Baylis-Hillman protocol in an enantiocontrolled synthesis of pentenomycin I

Article abstract of DOI:10.1055/s-1999-2650

A new route to the cyclopentanoid antibiotic (-)-pentenomycin 11 has been developed by application of the Baylis-Hillman reaction on the chiral cyclopentadienone synthon.

Full text of DOI:10.1055/s-1999-2650

LETTER
419
Baylis-Hillman Protocol in an Enantiocontrolled Synthesis of Pentenomycin I
Tsutomu Sugahara, Kunio Ogasawara*
Pharmaceutical Institute, Tohoku University, Aobayama, Sendai 980-8578, Japan
Fax +81-22-217-6845; E-mail: konol@mail.cc.tohoku.ac.jp
Received 4 February 1999
Abstract: A new route to the cyclopentanoid antibiotic (–)-pen-
tenomycin I 1 has been developed by application of the Baylis-Hill-
man reaction on the chiral cyclopentadienone synthon.
Key words: pentenomycin I; enantiocontrolled synthesis; chiral
building block; Baylis-Hillman reaction; chiral cyclopentadienone
Scheme 1
(
–)-Pentenomycin I 1 was isolated from the culture filtrate
Since we have established own procedures for the con-
of Streptomyces eurythermus and reported to show mod-
erate activity against Gram-positive and Gram-negative
bacteria. Despite its rather simple structure, its synthesis
is not an easy task owing to its sensitivity towards acids
and bases. So far there have been four racemic and two
chiral syntheses reported. In this paper, we wish to re-
port an enantio- and diastereocontrolled synthesis of (–)-
pentenomycin
struction of ketodicyclopentadiene (KDP) 2 in both enan-
4
6
tiomeric forms, we chose the Baylis-Hillman reaction to
install the hydroxymethyl functionality on the appropriate
1
2
sp carbon center. Thus, KDP (+)-2 was stirred with 3
2
equivalents of formalin in THF in the presence of 4-(N,N-
2
c,3
7
dimethylamino)pyridine (DMAP) (15 mol %) at room
temperature. Although the reaction was sluggish and did
I
1
starting
from
chiral
not complete within 3.5 days, the desired a-hydroxymeth-
4
ketodicyclopentadiene (KDP) (+)-2 which we used as the
28
ylenone 3, [a] +78 (c 0.93, CHCl ), was obtained in 67%
synthetic equivalent of chiral cyclopentadienone5
D
3
yield after separation of the unchanged starting KDP (+)-
(Scheme 1).
2
[84% yield based on the recovered (+)-2]. To discrimi-
nate the two olefin functionalities in the molecule, the
Scheme 2
Synlett 1999, No. 4, 419–420 ISSN 0936-5214 © Thieme Stuttgart · New York

4
20
T. Sugahara, K. Ogasawara
LETTER
product was first transformed into the endo-allyl alcohol In summary, we have accomplished an enantiocontrolled
2
6
4
, [a]D –91 (c 1.19, MeOH), in 97% yield, by convex synthesis of (–)-pentenomycin I 1 from chiral KDP (+)-2
face selective reduction with diisobutylaluminum hydride employing the Baylis-Hillman reaction as the key step.
DIBAL). Then, the alcohol 4 was exposed to N-bromo-
(
succinimide to block one of the olefins regioselectively by
quantitative generation of the single bromo-ether 5,
Acknowledgement
8
2
6
[
a]D –103.3 (c 1.06, CHCl ), whose primary hydroxy We thank Discovery Research Laboratory, Tanabe Seiyaku Co.,
3
Ltd., for helpful information.
functionality was protected by a methoxymethyl (MOM)
group to give the MOM ether 6, [a]D2 –69.8 (c 1.44,
7
CHCl ), in 87% overall yield. This was dihydroxylated,
stereoselectively, from the convex face to give the exo-
3
References and Notes
8
2
6
(1) a) Umino, K.; Furumai, T.; Matsuzawa, N.; Awataguchi, Y.;
Ito, T.; Okuda, T. J. Antibiot. 1973, 26, 506. b) Umino, K.; Ta-
keda, N.; Ito, Y.; Okuda, T. Chem. Pharm. Bull. 1974, 22,
diol 7, [a]D –54.2 (c 1.35, CHCl ), which was then trans-
3
2
5
formed into the acetonide 8, [a]D –60 (c 1.05, CHCl ), in
3
8
6% overall yield. Treatment of 8 with zinc in warm
1233. c) Date, T.; Aoe, K.; Kotera, K.; Umino, K. Chem.
methanol containing 10% of acetic acid regenerated the
Pharm. Bull . 1974, 22, 1963.
olefin functionality to furnish the secondary alcohol 9,
(2) a) Smith, III, A. B.; Branca, S. J.; Pilla, N. N.; Guaciaro, M.
A. J. Org. Chem. 1982, 47, 1855. b) Verlaak, J. M. J.; Klunder,
A. J. H.; Zwanenburg, B. Tetrahedron Lett. 1982, 23, 5463.
c) Hetmanski, M.; Purcell, N.; Stoodley, R. J. J. Chem. Soc.,
Perkin Trans. 1 1984, 2089. d) Pohmakotr, M.; Popuang, S.
Tetrahedron Lett. 1991, 32, 275.
2
5
[
a]D –11.4 (c 1.01, CHCl ), mp 80-82 °C, which was ox-
3
idized with pyridinium dichromate (PDC) to give the ke-
tone 10, [a]D +150.2 (c 1.36, CHCl ), in 88% overall
2
3
3
yield. This ketone may be taken as the triply protected
form of pentenomycin I 1 whose enone double bond was
first regenerated on thermolysis in diphenyl ether at 280
(
3) Verheyden, J. P. H.; Richardson, A. C.; Bhatt, R. S.; Grant, B.
D.; Fitch, W. L.; Moffatt, J. G. Pure Appl. Chem. 1978, 50,
1363.
°
C for 20 min to give the doubly protected pentenomycin
2
6
I 11, [a]D +26 (c 0.93, CHCl ), in 93% yield. The optical
(4) A pertinent synthesis: Sugahara, T.; Kuroyanagi, Y.; Ogasa-
3
wara, K. Synthesis 1996, 1101.
purity of 11 was determined as > 99% ee by hplc using a
chiral column (CHIRALCEL OJ, elution with 5% iPrOH-
hexane). Finally, this was stirred in 90% trifluoroacetic
(5) a) Ogasawara, K. Pure Appl. Chem. 1994, 66, 2119. b) Ogasa-
wara, K. J. Syn. Org. Chem. Jpn. 1996, 54, 15.
(
6) Pertinent reviews, see: a) Drewes, S. E.; Roos, G. H. P. Tetra-
hedron 1988, 44, 4653. b) Basavaiah, D.; Rao, P. D.; Hyma,
R. S. Tetrahedron 1996, 52, 8001.
2
d,3
acid
at 0 °C for 24 h to remove the two protecting
9
28
groups to give natural pentenomycin I 1, [a] –32.6 (c
D
1
b
21
0
.34, EtOH) (natural : [a] –32 (c 0.3, EtOH)), in 62%
(7) Rezgni, F.; Elgaied, M. M. Tetrahedron Lett. 1998, 39, 5965.
D
(
(
8) Takano, S; Inomata, K.; Ogasawara, K. Chem. Lett. 1989, 359.
yield (Scheme 2).
2
9
9) Triacetate, mp 111-112 °C; [a] –8.6 (c 0.19, EtOH) [lit.:
D
2
1
1b
mp 111-112 °C; [a] –24 (c 0.36, EtOH) ; mp 112-114 °C;
D
2
c
[
a] –8 (c 0.5, EtOH) ].
D
Synlett 1999, No. 4, 419–420 ISSN 0936-5214 © Thieme Stuttgart · New York