Carbohydrate-based synthesis of naturally occurring marine metabolites slagenins B and C

Article abstract of DOI:10.1021/ol020112q

(graph presented) The first enantioselective syntheses of slagenins B and C, marine metabolites from Agelas nakamurai, starting from L-arabinose have been described.

Full text of DOI:10.1021/ol020112q

ORGANIC
LETTERS
2002
Vol. 4, No. 21
3569-3570
Carbohydrate-Based Synthesis of
Naturally Occurring Marine Metabolites
Slagenins B and C
Mukund K. Gurjar* and Smritilekha Bera
National Chemical Laboratory, Pune- 411008, India
gurjar@dalton.ncl.res.in
Received June 10, 2002
ABSTRACT
The first enantioselective syntheses of slagenins B and C, marine metabolites from Agelas nakamurai, starting from L-arabinose have been
described.
The secondary marine metabolites slagenins A (1), B (2),
and C (3) were isolated from the sponge Agelas nakamurai.1
These natural products possess cytotoxicity against murine
leukemia L1210 cells in vitro with IC50 values of 7.5 and
7.0 µg/mL. They are characterized by the presence of a
tetrahydrofuro[2,3-d]imidazolidin-2-one moiety. Two groups
have reported synthesis of these metabolites. The first
synthesis described by Horne and co-workers2 involved
racemic preparations of slagenins, while a report from Jiang
et al.3 revealed synthesis of the antipodes of slagenins B
and C. The latter group, on the basis of NMR studies and
optical rotation values, suggested the absolute stereo-
chemistries as (9R,11R,15R) for slagenin B (2) and (9R,-
11S,15S) for slagenin C (3). We report in this letter the
The known4 5-O-tert-butyldiphenylsilyl-1,2-O-isopropy-
first enantioselective total synthesis of naturally occurring
slagenins B and C starting from L-arabinose as a chiral
precursor.
lidene-â-L-arabinofuranose (4) was subjected to Barton,s
deoxygenation reaction5 in which 4 was first converted into
the xanthate derivative (5) and then treated with tri n-butyltin
hydride in refluxing toluene to give the 3-deoxy derivative
(1) Tusda, M.; Uemoto, H.; Kobayashi, J. Tetrahedron Lett. 1999, 40,
5709.
(6). In the 1H NMR spectrum of 6, the characteristic signals
(2) Sosa, A. C. B.; Yakushijin, K.; Horne, D. A. Org. Lett. 2000, 2,
due to H-3 and H-3′ were located at 1.97 and 2.11 ppm.
3443.
(3) Jiang, B.; Liu, J. F.; Zhao, S. Y. Org. Lett. 2001, 3, 40.
(4) Dahlman, O.; Garegg, P. J.; Meyer, H.; Schramek, S. Acta Chem.
Scand, Ser. B. 1986, 40, 15.
(5) Barton, D. H. R.; McCombie, S. W. J. Chem. Soc., Perkin Trans. 1
1975, 1574.
10.1021/ol020112q CCC: $22.00 © 2002 American Chemical Society
Published on Web 09/18/2002

Transformation of 6 into the azido derivative 96 involved
removal of the silyl group, O-tosylation, and nucleophilic
displacement with NaN3 in DMF (Scheme 1).
diastereomers (12 and 13). Separation of this diastereomeric
mixture at this juncture was difficult. Therefore, the mixture
as such was subjected to catalytic reduction over Pd/C
followed by reaction with 4-bromo-2-(trichloroacetyl)pyrrole
in DMF at room temperature, which gave a mixture of 2
and 3 (Scheme 3).
Scheme 1a
Scheme 3a
a Reagents and conditions: (a) ref 4; (b) NaH, CS2, MeI, THF,
rt, 2 h (98%); (c) Bu3SnH, toluene AIBN, reflux, 5 h, (84%); (d)
1 M Bu4NF, THF rt, 4 h, (81%); (e) p-Ts-Cl, Et3N, CH2Cl2, rt,
(92%); (f) NaN3, DMF, 85 °C, 12 h, (85%).
a Reagents and conditions: (a) urea, 40% aq HF, MeOH, rt
(62%); (b) 10% Pd-C, H2, MeOH, 1 atm, 2 h (100%); 4-bromo-
2-trichloroacetyl-pyrrole, DMF, rt, 16 h, (83%); (c) chromatography.
Our next goal was to introduce an imidazolidine ring
system across the C1-C2 segment of 9. For this endeavor,
the isopropylidene group was cleaved under acidic conditions
and the resulting diol was selectively silylated with TBSCl-
imidazole to give 10. Swern oxidation7 of 10 provided the
2-ulose derivative (11) whose 1H NMR spectrum showed a
downfield shift of protons located at C-1 and C-3 (Scheme
2).
Silica gel chromatography conveniently provided slagenin
B (2) and C (3) as pure products. Slagenins B and C were
fully characterized by 1H and 13C NMR spectroscopic data,9
which were found to be identical to reported values.1 The
observed optical rotation of synthetic slagenin B (2) was [R]D
+ 36 (c 0.2, MeOH) [lit.1 [R]D + 33 (c 0.2, MeOH)], and
that of slagenin C (3) was [R]D -39 (c 0.2, MeOH) [lit.1
[R]D -35 (c 0.2, MeOH)]. In summary, a carbohydrate-based
synthesis of naturally occurring slagenins B and C have been
reported starting from L-arabinose.
Scheme 2a
Acknowledgment. S.B. thanks CSIR (New Delhi) for
financial assistance in the form of a Senior Research
Fellowship.
a Reagents and conditions: (a) TBSCl, imidazole, Et3N, CH2Cl2,
45 min (72%); (b) (COCl)2, DMSO, Et3N, 2 h (72%).
Supporting Information Available: 1H NMR and 13C
NMR spectra for 10, 11, 2, and 3. This material is available
free of charge via the Internet at http://pubs.acs.org.
Treatment8 of 11 with urea in the presence of 40% aqueous
HF in methanol at room temperature gave a mixture of
OL020112Q
(6) Selected spectroscopic values for 9: 1H NMR (CDCl3, 200 MHz):
δ 1.26 (s, 3 H), 1.50 (s, 3 H), 1.97 (dd, 1 H, J ) 2.9, 15.1 Hz), 2.11 (ddd,
1 H, J ) 5.7, 7.5, 15.1 Hz), 3.16 (dd, 1 H, J ) 6.8, 12.4 Hz), 3.61 (dd, 1
H, J ) 7.5, 12.4 Hz), 4.23 (m, 1 H), 4.67 (m, 1 H), 5.61 (d, 1 H, J ) 4.2
Hz). 13C NMR (CDCl3, 50 MHz): δ 25.8, 27.0, 34.4, 54.72, 79.6, 80.5,
106.7, 112.3. Ms: 184 (M+ - 15); IR: 2100 cm-1 (N3). Anal. Calcd for
C8H13N3O3: C, 48.24; H, 6.53. Found: C, 47.9; H, 6.56.
(9) NMR data. Slagenin B (2): 1H NMR (CDCl3, 500 MHz) δ 1.76 (t,
1 H, J ) 11.9 Hz), 2.17 (dd, 1 H, J ) 3.9, 11.9 Hz), 3.15 (s, 3 H), 3.48 (m,
2 H), 4.04 (m, 2 H), 5.19 (s, 1 H), 6.86 (d, 1 H, J ) 1.6 Hz), 6.96 (d, 1 H,
J ) 1.6 Hz), 7.50 (s, 1 H), 8.42 (t, 1 H, J ) 5.7 Hz); 13C NMR (CDCl3,
125 MHz) δ 41.5, 41.6, 50.3, 76.1, 88.5, 94.8, 97.9, 112.0, 121.3, 126.8,
155.5, 159.8. Slagenin C (3): 1H NMR (CDCl3, 200 MHz) δ 1.90 (dd, 1
H, J ) 6.4, 12.8 Hz), 2.29 (dd, 1 H, J ) 6.7, 12.8 Hz), 3.17 (s, 3 H), 3.40
(m, 2 H), 4.19 (m, 1 H), 5.12 (s, 1 H), 6.87 (s, 1 H), 6.97 (s, 1 H) 7.65 (s,
1 H), 7.69 (s, 1 H), 8.24 (t, 1 H, J ) 5.1 Hz), 11.87 (s, 1 H); 13C NMR
(CDCl3, 50 MHz) 40.8, 42.9, 49.8, 76.2, 89.5, 95, 97.3, 111.8, 121.2, 126.8,
159.4, 159.7.
(7) Omura, K.; Swern, D. Tetrahedron 1978, 34, 1651.
(8) (a) Grillon, E.; Gallo, R.; Pierrot, M.; Boileau, J.; Wimmer, E.
Tetrahedron Lett. 1998, 29, 1015. (b) Gautam, S.; Katcham, R.; Nematullahi,
J. Synthetic Comm. 1979, 9, 863.
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