) 1 H, 3.04 (dd,
1H) 4 H, 4.04 (m, 1H) 5 H, 1.25 (s, 1H) 7 H, 3.32(s,
3H) 3 -OCH 0.88 (s, 9H) Me C, 1.45 (d, 3H) CH –CH;
00 00 00
(
0.25 mM). The reaction mixture was cooled at 0 ꢁC then
0
0
dicyclohexylcarbodiimide (60 mg, 0.25 mM) is added
under stirring and stirred for additional 3 h at room
temperature. Dicyclohexylurea was removed by filtra-
tion and the filtrate was evaporated to dryness in vacuo.
The residue was taken in ethyl acetate and washed with
3
3
3
þ
Mass (ESMS) 921 (M + H) . Anal. Calcd C45
O
8.98%, N 4.58%.
H
16C 58.74%, H 8.87%, N 4.57%. Found: C 58.22%, H
81 3
N
1
5
% NaHCO
3
and brine, dried on anhydrous MgSO
4
Compound 4d: Yield 53.1%, H NMR (200 MHz,
CDCl ): d 1.38 (m, 3H) 2-Me, 2.07 (m, 1H) C –H, 1.27
evaporated under reduced pressure and precipitated
through hexane. To remove the traces of DCU the
resulting compound was treated with cold tetrahydro-
furan and the solid separated by filtration. The filtrate
was evaporated under reduced pressure to obtain the
title compound as white solid. Yield (52–70%).
3
4
(m, 3H) 4-Me, 3.51 (d, 1H) C
–H, 1.33 (s, 3H) 6-Me,
5
1.56 (dd, 1H) and 1.90–1.96 (m, 1H) C
–H, 1.08 (m, 3H) 8-Me, 3.01 (m, 1H) C10–H, 1.13 (m,
3H) 10-Me, 1.47 (s, 3H) 12-Me, 1.49 (m, 1H) and 1.90–
1.97 (m, 1H) C14–H, 0.85 (t, 3H) CH CH , 4.38 (d, 1H)
7
–H, 2.58 (m, 1H)
C
8
3
2