Cross-linking dendrimers with allyl ether end-groups using the ring-closing metathesis reaction

Article abstract of DOI:10.1021/jo049368v

A third generation Frechet-type dendrimer containing 24 allyl ether end-groups was synthesized, cross-linked using the ring-closing metathesis (RCM) reaction, and the core was removed hydrolytically without significant fragmentation. The results are analo

Full text of DOI:10.1021/jo049368v

the ring-closing metathesis (RCM) reaction7 of homoallyl
ether end-groups.1,3,6 There are a few notable exceptions
wherein other types of alkenes are cross-linked via the
RCM reaction4,5,8 and entirely different cross-linking
chemistries employed.9
Cr oss-Lin k in g Den d r im er s w ith Allyl Eth er
En d -Gr ou p s Usin g th e Rin g-Closin g
Meta th esis Rea ction
Stephanie L. Elmer and Steven C. Zimmerman*
The choice of the homoallyl ether over the allyl ether
group was motivated by the concern that the latter might
undergo undesired side reactions. In particular, the
possibility for isomerization to a vinyl ether group that
would deactivate the catalyst by forming an unreactive
ruthenium carbene10 was a compelling reason to choose
the homoallyl group. Despite these concerns, and since
our report on cored dendrimers appeared,1 numerous
examples of metathesis reactions of allyl ethers were
reported.11 Furthermore, there was considerable interest
in pursuing dendrimers with allyl ether end-groups both
to increase the structural diversity of host molecules that
could be used for MIDs and because of the obvious cost
advantages of the allyl-based starting materials. For
these reasons, we prepared allyl and homoallyl ether-
based dendrimers as macromolecular hosts12 and herein
report the synthesis of 6, the 6 f 7 f 8 interconversion,
and a direct comparison to our previously reported
chemistry.1 The results suggest that the allyl ether group
is an excellent replacement for the homoallyl ether-based
end group.
Department of Chemistry, 600 S. Mathews Avenue,
University of Illinois, Urbana, Illinois 61801
sczimmer@uiuc.edu
Received April 15, 2004
Ab st r a ct : A third generation Fre´chet-type dendrimer
containing 24 allyl ether end-groups was synthesized, cross-
linked using the ring-closing metathesis (RCM) reaction, and
the core was removed hydrolytically without significant
fragmentation. The results are analogous to those previously
reported for homoallyl ether dendrimers (Wendland, M. S.;
Zimmerman, S. C. J . Am. Chem. Soc. 1999, 121, 1389-1390)
suggesting that the less readily available homoallyl ether
dendrimers can be replaced by their allyl ethers analogues
in a range of applications.
In tr od u ction
We recently reported the synthesis of dendrimers
whose cores are removed. For example, the end-groups
of dendrimer 1 were extensively cross-linked with 2 to
give 3 whose trimesic acid core (4) was removed hydro-
lytically giving “cored” dendrimer 5 (Scheme 1).1,2 There
are a number of potential applications for the resultant
nanoparticles, for example, as higher capacity drug
delivery agents and as molecularly imprinted dendrimers
(MIDs).3 The dendrimer cross-linking chemistry alone or
in combination with coring can also be used to form a
stable shell around metallic nanoparticles,4 to rigidify the
binding sites in molecularly imprinted polymers,5 and to
create organic nanotubes by a “molding” process.6 Most
commonly, the cross-linking of dendrimers has involved
Resu lts a n d Discu ssion
The synthesis of dendrimer 6 is outlined in Schemes
2-4. The reported synthesis of 11 used the Mitsunobu
etherification reaction,13 following literature prece-
dent.14,15 The Williamson etherification approach was
explored for the allyl ether-based dendrimer 6. Thus,
treatment of 9 with allyl bromide and base afforded 10
in near quantitative yield (Scheme 2). However, as 10
was carried forward in the synthesis, increasingly an
inseparable impurity revealed itself in the 1H NMR.
Careful analysis of 10 showed it to contain ca. 2-3% of
over-alkylated product 11 whose presence becomes am-
(1) Wendland, M. S.; Zimmerman, S. C. J . Am. Chem. Soc. 1999,
121, 1389-1390.
(7) Selected papers on Ru carbene-mediated RCM reactions: (a)
Grubbs, R. H.; Miller, S. J .; Fu, G. C. Acc. Chem. Res. 1995, 28, 446-
452. (b) Fu¨rstner, A. Top. Catal. 1997, 4, 285-299. (c) Hoveyda, A. H.
Top. Organomet. Chem. 1998, 1, 105-132. (d) Grubbs, R. H.; Trnka,
T. M.; Sanford, M. S. Curr. Methods Inorg. Chem. 2003, 3, 187-231.
(8) Schultz, L. G.; Zhao, Y.; Zimmerman, S. C. Angew. Chem., Int.
Ed. 2001, 40, 1962-1966.
(2) Monographs on dendrimers: Fre´chet, J . M. J .; Tomalia, D. A.
Dendrimers and Other Dendritic Polymers; Wiley: New York, 2001.
Newkome, G. R.; Moorefield, C. N.; Vo¨gtle, F. Dendrimer and Den-
drons: Concepts, Syntheses, Applications; VCH: Weinheim, Germany,
2001. Selected reviews on the supramolecular chemistry of dendrim-
ers: Zeng, F.; Zimmerman, S. C. Chem. Rev. 1997, 97, 1681-1712.
Newkome, G. R.; He, E.; Moorefield, C. N. Chem. Rev. 1999, 99, 1689-
1746. Baars, M. W. P. L.; Meijer, E. W. Top. Curr. Chem. 2000, 210,
131-182. Smith, D. K.; Diederich, F. Top. Curr. Chem. 2000, 210, 183-
227. Gorman, C. B.; Smith, J . C. Acc. Chem. Res. 2001, 34, 60-71.
Zimmerman, S. C.; Lawless, L. J . Top. Curr. Chem. 2001, 217, 95-
120.
(9) For an example of a photocross-linking process, see: Wang, J .;
J ia, X.; Zhong, H.; Wu, H.; Li, Y.; Xu, X.; Li, M.; Wei, Y. J . Polym. Sci.
A-Polym. Chem. 2000, 38, 4147-4153.
(10) (a) Coates, G. W., personal communication, 1996. (b) Wu, Z.;
Nguyen, S. T.; Grubbs, R. H.; Ziller, J . W. J . Am. Chem. Soc. 1995,
117, 5503-5511. (b) For recent reviews of nonmetathetic reactions
shown by the Grubbs’ ruthenium carbene catalysts, see: Schmidt, B.
Eur. J . Org. Chem. 2004, 1865-1880. Alcaide, B.; Almendros, P. Chem.
Eur. J . 2003, 9, 1258-1262.
(11) Chatterjee, A. K.; Choi, T.-L.; Sanders, D. P.; Grubbs, R. H. J .
Am. Chem. Soc. 2003, 125, 11360-11370 and references therein.
(12) Mertz, E.; Elmer, S. L.; Zimmerman, S. C., Tetrahedron,
accepted for publication.
(3) Zimmerman, S. C.; Wendland, M. S.; Rakow, N. A.; Zharov, I.;
Suslick, K. S. Nature 2002, 418, 399-403. Mertz, E.; Zimmerman, S.
C. J . Am. Chem. Soc. 2003, 125, 3424-3425. Zimmerman, S. C.;
Zharov, I.; Wendland, M. S.; Rakow, N. A.; Suslick, K. S. J . Am. Chem.
Soc. 2003, 125, 13504-13518. Zimmerman, S. C.; Lemcoff, N. G. Chem.
Commun. 2004, 5-14. Beil, J . B.; Zimmerman, S. C. Chem. Commun.
2004, 488-489.
(13) Mitsunobu, O. Synthesis 1981, 1-28. Hughes, D. L. Org. React.
(4) Guo, W.; Li, J . J .; Wang Y. A.; Peng, X. J . Am. Chem. Soc. 2003,
125, 3901-3909.
1992, 42, 335-656.
(14) Zimmerman, S. C.; Zeng, F.; Reichert, D. E. C.; Kolotuchin, S.
V. Science 1996, 271, 1095-1098. Zeng, F.; Zimmerman, S. C. J . Am.
Chem. Soc. 1996, 118, 5326-5327.
(5) Becker, J . J .; Gagne´, M. R. Organometallics 2003, 22, 4984-
4998.
(6) Kim, Y.; Mayer, M. F.; Zimmerman, S. C. Angew. Chem., Int.
Ed. 2003, 42, 1121-1126.
(15) Ho¨ger, S. Synthesis 1997, 20-22. (b) L’Abbe’, G.; Forier, B.;
Dehaen, W. Chem. Commun. 1996, 2143-2144.
10.1021/jo049368v CCC: $27.50 © 2004 American Chemical Society
Published on Web 09/11/2004
J . Org. Chem. 2004, 69, 7363-7366
7363

SCHEME 1
SCHEME 2
SCHEME 3. Syn th esis of Den d r on 14 via
Mitsu n obu Ap p r oa ch a
plified as the dendrimer surface grows. A similar problem
with over-alkylation using the Williamson etherification
has been noted previously.16,17 Careful purification of 10
by silica chromatography removed 11 and afforded pure
10 in 95% yield.
In the synthesis of 1, the Mitsunobu approach was
found to give only trace amounts of the C-alkylation
byproducts. As shown in Scheme 3, ester 10 could also
be produced by Mitsunobu coupling of 9 with homoallyl
alcohol with only a trace of C-alkylation; however, the
yield was only 74%. The yield was only 74%. The
Mitsunobu protocol proved superior for subsequent steps
(vide supra), but for this first step, the procedure in
Scheme 2 was utilized on a large scale with the careful
chromatographic purification. Reduction of 10 with lithium
aluminum hydride afforded alcohol 12 in 92% yield.
Mitsunobu coupling of 12 with 9 afforded the second
generation methyl ester 13 in 98% yield. The third
generation methyl ester 15 was produced by lithium
aluminum hydride reduction of 13 to afford 14 in 94%
yield followed by Mitsunobu coupling with 9 (90% yield).
Dendron 15, a key intermediate in the synthesis of
MIDs,3 was readily prepared on >10 g scale. As seen in
Schemes 2 and 3 preparation of 15 requires 5 steps from
9 and allyl bromide with an overall yield of 72%, whereas
the analogous homoallyl dendron was prepared in a lower
overall yield (35%) from 9 and the more expensive
homoallyl alcohol.1
a
Yields shown in parentheses are those obtained for analogous
reaction in homoallyl series (see ref 1).
(Scheme 4). The ring-closing metathesis reaction of
dendrimer 6 with three additions of 2 mol % Grubbs
ruthenium alkylidene catalyst 2 per alkene over 72 h
gave exclusively the intramolecular product 7 in 95%
yield when performed at a concentration of 10-5 M in
benzene. The progress of the RCM reaction could be
monitored by matrix-assisted laser desorption ionization
time-of-flight mass spectroscopy (MALDI-TOF-MS) and
additional portions of catalyst were added to the reaction
following the apparent loss of efficacy of the catalyst.
To examine whether the allyl ether end-groups would
undergo RCM-mediated cross-linking, dendron 15 was
reduced with lithium aluminum hydride (100% yield of
16) and reacted with trimesic acid (4) under Mitsunobu
esterification conditions to give dendrimer 6 in 76% yield
(16) Leon, J . W.; Kawa, M.; Fre´chet, J . M. J . Am. Chem. Soc. 1996,
118, 8847-8859.
(17) Wendland, M. S., Ph.D. Thesis, University of Illinois, 2001.
7364 J . Org. Chem., Vol. 69, No. 21, 2004

SCHEME 4. Syn th esis of Den d r im er 6a
methanol in THF (Scheme 4). The cored dendrimer 8 was
isolated in 83% yield indicating that the dendrimer
underwent significant intra-dendron cross-linking to hold
the macromolecular structure together after core re-
moval. Only a trace amount of fragmentation was ob-
served in the MALDI-TOF spectrum. The mass spectra
indicated that coring was quantitative with the primary
peak corresponding to the cored product with 12 of 12
cross-links and a very minor peak corresponding to the
product with 11 cross-links. The 1H NMR spectra clearly
showed the core removal with the disappearance of the
broad peak in the 9.20 to 8.80 ppm range corresponding
to the aromatic protons of the core. The SEC determined
Mw of 8 was 1570 Da, 52% below the MALDI-TOF-MS
measured actual MW. The SEC results indicated that
coring the dendrimer did not cause a significant change
in size.
Con clu sion
In conclusion, we synthesized a dendrimer containing
allyl ether end-groups that underwent complete cross-
linking and coring. Synthesis of this dendrimer proceeded
in a manner similar to the iterative Mitsunobu etheri-
fication-lithium aluminum hydride reduction protocol
employed with the analogous homoallyl ether end-group
dendrimer.1 Given that the yields were similar to and in
many cases higher than those obtained for the homoallyl
system and the allyl bromide starting material is con-
siderably less expensive, the allyl ether-based dendrons
and dendrimers are the clear choice of future applica-
tions.
a
Yields shown in parentheses are those obtained for analogous
reaction in homoallyl series (see ref 1). The coring of the homoallyl
series was carried out using the reagents shown in Scheme 1
TABLE 1. Com p a r ison of Th eor etica l to SEC a n d
MALDI-TOF -MS Deter m in ed Exp er im en ta l Molecu la r
Weigh ts
molecular weight
compd theoreta SECb MALDIc
peak assignment
Exp er im en ta l Section
6
7
3756.5
3420.2
3448.2
3264.2
3292.2
3750
1530
3753.0 M + Na+
3420.7 M + Na+ - 12C2H4
3,5-Bis(2-p r op en -1-oxy)ben zoic a cid m eth yl ester ([G-
1]-CO2Me) (10). A solution of 25.0 g (149 mmol) of dihydroxy-
benzoic acid methyl ester (9), 51 mL (595 mmol) of allyl bromide,
82.2 g (595 mmol) of K2CO3 and 3.90 g (15 mmol) of 18-crown-6
in 295 mL acetone was refluxed at 75 °C for 24 h. Acetone was
removed under reduced pressure. To the resultant solid was
added 200 mL of water. The aqueous layer was extracted with
Et2O (2 × 200 mL). The organic layers were combined and
washed with 200 mL of 15% (w/v) aqueous NaOH and an equal
volume of water. The organic layer was dried over sodium
sulfate, filtered, and evaporated. Purification by column chro-
matography (silica gel, 19:1 PE/EtOAc) afforded 10 as clear
crystals weighing 36.9 g (95%): 1H NMR (CDCl3, 500 MHz) δ
7.20 (d, 2H, J ) 2.5), 6.69 (t, 1H, J ) 2.5), 6.04 (ddt, 2H, J )
17.5, 11.0, 5.0), 5.42 (ddt, 2H, J ) 17.3, 1.6, 1.0), 5.23 (ddt, 2H,
J ) 10.5, 1.5, 1.0), 4.55 (ddd, 4H, J ) 5.5, 1.8, 1.5), 3.99 (s, 3H);
13C NMR (CDCl3, 126 MHz) δ 167.0, 159.8, 133.0, 132.2, 118.2,
108.3, 107.3, 69.2, 52.4; MS (FD) m/z 248.1 (MH+). Anal. Calc’d
for C14H16O4: C, 67.73; H, 6.50. Found: C, 67.68; H, 6.46.
Gen er a l P r oced u r e for LAH Red u ction . To a suspension
of lithium aluminum hydride (LAH) in THF cooled to 0 °C was
added dropwise a solution of the appropriate ester in THF. After
addition, the solution was allowed to warm to room temperature
and stirred for 24 h. Excess LAH was quenched by slow addition
of water followed by neutralization with 3 M aqueous HCl. The
THF was removed under reduced pressure. The resultant
aqueous solution was extracted with Et2O and each organic layer
was washed with an equal volume of water. The combined
organic layers were dried over sodium sulfate, filtered and
evaporated.
3449.8 M + Na+ - 11C2H4
8
1570
3266.5 M + Na+ - 12C2H4 - C9O3
3292.0 M + Na+ - 11C2H4 - C9O3
a
b
Calculated for indicated peak assignment. THF eluent with
polystyrene calibration. c M + K+ peaks are present but not shown.
Product 7 contained primarily 12 out of 12 possible cross-
links with a trace peak intensity corresponding to the
product with 11 cross-links (see Table 1 and the Sup-
porting Information).
Consistent with previous studies of cross-linked den-
drimers,1,3 the cross-linked dendrimer 7 eluted later than
the uncross-linked 6 on an analytical size-exclusion
chromatography (SEC) column. The SEC determined
MW of 7 was 1530 Da, 55% below the MALDI-TOF-MS
measured and the theoretical MW (Table 1). This un-
derestimation in the molecular weight of 7 indicates that
the cross-linked structure adopts a much more compact
shape with a smaller hydrodynamic radius. Additionally,
1
the H NMR spectra of 7 showed significant broadening
of signals due to the isomeric mixture formed during the
metathesis reaction. Despite broadening of the peaks, the
1H NMR spectra clearly indicated the formation of cross-
linked allyl ether groups in the 6.10 to 5.60 ppm range
and the disappearance of the terminal alkene proton
peaks at 5.37 and 5.24 ppm.
3,5-Bis(2-p r op en -1-oxy)ben zyl a lcoh ol ([G-1]-OH) (12).
Prepared according to the general reduction procedure using 11.4
g (301 mmol) of LAH in 239 mL of THF and 36.9 g (149 mmol)
of ester 10 dissolved in 150 mL of THF to afford 31.9 g (92%) of
The cross-linked dendrimer 7 was cored using a trans-
esterification reaction with potassium carbonate and
J . Org. Chem, Vol. 69, No. 21, 2004 7365

12 as a clear oil: 1H NMR (CDCl3, 400 MHz) δ 6.55 (d, 2H, J )
2.4), 6.43 (t, 1H, J ) 1.8), 6.05 (ddt, 2H, J ) 17.2, 10.4, 5.6),
5.41 (ddt, 2H, J ) 17.2, 1.6, 1.6), 5.28 (ddt, 2H, J ) 10.4, 1.6,
1.2), 4.62 (s, 2H), 4.52 (ddd, 4H, J ) 5.2, 1.6, 1.2); 13C NMR
(CDCl3, 100 MHz) δ 160.1, 143.5, 133.3, 118.0, 105.8, 101.4, 69.1,
65.4; MS (FD) m/z 220.2 (MH+).
Gen er a l P r oced u r e for Mitsu n obu Cou p lin g. To a mix-
ture at 0 °C of the appropriate alcohol, the appropriate ester or
acid and triphenylphosphine (PPh3) in THF was added dropwise
a solution of diisopropyl azodicarboxylate (DIAD) in THF. The
reaction warmed to room temperature and stirred for 24 h. The
reaction was stopped by adding water and evaporated to remove
THF. The aqueous layer was extracted with Et2O and each
organic layer was washed with 2.5 M aqueous KOH and an equal
volume of water. The combined organic layers were dried over
sodium sulfate, filtered and evaporated.
3,5-Bis[3,5-bis(2-p r op en -1-oxy)ben zyloxy)ben zoic a cid
m eth yl ester ([G-2]-CO2Me) (13). Prepared according to the
general Mitsunobu procedure using 10.9 g (50 mmol) of alcohol
12, 13.8 g (23 mmol) of ester 9, 14.8 g (56 mmol) of PPh3 in 50
mL of THF and 11.1 mL (56 mmol) of DIAD in 200 mL of THF.
Column chromatography (silica gel, 19:1 to 4:1 PE/EtOAc)
afforded 12.6 g (98%) of 13 as a clear oil: 1H NMR (CDCl3, 400
MHz) δ 7.27 (d, 2H, J ) 1.6), 6.77 (t, 1H, J ) 1.8), 6.59 (d, 4H,
J ) 1.6), 6.45 (t, 2H, J ) 2.0), 6.04 (ddt, 4H, J ) 13.6, 9.2, 3.6),
5.41 (ddt, 4H, J ) 13.8, 1.6, 1.2), 5.28 (ddt, 4H, J ) 8.4, 1.2,
1.2), 5.00 (s, 4H), 4.52 (ddd, 8H, J ) 4.0, 1.6, 1.2), 3.90 (s, 3H);
13C NMR (CDCl3, 126 MHz) δ 167.0, 160.2, 159.9, 139.0, 133.3,
132.3, 118.0, 108.6, 107.5, 106.4, 101.7, 70.3, 69.1, 52.5; MS (FD)
572.0 (MH+). Anal. Calc’d for C39H36O8: C, 71.31; H, 6.34.
Found: C, 71.17; H, 6.34.
3,5-Bis[3,5-bis(2-p r op en -1-oxy)ben zyloxy]ben zyl a lcoh ol
([G-2]-OH) (14). Prepared according to the general reduction
procedure using 650 mg (17 mmol) of LAH in 25 mL of THF
and 6.14 g (11 mmol) of ester 13 in 90 mL of THF to afford 5.5
g (94%) of 14 as a clear oil: 1H NMR (CDCl3, 400 MHz) δ 6.61
(d, 2H, J ) 2.4), 6.59 (d, 4H, J ) 2.4), 6.52 (t, 1H, J ) 2.2), 6.45
(t, 2H, J ) 2.2), 6.04 (ddt, 4H, J ) 17.2, 10.8, 5.2), 5.41 (ddt,
4H, J ) 17.2, 2.0, 1.2), 5.28 (ddt, 4H, J ) 10.4, 1.6, 1.4), 4.96 (s,
4H), 4.63 (s, 2H), 4.52 (ddt, 8H, J ) 5.2, 1.2); 13C NMR (CDCl3,
100 MHz) δ 160.3, 160.1, 143.7, 139.4, 133.3, 118.0, 106.3, 106.0,
101.6, 101.5, 70.2, 69.1, 65.5; MS (FD) m/z 544.3 (MH+).
3,5-Bis{3,5-bis[3,5-bis(2-pr open -1-oxy)ben zyloxy]-ben zyl-
oxy}-ben zyl a lcoh ol ([G-3]-OH) (16). Prepared according to
the general reduction procedure using 530 mg (14 mmol) of LAH
in 25 mL of THF and 9.20 g (8 mmol) of ester 15 in 75 mL of
THF to afford 8.95 g (100%) of a clear oil: 1H NMR (CDCl3, 400
MHz) δ 6.65 (d, 4H, J ) 2.2), 6.58 (d, 2H, J ) 2.2), 6.58 (d, 8H,
J ) 2.2), 6.54 (t, 2H, J ) 2.2), 6.51 (t, 1H, J ) 2.2), 6.44 (t, 4H,
J ) 2.2), 6.03 (ddt, 8H, J ) 17.2, 10.4, 5.2), 5.40 (ddt, 8H, J )
17.2, 1.6, 1.2), 5.27 (ddt, 8H, J ) 10.6, 1.6, 1.2), 4.97 (s, 4H),
4.96 (s, 8H), 4.62 (s, 2H), 4.51 (dt, 16H, J ) 5.2, 1.6); 13C NMR
(CDCl3, 100 MHz) δ 160.3, 160.2, 160.1, 143.7, 139.5, 139.3,
133.3, 118.0, 106.5, 106.4, 106.0, 101.8, 101.6, 101.4, 70.2, 70.1,
69.1, 65.4; MS (MALDI-TOF) m/z 1215.9 (M + Na+), 1231.9 (M
+ K+).
Cr oss-Lin k ed [G-3]-Den d r im er (7). To a solution of 91 mg
(24 µmol) of 6 in 1.0 L of benzene was added 11 mg (14 µmol) of
Grubbs catalyst (9). The mixture was stirred for 24 h and an
additional 8.5 mg (10 µmol) of Grubbs catalyst (9) was added.
After stirring for an additional 48 h, the solvent was removed
under reduced pressure. The crude mixture was purified with
column chromatography (silica gel, 7:3 PE/EtOAc (500 mL) and
19:1 CH2Cl2/EtOAc (1.0 L)). Cored dendrimer 7 was isolated from
the second solvent system as 79 mg (95%) of a white powder:
1H NMR (CDCl3, 500 MHz) δ 8.50-8.20 (bs, 3H), 6.80-6.10 (bs,
63H), 6.10-5.60 (bs, 24H), 5.20-4.60 (bs, 36H), 4.60-4.20 (bs,
48H); MS (MALDI-TOF) m/z 3420.7 (M + Na+ - 12C2H4), 3436.7
(M + K+ - 12C2H4), 3449.8 (M + Na+ - 11C2H4); SEC (THF)
Calc’d MW ) 1530.
Cor ed [G-3]-Den d r im er (8). To a solution of 46 mg (14 µmol)
of 7 in 1.0 mL of THF was added 31 mg (22 µmol) of K2CO3 and
500 µL (12 mmol) of MeOH. The mixture was stirred at 63 °C
for 24 h. The THF and MeOH were removed under reduced
pressure. To the resultant solution was added 10 mL of CH2Cl2
and 10 mL of water. The aqueous layer was extracted with CH2-
Cl2 (2 × 10 mL). The combined organic layers were washed with
10 mL of water, dried over Na2SO4, filtered and evaporated.
Column chromatography (silica gel, 3:2 PE/EtOAc (200 mL), 19:1
CH2Cl2/acetone (200 mL), and 9:1 CH2Cl2/acetone (500 mL))
provided 37 mg (83%) of a white powder: 1H NMR δ 6.60-6.20
(bs, 63H), 6.00-5.60 (bs, 24H), 5.15-4.95 (bs, 6H), 4.95-4.70
(bs, 36H), 4.70-4.20 (bs, 48H); MS (MALDI - TOF) m/z 3266.5
(M + Na+ - 12C2H4 - C9O3), 3282.3 (M + K+ - 12C2H4 - C9O3),
3292.0 (M + Na+ - 11C2H4 - C9O3), 3308.0 (M + K+ - 11C2H4
- C9O3); SEC (THF) Calc’d MW ) 1570.
Ack n ow led gm en t. Funding of this research by the
National Institutes of Health (GM61067) is gratefully
acknowledged.
Su p p or tin g In for m a tion Ava ila ble: Experimental de-
tails for preparing 6 and 15 and NMR and MALDI spectra for
selected compounds. This material is available free of charge
via the Internet at http://pubs.acs.org.
J O049368V
7366 J . Org. Chem., Vol. 69, No. 21, 2004