A new stereoselective route to (-)-octalactin A based on intramolecular SmI2 promoted Reformatsky reaction

Article abstract of DOI:10.1055/s-1998-1778

A novel stereoselective synthesis of the key left-hand fragment of (-)-octalactin A has been achieved from methyl (R)-3-hydroxy-2-methylpropionate employing SmI₂ promoted intramolecular Reformatsky reaction of a δ-(bromoacetoxy)aldehyde as a key step.

Full text of DOI:10.1055/s-1998-1778

July 1998
SYNLETT
735
A New Stereoselective Route to (–)-Octalactin A Based on Intramolecular SmI Promoted
2
Reformatsky Reaction
Susumu Inoue, Yoshiharu Iwabuchi, Hiroshi Irie, Susumi Hatakeyama*
Faculty of Pharmaceutical Sciences, Nagasaki University, Nagasaki 852-8131, JAPAN
Fax 81-95-848-4286
Received 31 March 1998
Abstract:A novel stereoselective synthesis of the key left-hand
fragment of (-)-octalactin A has been achieved from methyl (R)-3-
hydroxy-2-methylpropionate employing SmI promoted intramolecular
2
Reformatsky reaction of a δ-(bromoacetoxy)aldehyde as a key step.
Octalactin A (1) and octalactin B, a closely related congener, were
isolated from a marine actinomycete of the genus Streptomyces found
1
on the surface of a gorgonian octacoral. Octalactin A (1) displays
potent in vitro cytotoxicity against B-16-F10 murine melanoma and
1
HCT-116 human colon tumor cell lines. The unique structure
containing a characteristic eight-membered lactone moiety as well as
the above-mentioned intriguing biological activity has spurred much
2
2a
2b
research on the synthesis of octalactin A (1). Buszek and Clardy
have independently established an efficient convergent approach
involving coupling of a left-hand fragment 2 and a right-hand fragment
3. We describe herein a novel stereoselective synthesis of the key left-
hand fragment 2 (R = TBS), which constitutes a formal synthesis of
natural (–)-octalactin A (1).
18
CHCl ), and (3R)-hydroxylactone 13, [α]
–23.7 (c 0.54, CHCl ), in
3
3
D
63% yield. The poor diastereoselectivity of this SmI promoted reaction
2
was not problematic, however, because the undesired isomer 12 could
be converted to the desired isomer 13 almost quantitatively by
8,9
10
sequential Dess-Martin oxidation and NaBH reduction. Protection
4
of 13 as its tert-butyldimethylsilyl ether followed by hydrogenolytic
removal of the benzyl ether protecting group afforded alcohol 14,
The strategy we have employed to construct the eight-membered
18
11
20
lactone structure of 2 relies upon SmI promoted intramolecular
2
[α]
–61.9 (c 0.32, CHCl ) {antipode:
[α]
D
+56.3 (c 1.05,
D
3
3
Reformatsky reaction of an δ-(bromoacetoxy)aldehyde which follows
CHCl )}, in 73% yield. Finally, Dess-Martin oxidation of 14 furnished
3
4
22
the Inanaga’s protocol.
the key left-hand fragment 2 (R = TBS), [α]
{antipode: [α]
2 (R = TBS) exhibited identical spectral properties ( H and C NMR,
–94.0 (c 1.08, CHCl )
3
D
11
24
+87.2 (c 1.02, CHCl )}, in 95% yield. Both 14 and
3
The required δ-(bromoacetoxy)aldehyde 11 was prepared as shown in
Scheme 1. Commercially available methyl (R)-3-hydroxy-2-
methylpropionate (4) was first subjected to a conventional nine-step
D
1
13
IR, HRMS) with those of their antipodes synthesized by Clardy and
2b
5
McWilliams. Since the antipode of 2 (R = TBS) has already been
straightforward chain-elongation to give (E)-allylic alcohol 7 in 52%
2b
6
converted to (+)-octalactin A by Clardy and McWilliams, the present
overall yield. Katsuki-Sharpless catalytic asymmetric epoxidation of 7
work provides a new route to natural (–)-octalactin A.
gave epoxide 8 which, upon nucleophilic opening with methyllithium in
the presence of a catalytic amount of CuCN followed by NaIO
4
7
oxidation, gave diol 9 in 52% yield. Selective monobenzylation of 9
followed by bromoacetylation of the resulting secondary alcohol
afforded bromoacetate 10 in 74% yield. Upon sequential acidic
methanolysis and Swern oxidation, 10 gave δ-(bromoacetoxy)aldehyde
11 in 97% yield.
Acknowledgment. We gratefully thank Professor Jon Clardy (Cornell
University) for providing us with spectral data and specific rotations of
the antipode of 14 and 2 (R = TBS).
References and Notes
The crucial SmI promoted cyclization of 11 was carried out according
2
4
(1) Tapiolas, D. M.; Roman, M.; Fenical, W.; Stout, T. J.; Clardy, J. J.
Am. Chem. Soc. 1991, 113, 4682.
to the procedure reported by Inanaga and co-workers. Thus, treatment
–3
–3
of a diluted THF solution of 11 (2 x 10 mol·dm ) with SmI at 0 °C
2
allowed intramolecular Reformatsky type of reaction to provide a 2:1
(2) (a) Buszek, K. R.; Sato, N.; Jeong, Y. J. Am. Chem. Soc. 1994,
116, 5510. (b) McWilliams, J. C.; Clardy, J. J. Am. Chem. Soc.
18
epimeric mixture of (3S)-hydroxylactone 12, [α]
–28.7 (c 0.90,
D

736
LETTERS
SYNLETT
3H, J = 6.9 Hz), 1.30-1.18 (m, 1H), 1.02 (d, 3H, J = 7.0 Hz);
172.6, 138.3, 128.4, 127.6, 78.4, 75.3, 73.2, 71.4, 40.8, 39.6, 38.3,
32.1, 27.7, 21.0, 13.7. 13: 7.36-7.27 (m, 5H), 4.46 (s, 2H), 4.47 (q,
1H, J = 7.8 Hz), 3.99 (br s, 1H), 3.60 (dd, 1H, J = 9.0, 4.6 Hz),
3.38 (dd, 1H, J = 9.0, 4.0 Hz), 2.84 (dd, 1H, J = 13.0, 1.8 Hz),
2.68 (dd, 1H, J = 13.0, 6.3 Hz), 2.11 (br s, 1H), 2.04-1.97 (m, 1H),
1.78-1.61 (m, 4H), 1.20-1.16 (dt, 1H, J = 14.4, 4.1 Hz), 1.11 (d,
3H, J = 7.1 Hz), 1.02 (d, 3H, J = 7.1 Hz); 172.8, 138.3, 128.4,
127.8, 78.5, 73.2, 71.4, 53.5, 39.1, 38.3, 38.1, 32.0, 23.8, 21.7,
13.9. 14: 4.37 (ddd, 1H, J = 10.8, 8.0, 4.0 Hz), 3.94 (dt, 1H, J =
6.5, 2.0 Hz), 3.76 (br d, 1H, J = 10.5 Hz), 3.59 (br d, 1H, J = 10.5
Hz), 2.72 (dd, 1H, J = 12.6, 2.3 Hz), 2.65 (dd, 1H, J = 12.6, 6.6
Hz), 2.04-1.85 (m, 2H), 1.75-1.62 (m, 3H), 1.12 (dt, 1H, J = 15.3,
4.3 Hz), 1.03 (d, 3H, J = 7.1 Hz), 1.00 (d, 3H, J = 7.1 Hz), 0.91 (s,
9H), 0.17 (s, 3H), 0.05 (s, 3H); 171.7, 79.2, 73.0, 64.5, 40.3, 39.8,
38.7, 31.6, 25.8, 23.6, 21.0, 18.1, 13.6, –4.2, –5.2. 2 (R = TBS):
9.73 (d, 1H, J = 1.4 Hz), 4.65 (ddd, 1H, J = 11.9, 7.3, 3.2 Hz), 3.96
(d, 1H, J = 6.6 Hz), 2.78 (dd, 1H, J = 12.8, 1.8 Hz), 2.74 (dt, 1H, J
= 1.6, 7.3 Hz), 2.69 (dd, 1H, J = 12.8, 6.6 Hz), 2.02-1.93 (m, 1H),
1.78-1.54 (m, 5H), 1.13 (d, 3H, J = 7.6 Hz), 1.04 (d, 3H, J = 7.1
Hz), 0.91 (s, 9H), 0.18 (s, 3H), 0.05 (s, 3H); 202.4, 170.8, 72.8,
50.6, 39.7, 38.6, 31.4, 25.8, 23.1, 21.5, 18.1, 10.5, –4.2, –5.1.
1994, 116, 8378. (c) Bach, J.; Berenguer, R.; Garcia, J.; Vilarrasa,
J. Tetrahedron Lett. 1995, 36, 3425. (d) Buszek, K. R.; Jeong, Y.
Tetrahedron Lett. 1995, 36, 7189. (e) Andrus, M. B.; Argade, A.
B. Tetrahedron Lett. 1996, 37, 5049. (f) Kodama, M.; Matsushita,
M.; Terada, Y.; Takeuchi, A.; Yoshio, S.; Fukuyama, Y. Chem.
Lett. 1997, 117. (g) Hulme, A. N.; Howells, G. E. Tetrahedron
Lett. 1997, 38, 8245.
(6) Gao, Y.; Hanson, R. M.; Klunder, J. M.; Ko, S. Y.; Masamune, H.;
Sharpless, K. B. J. Org. Chem. 1987, 109, 5765.
(7) This operation was neccessary to remove the corresponding 1,2-
diol.
(3) For a recent review on SmI promoted reactions, see: Molander,
2
(8) Dess, D. B.; Martin, J. C. J. Org. Chem. 1983, 48, 4156.
G. A.; Harris, C. R. Chem. Rev. 1996, 96, 307.
(9) Swern oxidation of 12 always produced 9-benzyloxy-2,2-
dichloro-4,8-dimethyl-3-oxo-7-nonanolide as a major product due
to chlorination of initially formed 9-benzyloxy-4,8-dimethyl-3-
oxo-7-nonanolide.
(4) Tabuchi, T.; Kawamura, K.; Inanaga, J.; Yamaguchi, M.
Tetrahedron Lett. 1986, 27, 3889.
1
13
(5) All new compounds exhibited satisfactory spectral ( H and
C
1
NMR, IR, HRMS) data. Selected H NMR (500 MHz, CDCl )
and C NMR (125 MHz, CDCl ) data are following. 12: 7.35-
3
13
(10) Reduction of the corresponding β-keto lactone proceeded with
complete diastereoselectivity. This stereochemical outcome could
arise from the conformational rigidity of the eight-membered β-
keto lactone ring system. Cf.: Petasis, N. A.; Patane, M. A. J.
Chem. Soc., Chem. Commun. 1990, 836.
3
7.25 (m, 5H), 4.54 (q, 1H, J = 7.6 Hz), 4.47 (s, 2H), 3.56 (dd, 1H,
J = 9.3, 4.8 Hz), 3.53 (dt, 1H, J = 4.3, 10.1 Hz), 3.39 (dd, 1H, J =
9.3, 4.3 Hz), 2.78 (t, 1H, J = 12.1 Hz), 2.73 (dd, 1H, J = 12.1, 4.3
Hz), 2.36 (br s, 1H), 2.08-1.98 (m, 1H), 1.72-1.64 (m, 2H), 1.52
(dq, 1H, J = 9.5, 6.9 Hz), 1.45 (dt, 1H, J = 15.8, 4.1 Hz), 1.10 (d,
(11) The specific rotation was measured by Clardy and McWilliams.