Metathesis route to resin glycosides: Formal total synthesis of tricolorin A

Full text of DOI:10.1021/jo971918k

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24
J . Org. Chem. 1998, 63, 424-425
Meta th esis Rou te to Resin Glycosid es:
F or m a l Tota l Syn th esis of Tr icolor in A
Alois F u¨ rstner* and Thomas M u¨ ller
Max-Planck-Institut f u¨ r Kohlenforschung
Kaiser-Wilhelm-Platz 1, D-45470 M u¨ lheim/ Ruhr, Germany
Received October 17, 1997
The tricolorin family of resin glycosides constitutes the
allelochemical principle of Ipomoea tricolor Cav., a plant that
is extensively used in traditional agriculture in Mexico as a
cover crop for the protection of sugar cane.1 Tricolorin A
F igu r e 1.
,2
(
1) was also found to exhibit significant cytotoxic properties
closing metathesis (RCM) for the formation of the macro-
cycle. This strategy has the inherent advantage that
systematic variations of the ring size and hence of the
lipophilicity of the compound are easy to accomplish.
Our previous investigations on RCM have uncovered the
essential requirements for productive macrocyclizations and
1
against cultured P-388 and human breast cancer cell lines.
To probe this promising activity in more detail, a synthesis-
driven mapping of its structure/activity profile is called for,
which can only be achieved on the basis of a convergent
approach to these complex oligosaccharide targets. The
major challenge toward this end is posed by the macrolide
entity formed by (11S)-hydroxyhexadecanoic acid spanning
two (cf. 1) or more (cf. 2) units of their sugar backbones.
4
-6
have revealed a truly remarkable scope of this method.
We found that neither the conformational predisposition of
the substrates nor the ring size formed is of major concern,
whereas the mere presence of a polar “relay” substituent,
its proper distance to the alkene groups, and low steric
hindrance close to the double bonds turned out to be the
decisive parameters.4 It should be possible to meet all of
these criteria en route to 3, provided that the large ring is
closed at (or near) the site indicated in Figure 1.
The synthesis of the required fucose building block is
shown in Scheme 1. Enantioselective addition of dipentyl-
zinc to 5-hexenal (4) in the presence of Ti(O-i-Pr)4 and
catalytic amounts of bis-(R,R)-trifluoromethanesulfonamide
5
proceeded smoothly on a multigram scale, providing (S)-6
7
in good yield and excellent enantiomeric purity (ee g 99%).
(3) (a) Larson, D. P.; Heathcock, C. H. J . Org. Chem. 1996, 61, 5208. (b)
Very recently a total synthesis of tricolorin A has been reported using
compound 3 as a key intermediate, cf.: Lu, S.-F.; O’yang, Q.; Guo, Z.-W.;
Yu, B.; Hui, Y.-Z. Angew. Chem. 1997, 109, 2442. (c) For a seminal total
synthesis of another resin glycoside see: J iang, Z.-H.; Geyer, A.; Schmidt,
R. R. Angew. Chem. 1995, 107, 2730.
(4) (a) F u¨ rstner, A.; Langemann, K. J . Org. Chem. 1996, 61, 3942. (b)
F u¨ rstner, A.; Langemann, K. Synthesis 1997, 792. (c) F u¨ rstner, A.; Kindler,
N. Tetrahedron Lett. 1996, 7005. (d) F u¨ rstner, A.; Langemann, K. J . Org.
Chem. 1996, 61, 8746. (e) F u¨ rstner, A.; M u¨ ller, Th. Synlett 1997, 1010. (f)
F u¨ rstner, A.; Langemann, K. J . Am. Chem. Soc. 1997, 119, 9130. (g)
F u¨ rstner, A.; Koch, D.; Langemann, K.; Leitner, W.; Six, Ch. Angew. Chem.
1
997, 109, 2562.
5) For other macrocyclizations via RCM see the following for leading
(
references: (a) Miller, S. J .; Blackwell, H. E.; Grubbs, R. H. J . Am. Chem.
Soc. 1996, 118, 9606. (b) Clark, T. D.; Ghadiri, M. R. J . Am. Chem. Soc.
1
995, 117, 12364. (c) K o¨ nig, B.; Horn, C. Synlett 1996, 1013. (d) McKervey,
M. A.; Pitarch, M. J . Chem. Soc. Chem. Commun. 1996, 1689. (e) Yang, Z.;
He, Y.; Vourloumis, D.; Vallberg, H.; Nicolaou, K. C. Angew. Chem. 1997,
1
09, 170. (f) Nicolaou, K. C.; He, Y.; Vourloumis, D.; Vallberg, H.; Yang, Z.
Angew. Chem. 1996, 108, 2554. (g) Schinzer, D.; Limberg, A.; Bauer, A.;
B o¨ hm, O. M.; Cordes, M. Angew. Chem. 1997, 109, 543. (h) Bertinato, P.;
Sorensen, E. J .; Meng, D.; Danishefsky, S. J . J . Org. Chem. 1996, 61, 8000.
(
1
i) Houri, A. F.; Xu, Z.; Cogan, D. A.; Hoveyda, A. H. J . Am. Chem. Soc.
995, 117, 2943. (j) Martin, S. F.; Liao, Y.; Chen, H.-J .; P a¨ tzel, M.; Ramser,
In recent studies directed toward the tricolorins, syntheses
of the disaccharidic fragment 3 of tricolorin A via macro-
M. N. Tetrahedron Lett. 1994, 6005. (k) Villemin, D. Tetrahedron Lett. 1980,
1715. (l) Descotes, G.; Ramza, J .; Basset, J .-M.; Pagano, S.; Gentil, E.;
Banoub, J . Tetrahedron 1996, 52, 10903. (m) Meng, D.; Bertinato, P.; Balog,
A.; Su, D.-S.; Kamenecka, T.; Sorensen, E. J .; Danishefsky, S. J . J . Am.
Chem. Soc. 1997, 119, 10073.
lactonization as the key step have been described.3
a,b
We
now report an alternative approach to 3 employing ring
*
To whom correspondence should be addressed. E-mail: fuerstner@mpi-
muelheim.mpg.de.
1) (a) Pereda-Miranda, R.; Mata, R.; Anaya, A. L.; Wickramaratne, M.;
(6) For reviews see: (a) Grubbs, R. H.; Miller, S. J .; Fu, G. C. Acc. Chem.
Res. 1995, 28, 446. (b) F u¨ rstner, A. Top. Catal., in press.
(7) (a) Takahashi, H.; Kawakita, T.; Ohno, M.; Yoshioka, M.; Kobayashi,
S. Tetrahedron 1992, 48, 5691. (b) Knochel, P. in Active Metals. Preparation,
Characterization, Applications; F u¨ rstner, A., Ed.; VCH: Weinheim, 1996;
p 191. (c) Knochel, P. Synlett 1995, 393. (d) Noyori, R. Asymmetric Catalysis
in Organic Synthesis; Wiley: New York, 1994; p 255.
(
Pezzuto, J . M.; Kinghorn, A. D. J . Nat. Prod. 1993, 56, 571. (b) Bah, M.;
Pereda-Miranda, R. Tetrahedron 1996, 52, 13063. (c) Bah, M.; Pereda-
Miranda, R. Tetrahedron 1997, 53, 9007.
(2) For references on other resin glycosides see: (a) Noda, N.; Ono, M.;
Miyahara, K.; Kawasaki, T.; Okabe, M. Tetrahedron 1987, 43, 3889. (b)
Noda, N.; Tsuji, K.; Kawasaki, T.; Miyahara, K.; Hanazono, H.; Yang, C.-
R. Chem. Pharm. Bull. 1995, 43, 1061. (c) Kitagawa, I.; Baek, N. I.;
Kawashima, K.; Yokokawa, Y.; Yoshikawa, M.; Ohashi, K.; Shibuya, H.
Chem. Pharm. Bull. 1996, 44, 1680 and literature cited therein.
2
(8) Prepared from D-fucose by acetylation (Ac O, DMAP, pyridine, 98%)
and subsequent treatment with HBr (33% in HOAc) in Ac O/CH Cl at 0
2 2 2
°C f rt.
(9) Van Boeckel, C. A. A.; Beetz, T.; Kock-van Dalen, A. C.; van Bekkum,
H. Recl. Trav. Chim. Pays-Bas 1987, 106, 596.
S0022-3263(97)01918-X CCC: $15.00 © 1998 American Chemical Society
Published on Web 01/16/1998

Communications
J . Org. Chem., Vol. 63, No. 3, 1998 425
Sch em e 1a
Sch em e 2a
a
Key: (a) reagents as indicated, toluene, rt; (b) AgNO
Cl , -10 °C; (c) KOMe cat., MeOH, rt; (d) 2,2-
dimethoxypropane, p-TsOH‚H O cat., acetone, rt.
3
on silica/
alumina,9 MS 3 Å, CH
2
2
2
Its glycosylation with tri-O-acetyl-R-D-fucopyranosyl bromide
(
7) in the presence of AgNO3 on silica/alumina9 gave
8
compound 8 in 69% yield, which was deacetylated (8 f 9)
and converted into acetal 10 under standard conditions.
The other monosaccharide unit was obtained from 4,6-O-
benzylidene-D-glucopyranose (11)10 as outlined in Scheme
2
. Peracetylation of 11 followed by deprotection of the
3
a
a
anomeric position gave compound 13, which readily af-
forded trichloroacetimidate 14 on treatment with Cl3CCN
and Cs2CO3 in CH2Cl2. Reaction of this glycosyl donor (R:â
Ket: (a) Ac
°C f rt; (ii) 1 N HCl; (c) Cl
cat., CH Cl /n-hexane (1/1), -20 °C; (e) KOMe cat., MeOH, rt; (f)
-heptenoic Acid, DCC, DMAP, CH Cl , rt; (g) 18 (5 mol %), CH Cl
reflux, high dilution; (h) H (1 atm), Pd/C (5 mol %), EtOH, rt.
2
O, DMAP cat., pyridine, 0 °C f rt; (b) (i) BnNH
2
, THF,
0
3
CCN, Cs CO , CH Cl , rt; (d) 10, BF
2
3
2
2
3
‚Et
2
O
2
2
6
2
2
2
2
,
≈
2:1) with the fucose derivative 10 in CH2Cl2/hexane at
20 °C in the presence of catalytic amounts of BF3‚Et2O
2
-
catalyst.6 Hydrogenation of the crude cycloalkene 19 (E/Z-
mixture) afforded the desired disaccharide 3 in 77% yield
over both steps and completes a formal total synthesis of
tricolorin A.3b Among the analytical and spectroscopic data
of 3, the strong solvent dependence of its H NMR spectrum
is most remarkable (cf. Supporting Information).
The direct comparison of the metathesis route to 3 with
the macrolactonization strategy previously reported confirms
our earlier findings that RCM rivals all established methods
for the synthesis of large rings, provided that the proper site
cleanly provided the desired â-configurated disaccharide 15
in 82% yield.11 Deprotection followed by acylation of the
resulting diol 16 with 6-heptenoic acid in the presence of
DCC and DMAP proceeded selectively at the O-3 position,
thus affording ester 17 as the only product in 71% yield.
The site of acylation was unambiguously assigned by NMR
and the reactivity pattern O-3 . O-2 in diol 16 is in full
accordance with Heathcock’s observations in his macrolac-
1
3
a
tonization approach toward compound 3.
4
In line with our previous experiences, diene 17 cleanly
4
of ring closure is chosen according to our previous rationale.
cyclized to the desired 19-membered ring 19 on reaction with
the ruthenium carbene 18 (5 mol %)12 in refluxing CH2Cl2.
Moreover, it is obvious that esterification of diol 16 with
acids other than 6-heptenoic acid or attachment of such an
unsaturated appendage at other sites of the sugar backbone
opens up a flexible entry into congeners and analogues of
tricolorin A.
Ack n ow led gm en t. Th.M. thanks the Fonds der Che-
mischen Industrie, Frankfurt, for a Kekul e´ stipend.
The fact that neither the free OH nor any other functional
group in the substrate interfere with RCM illustrates again
the excellent compatibility and selectivity of the Grubbs
Su p p or tin g In for m a tion Ava ila ble: Procedures for all steps,
details of ee determination, analytical data, and copies of the NMR
spectra of all new products (34 pages).
J O971918K
(
10) Barili, P. L.; Berti, G.; Catelani, G.; Cini, C.; D’Andrea, F.; Mastro-
rilli, E. Carbohydr. Res. 1995, 278, 43.
11) For reviews see: (a) Schmidt, R. R. Angew. Chem., Int. Ed. Engl.
1
1
(
(12) (a) Nguyen, S. T.; Grubbs, R. H.; Ziller, J . W. J . Am. Chem. Soc.
1993, 115, 9858. (b) Nguyen, S. T.; J ohnson, L. K.; Grubbs, R. H.; Ziller, J .
W. J . Am. Chem. Soc. 1992, 114, 3974.
986, 25, 212. (b) Schmidt, R. R.; Kinzy, W. Adv. Carbohydr. Chem. Biochem.
994, 50, 21.