Chemistry Reference
In-Depth Information
drying, the dichloromethane was evaporated to give 10.52 g (84.8% yield) of a
clear liquid, which could be further purified by vacuum distillation; bp 44
C/
0.001 mmHg.
FR-900482 918,amitomycin-like antitumor agent, isolated from Streptomyces
sandaensis, exists as a 2:1 mixture (b:a ether bridge) of stereoisomers at neutral pH,
but almost exclusively as the b-isomer in acidic media. An asymmetric route to its
core nucleus involves the cyclization of an aziridinyl radical derived from 914 to
give a functionalized indole nucleus 915
916. In a further step, a benzyloxy-
carbonyl group is introduced on the primary alcohol function using CDI and benzyl
alcohol, affording 917 in 71% yield [659].
!
O
914
917
O
O
O
Bn
OBn
OBn
OTBDMS
71 %
NH
2
OH
O
CHO
OH
H
NH
O
MeO
2
C
MeO
2
C
N
N
OHC
N
NBoc
Br
918
2. BnOH
DMAP
63°C, 3 h
N
1.
CDI
MeCN
3.5 h
Bu
3
SnH
Boc
toluene
OH
OBn
OBn
OTBDMS
CHO
H
H
MeO
2
C
MeO
2
C
N
N
NBoc
NBoc
916
915
Typical procedure. Methyl (1aS,8R,8aS,8bR)-1,1a,2,8,8a,8b-hexahydro-7-benzyloxy-
8-(benzyloxycarbonyl)oxymethyl-1-tert-butyloxycarbonyl-8-formylazirino[2
0
,3
0
:3,4] pyrrolo-
[1,2a]indole-5-carboxylate 917 [659]: CDI (150 mg, 0.925 mmol) was added to a so-
lution of alcohol 916 (385 mg, 0.779 mmol) in acetonitrile (12 mL), and the reac-
tion mixture was stirred for 3.5 h. Benzyl alcohol (600
L, 5.80 mmol) and DMAP
(60.0 mg, 0.491 mmol) were added, and the reaction mixture was heated at 63
C
for 3.0 h. The solvent was then removed, and the residue was submitted to flash
chromatography (column prepared with dichloromethane; eluent: 10-25% EtOAc/
hexanes) to give a pale-yellow foam of 917 containing traces of an impurity (349
mg, 71%). This material was suitable for further experiments. A sample of 917 was
purified by radial chromatography (EtOAc/dichloromethane, 3:97) for character-
ization purposes; [a]
23
D
m
0.540, chloroform).
A cyclocarbonate moiety is formed on a macrolide scaffold during the synthesis
of an intermediate of erythromycin A derivatives. Erythromycin A is a safe and effec-
tive antibiotic for the treatment of Gram-positive pathogens, and, in particular, it is
the drug of choice for the treatment of Legionnaires'disease. Erythromycin A, how-
¼þ
36.0 (c
¼
