Synthetic studies directed toward amphidinol 2: elucidation of the relative configuration of the C1-C10 fragment

Article abstract of DOI:10.1016/j.tetlet.2008.08.035

Model compounds (11 and 12) for the C1-C10 tetrahydropyran fragment of amphidinol 2 were prepared from (2S)-benzyloxypropanal in 9 steps. The synthetic route relied on diastereoselective diene-aldehyde cycloaddition, stereoselective C-allylation, and reag

Full text of DOI:10.1016/j.tetlet.2008.08.035

Tetrahedron Letters 49 (2008) 6209–6211
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Tetrahedron Letters
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Synthetic studies directed toward amphidinol 2: elucidation of the relative
configuration of the C1–C10 fragment
*
Praveen Kommana, Seung Won Chung, William A. Donaldson
Department of Chemistry, Marquette University, PO Box 1881, Milwaukee WI 53201-1881, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
Model compounds (11 and 12) for the C1–C10 tetrahydropyran fragment of amphidinol 2 were prepared
from (2S)-benzyloxypropanal in 9 steps. The synthetic route relied on diastereoselective diene-aldehyde
cycloaddition, stereoselective C-allylation, and reagent based enantioselective aldehyde allylation. Com-
parison of the NMR spectra for models 11 and 12 with that for amphidinol 2 indicated that the C1–C10
segment of the natural product possesses the 2R*,4R*,6R*,7S*,8R*,10S* relative configuration.
Ó 2008 Elsevier Ltd. All rights reserved.
Received 2 June 2008
Revised 1 August 2008
Accepted 8 August 2008
Available online 14 August 2008
The amphidinols (AM) 1-15 are a series of polyene-polyol natu-
ral products isolated from cultured dinoflagellates Amphidinium
klebsii and Amphidinium carterae.1 The members of this family are
characterized by a common bis-pyran polyol segment (highlighted
in dashed box for AM2, Fig. 1); they differ with respect to the
hydrophobic and hydrophilic chains connected to this common
fragment. The amphidinols exhibit variable hemolytic activity as
well as antifungal activity against Aspergillus niger (EC50 = 7.3 nM
mined.3 For this reason, amphidinol 3 has attracted the greatest
synthetic interest, and numerous groups have prepared extended
fragments of this target.4
Amphidinol 2 (AM2) was isolated >10 years ago from cultures
of Amphidinium klebsii by Tachibana’s group.1b The atom connec-
tivity indicated in Figure 1 was assigned on the basis of extensive
1H and 13C NMR spectroscopy. While these authors did not propose
the stereochemistry of AM2 at that time, it now seems likely that
the C23–C51 segment of AM2 has the same relative and absolute
configurations as the C23–C51 segment of AM3, given the nearly
identical nature of the 13C NMR spectral data for these segments
and their similar biological origin. We herein report on synthetic
studies directed at elucidating the relative configuration of the
C1–C10 segment of AM2 (solid box, Fig. 1).
and 6 l
g/disk, respectively, for AM21b), and this activity is been
attributed to the ability of the amphidinols to increase membrane
permeability. It has recently been speculated that the common
fragment adopts a ‘hairpin’ conformation and that the nature of
the polyene chain affects the membrane affinity, while differences
in the hydrophilic polyol segments of the AMs influence the pore
size.2 Amphidinol 3 is the only member of this family for which
the complete relative and absolute configuration has been deter-
Tashibana and co-workers1b assigned the hydrogens at C6, C7,
C8 and C10 of the tetrahydropyran ring A as equatorial, equatorial,
3
axial and axial, respectively, on the basis of their JH–H couplings.
For the purposes of identifying the relative configuration of the
C1–C10 segment, we arbitrarily chose to prepare the tetrahydro-
pyran ring with 6R,7S,8R,10S diastereomer. Diastereoselective
Lewis acid-catalyzed cyclocondensation of 2(S)-benzyloxypropanal
(prepared from readily available ethyl (S)-lactate) with 1-methoxy-
3-(trimethylsiloxy)-1,3-butadiene afforded the known5 dihydro-
pyranone 1 (Scheme 1). Reduction of 1 gave the pseudoglycal 2.
OH
HO
OH
OH
38
C
45
49
OH
HO
O
H
H
H
B
HO
OH
O
H
OH
1
OH
OH
34
OH
OH
Oxidation of 2 with mCPBA in methanol6 gave the
5-deoxymannoside 3, which was protected as its dibenzyl ether 4
using NaH/benzyl bromide. Ionization of the -methoxy group
a-methyl
HO
Me
OH Me OH Me Me
OH Me OH OH
4
a
O
23
with trimethylsilyl triflate and subsequent nucleophilic attack
with allyltrimethylsilane proceeded to give the trans tetrahydropy-
ran 5.7 Johnson-Lemieux8 oxidation of 5 afforded aldehyde 6.
Addition of allyl Grignard to 6 gave a mixture of two diastereo-
meric alcohols (7/8), which were difficult to completely separate
(Scheme 2). Alternatively, reaction of 6 with allyl diisopino-
campheylborane9 (generated from (+)-(IPC)2BOMe under salt-free
conditions), followed by oxidative work-up, gave 7 as the exclusive
6
10
A
OH
HO
AM2
OH
Figure 1. Skeletal structure of amphidinol 2 (AM2).
* Corresponding author. Tel.: +1 414 288 7374; fax: +1 414 288 7066.
E-mail address: william.donaldson@marquette.edu (W. A. Donaldson).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.08.035

6210
P. Kommana et al. / Tetrahedron Letters 49 (2008) 6209–6211
MeO
OH
OH
OH
OH
OH
OBn
2
DIBAL
Et2O
H
OsO4
K3Fe(CN)6
K2CO3
OBn
Me
OH
O
O
S
OTMS
OR
OR
Me
4
S
pentane
H
H
H
H
–78o
OHC
O
1) MgBr2/THF
O
Me
Me
2,6-lutidine
6
10
7
2) CF3CO2H
1 (89%)
OBn
RO
RO
OR
OR
mCPBA
MeOH
OBn
TMS
H
H
H2
Pd(OAc)2
MeOH
9, R = Bn (22%)
10, R = Bn (19%)
O
MeO
RO
O
Me
Me
11, R = H (99%)
12, R = H (72%)
0 oC/24 h
TMSOTf
CH3CN/0 oC
Scheme 3.
OH
OR
2 (99%)
3, R = H (84%)
NaH (2)/BnBr (2)
THF/12 h
are based on their relative NMR spectral data.10 In particular, the
sum of the chemical shifts for C2 and C4 of 9 (d 72.0 + 72.8 =
144.8 ppm) is greater than that for 10 (d 69.7 + 70.0 =
139.7 ppm). Hoffmann observed that ‘the sum of the chemical
shifts of the two oxygen bearing carbon atoms . . . should be
numerically smaller for the threo-1,3-diols than for their erythro-
counterparts’.14 This difference was attributed to the presence of
an axial substituent in the chair-like hydrogen bonded conformers
of the erythro-diastereomer, and this empirical trend is docu-
mented in numerous cases.15
4, R = Bn (86%)
4
OsO4
NaIO4
2,6-lutidine
OBn
OHC
H
OBn
H
H
H
O
S
O
Me
Me
R
6
10
BnO
BnO
dioxane/H2O (3:1)
RT, 12 h
OBn
5 (96%)
OBn
6 (60%)
Scheme 1.
Reductive debenzylation of 9 gave 11, while similar processing
of 10 gave 12 (Scheme 3). Notably, while the chemical shifts for
carbons C6–C12 of 11 and 12 are relatively similar, the chemical
shifts for C2 and C4 of 11 (d 72.0 and 69.7) are considerably differ-
ent than those for 12 (d 70.4 and 67.7 ppm). A comparison of the
13C NMR signals of 11 and 12, obtained in CD3OD/C5D5N/D2O, with
the literature values1b for the corresponding atoms in amphidinol 2
is graphically presented in Figure 2.
2
OH
OH
OBn
OBn
R
S
H
H
H
H
O
O
Me
Me
6
BnO
BnO
OBn
OBn
7
8
From these comparisons, the chemical shifts of C1–C7 of 12
have a better match with AM2, than do those of 11.16 Thus, we pro-
pose that the relative configuration of AM2 is 2R*,4R*,6R*,7S*,
8R*,10S*.17 The chemical shifts for C9 and C10 of both models 11
and 12 deviate from those of AM2 by >1 ppm. From the present
studies, it is not clear if these deviations are due to the differences
in molecular structure at C12 [–CH3 vs –CH2CH(Me)CH2 for AM2]
or due to a difference in the relative stereochemistry at C11 or
both. Further studies will be required to establish the relative con-
figuration at C11 as well as other stereocenters in the polyol chain
of AM2.
In summary, model compounds 11 and 12 for the C1–C12 seg-
ment of amphidinol 2 were prepared in 9 steps from (S)-2-benzyl-
oxypropanal. Comparison of the 13C NMR spectra of these models
with that for the corresponding segment of AM2 indicates that
the relative configuration of AM2 is 2R*,4R*,6R*,7S*,8R*,10S*.
THF/0 oC
(86%, 7 : 8 = 1:1)
(98%, 7 : 8 = 1:0)
BrMg
PhMe/–78 oC
PhMe/–78 oC
(dIPC)2B
(lIPC)2B
(93%, 7 : 8 = 1:2.4)
Scheme 2.
product.10 Homoallylic alcohol 7 was assigned the 4(R) stereo-
chemistry on the basis of the 1H NMR spectral data of the corre-
sponding (S)- and (R)- Mosher’s esters. In particular, the H-2
signal for the (S)-MTPA ester appears at d 5.62, while this signal
for the (R)-MTPA ester appears upfield at d 5.45 ppm.11 In contrast,
reaction of 6 with the chiral allylborane generated from (ꢀ)-(IPC)2-
BOMe, proceeded in a ‘mismatched’ double diastereoselective fash-
ion to give a mixture of 7 and 8 (1:2.4). Pure 810 could be prepared
from pure 7 by Mitsunobu inversion12 using p-nitrobenzoic acid,
followed by hydrolysis.
Table 1
1H NMR spectral data for AM1, 11 and 12 [chemical shift in d, solvent CD3OD/C5D5N/
The 13C NMR spectra of these two diastereomers are relatively
similar except for the signals for C4 and C6, which appear at d
72.1 and 76.1 ppm for 7 and d 68.0 and 71.7 ppm for 8, respec-
tively. The downfield shift for these signals in the syn- diastereo-
mer (7) compared to the anti-diastereomer (8) has previously
been observed in a number of diastereomeric tetrahydropyran
structures bearing an axial (2-hydroxyalkyl)- or (2-hydroxyalke-
nyl) substituent.13 Furthermore, the chemical shift for C6 of 7
(d 76.1 ppm) is a closer match with that for C6 of amphidinol 2
(d 77.3 ppm) than is the signal for C6 of 8 (d 71.7 ppm).
D2O (2:1:0.1)]
H
AM2a
11b
12b
1
10
2
3
30
4
5
50
6
7
8
3.57
3.59
4.05
1.66
1.67
4.14
1.68
2.00
4.27
3.72
4.00
3.55–3.63
3.55–3.63
3.93–4.03
1.64–1.75
1.64–1.75
4.08
1.64–1.75
1.93
4.26
3.57
3.57
4.06
1.60–1.71
1.60–1.72
4.15
1.60–1.71
1.96
4.25
3.66
3.99
3.67
3.93–4.03
With this insight, dihydroxylation of 7 with OsO4 proceeded in a
non-stereoselective fashion to afford a mixture of diols 9 and 10,
which were separable by preparative TLC (Scheme 3). The stereo-
chemical assignments for 9 and 10 (syn- and anti-, respectively)
a
Ref. 1b.
Present work.
b

P. Kommana et al. / Tetrahedron Letters 49 (2008) 6209–6211
6211
Δδ (AM2 – 11)
+2
+1
0
Δδ (AM2 – 12)
–1
–2
C1
C3
C5
C7
C9
C1
C3
C5
C7
C9
Figure 2. Difference between the chemical shifts of the carbon atoms of amphidinol 2 and those of models 11 and 12 (CD3OD/C5D5N/D2O).
15H); 13C NMR (75 MHz, CDCl3) d 16.0, 28.7, 35.3, 41.7, 68.0, 70.7, 71.68, 71.74,
71.8, 73.7, 74.1, 75.7, 76.5, 117.7, 127.6, 127.7, 127.8, 127.79, 127.88, 128.0,
128.45, 128.47, 128.48, 128.53, 135.1, 138.2, 138.7, 138.8. Compound 9: 1H
NMR (300 MHz, CDCl3) d 1.15 (d, J = 6.3 Hz, 3H), 1.38–1.49 (m, 2H), 1.63 (td,
J = 9.9, 14.4 Hz, 1H), 1.72–1.84 (m, 2H), 1.97 (td, J = 8.9, 13.0 Hz, 1H), 3.40 (t,
J = 3.3 Hz, 1H), 3.43 (dd, J = 5.4, 11.1 Hz, 1H), 3.56 (dd, J = 3.7, 11.1 Hz, 1H), 3.68
(dt, J = 3.5, 8.4 Hz, 1H), 3.76 (td, J = 3.6, 8.7 Hz, 1H), 3.81–3.91 (m, 2H), 4.06 (br
t, J = 9.9 Hz, 1H), 4.28 (br td, J = 3.0, 11.7 Hz, 1H), 4.49 (d, J = 11.1 Hz, 1H), 4.55
(s, 2H), 4.62 (d, J = 11.1 Hz, 1H), 4.66 (ABq, J = 12.3 Hz, 2H total), 7.23–7.40 (m,
15H); 13C NMR (75 MHz, CDCl3) d 15.7, 28.7, 36.7, 39.7, 66.6, 70.9, 71.6, 72.0,
72.1, 72.8, 73.4, 74.2, 75.7, 75.9, 76.8, 127.61, 127.63, 127.79, 127.81, 128.0,
128.1, 128.42, 128.44, 128.46, 128.48, 128.5, 128.54, 138.17, 138.24, 138.3.
Compound 10: 1H NMR (300 MHz, CDCl3) d 1.13 (d, J = 6.3 Hz, 3H), 1.42 (br d,
J = 14.7 Hz, 1H), 1.49–1.66 (m, 2H), 1.74–1.87 (m, 2H), 1.97 (td, J = 9.3, 12.8 Hz,
1H), 3.40 (t, J = 3.6 Hz, 1H), 3.44 (dd, J = 6.9, 10.8 Hz, 1H), 3.53 (dd, J = 3.6,
10.8 Hz, 1H), 3.69 (dt, J = 3.3, 8.3 Hz, 1H), 3.74–3.92 (m, 3H), 4.09 (dt, J = 3.0,
8.3 Hz, 1H), 4.28 (br d, J = 12.0 Hz, 1H), 4.52 (d, J = 11.7 Hz, 1H), 4.55 (s, 2H),
4.61 (d, J = 11.7 Hz, 1H), 4.66 (ABq, J = 12.3 Hz, 2H total), 7.22–7.40 (m, 15H);
13C NMR (75 MHz, CDCl3) d 15.8, 28.7, 36.2, 39.4, 66.8, 69.7, 70.0, 70.9, 71.7,
72.0, 73.5, 74.2, 75.85, 75.9, 127.6, 127.7, 127.8, 127.9, 128.1, 128.4, 128.5,
128.6, 138.3, 138.4. Compound 11: 1H NMR (400 MHz, CD3OD/C5D5N/
D2O = 2.0:1.0:0.1) d 1.13 (d, J = 6.4 Hz, 3H), 1.64–1.75 (m, 3H), 1.80–1.97 (m,
3H), 3.51 (ddd, J = 3.2, 6.5, 9.6 Hz, 1H), 3.55–3.63 (m, 2H), 3.67 (br s, 1H), 3.83
(pent, J = 6.4 Hz, 1H), 3.93–4.03 (m, 2H), 4.05–4.12 (m, 1H), 4.23–4.29 (m, 1H);
13C NMR (100 MHz, CD3OD/C5D5N/D2O = 2.0:1.0:0.1) d 19.6, 32.0, 37.9, 41.0,
67.3, 67.4, 69.7, 70.3, 71.8, 72.0, 75.5, 76.9. Compound 12: 1H NMR (400 MHz,
CD3OD/C5H5N/D2O) d 1.12 (d, J = 6.4 Hz, 3H), 1.60–1.71 (m, 4H), 1.82 (td,
J = 10.0, 12.8 Hz, 1H), 1.96 (ddd, J = 7.4, 9.4, 14.2 Hz, 1H), 3.51 (ddd, J = 3.2, 6.5,
9.7 Hz, 1H), 3.57 (d, J = 6.0 Hz, 2H), 3.66 (t, J = 2.8 Hz, 1H), 3.83 (pent, J = 6.4 Hz,
1H), 3.96–4.06 (m, 2H), 4.15 (pent, J = 6.2 Hz, 1H), 4.22–4.27 (m, 1H); 13C NMR
(100 MHz, CD3OD/C5D5N/D2O = 2.0:1.0:0.1) d 19.5, 32.0, 38.5, 41.7, 67.4, 67.7,
68.0, 70.3, 70.4, 71.8, 75.5, 77.0.
Acknowledgments
This work was supported by Marquette University through the
Wehr Professor Funds and partially supported by NSF (CHE-
0415771) and by NSF instrumentation Grant (CHE-0521323).
High-resolution mass spectra were obtained at the University of
Nebraska-Center for Mass Spectrometry.
References and notes
1. (a) Satake, M.; Murata, M.; Yasumoto, T.; Fujita, T.; Naoki, H. J. Am. Chem. Soc.
1991, 113, 9859–9861; (b) Paul, G. K.; Matsumori, N.; Murata, M.; Tachibana, K.
Tetrahedron Lett. 1995, 36, 6279–6282; (c) Paul, G. K.; Matsumori, N.; Konoki, K.;
Murata, M.; Tachibana, K. Harmful and Toxic Algal Blooms, Intergovernmental
Oceanographic Commission of UNESCO 1996, pp 503–506.; (d) Paul, G. K.;
Matsumori, N.; Konoki, K.; Murata, M.; Tachibana, K. J. Mar. Biotechnol. 1997, 5,
124–128; (g) Echigoya, R.; Rhodes, L.; Oshima, Y.; Satake, M. Harmful Algae 2005,
4, 383–389; (h) Morsy, N.; Matsuoka, S.; Houdai, T.; Matsumori, N.; Adachi, S.;
Murata, M.; Iwashita, T.; Fujita, T. Tetrahedron 2005, 61, 8606–8610; (i) Morsy,
N.; Houdai, T.; Matsuoka, S.; Matsumori, N.; Adachi, S.; Oishi, T.; Murata, M.;
Isashita, T.; Fujita, T. Biorg. Med. Chem. 2006, 14, 6548–6554.
2. Houdai, T.; Matsuoka, S.; Morsy, N.; Matsumori, N.; Satakeb, M.; Murata, M.
Tetrahedron 2005, 61, 2795–2802.
3. Murata, M.; Matsuoka, S.; Matsumori, N.; Paul, G. K.; Tachibana, K. J. Am. Chem.
Soc. 1999, 121, 870–871.
4. (a) BouzBouz, S.; Cossy, J. Org. Lett. 2001, 3, 1451–1454; (b) Flamme, E. M.;
Roush, W. R. Org. Lett. 2005, 7, 1411–1414; (c) De Vicente, J.; Betzemeier, B.;
Rychnovsky, S. D. Org. Lett. 2005, 7, 1853–1856; (d) Paquette, L. A.; Chang, S.-K.
Org. Lett. 2005, 7, 3111–3114; (e) Hicks, J. D.; Flamme, E. M.; Roush, W. R. Org.
Lett. 2005, 7, 5509–5512; (f) Chang, S.-K.; Paquette, L. A. Synlett 2005, 2915–
2918; (g) Dubost, C.; Marko, I. E.; Bryans, J. Tetrahedron Lett. 2005, 46, 4005–
4009; (h) De Vicente, J.; Huckins, J.; Rychnovsky, S. D. Angew. Chem., Int. Ed.
2006, 45, 7258–7262; (i) Bedore, M. W.; Chang, S.-K.; Paquette, L. A. Org. Lett.
2007, 9, 513–516; (j) Huckins, J. R.; De Vicente, J.; Rychnovsky, S. D. Org. Lett.
2007, 9, 4757–4760; (k) Colobert, F.; Kreuzer, T.; Cossy, J.; Reymond, S.;
Tsuchiya, T.; Ferrie, L.; Marko, I. E.; Jourdain, P. Synlett 2007, 2351–2354; (l)
Hicks, J. D.; Roush, W. R. Org. Lett. 2008, 10, 681–684.
11. Dale, J. A.; Mosher, H. S. J. Am. Chem. Soc. 1973, 95, 512–519.
12. Mitsunobu, O. Synthesis 1981, 1–28.
13. (a) Goekjian, P. G.; Wu, T.-C.; Kishi, Y. J. Org. Chem. 1999, 56, 6412–6422; (b)
Wolbers, P.; Hoffmann, H. M. R. Tetrahedron 1999, 55, 1905–1914; (c) Greer, P.
B.; Donaldson, W. A. Tetrahedron 2002, 58, 6009–6018; (d) Lewis, A.; Stefanuti,
I.; Swain, S. A.; Smith, S. A.; Taylor, R. J. K. Org. Biomol. Chem. 2003, 1, 104–116;
(e) Van Orden, L. J.; Patterson, B. D.; Rychnovsky, S. D. J. Org. Chem. 2007, 72,
5784–5793.
5. Danishefsky, S. J.; Pearson, W. H.; Harvey, D. F.; Maring, C. J.; Springer, J. P. J. Am.
Chem. Soc. 1985, 107, 1256–1268.
6. Saleh, T.; Rousseau, G. Tetrahedron 2002, 58, 2891–2897.
7. (a) Lewis, M. D.; Cha, J. K.; Kishi, Y. J. Am. Chem. Soc. 1982, 104, 4976–4978; (b)
Paterson, I.; Cumming, J. G. Tetrahedron Lett. 1992, 33, 2847–2850; (c) Romero,
J. A. C.; Tabacco, S. A.; Woerpel, K. A. J. Am. Chem. Soc. 2000, 122, 168–169.
8. Pappo, R.; Allen, D. S., Jr.; Lemieux, R. U.; Johnson, W. S. J. Org. Chem. 1956, 21,
478–479.
14. Hoffmann, R. W.; Weidmann, U. Chem. Ber. 1985, 118, 3980–3992.
15. (a) Umarye, J. D.; Lessmann, T.; Garcia, A. B.; Mamane, V.; Sommer, S.;
Waldmann, H. Chem. Eur. J. 2007, 13, 3305–3319; (b) Shang, S.; Iwadare, H.;
Macks, D. E.; Ambrosini, L. M.; Tan, D. S. Org. Lett. 2007, 9, 1895–1898; (c)
Labeeuw, O.; Roxhe, C.; Pansavath, P.; Genet, J.-P. Org. Lett. 2007, 9, 105–108;
(d) Murga, J.; Garcia-Fortanet, J.; Carda, M.; Marco, J. A. J. Org. Chem. 2004, 69,
7277–7283; (e) Caggiano, L.; Fox, D. J.; House, D.; Jones, Z. A.; Kerr, F.; Warren,
S. J. Chem. Soc., Perkin Trans. 1 2002, 2634–2645; (f) Trieselmann, T.; Hoffmann,
R. W.; Menzel, K. Eur. J. Org. Chem. 2002, 1292–1304; (g) Wolberg, M.; Hummel,
W.; Muller, M. Chem. Eur. J. 2001, 7, 4562–4571; (h) Bell, P. T.; Dasgupta, B.;
Donaldson, W. A. J. Organomet. Chem. 1997, 538, 75–82; (i) Kikuzaki, H.;
Kobayashi, M.; Nakatani, N. Phytochemistry 1992, 31, 1783–1786; (j) Kikuzaki,
H.; Kobayashi, M.; Nakatani, N. Phytochemistry 1991, 30, 3647–3651; (k) Evans,
D. A.; Chapman, K. T.; Carreira, E. M. J. Am. Chem. Soc. 1988, 110, 3560–3578.
16. While the differences in the 1H NMR spectral data for 11 and 12 (Table 1) are
not as great as those for 13C NMR spectra, there is also a closer match between
12 and AM2 than between 11 and AM2, particularly for the alcohol methine
hydrogens H2 and H4.
9. (a) Brown, H. C.; Jadhav, P. K. J. Am. Chem. Soc. 1983, 105, 2092–2093; (b)
Racherla, U. W.; Brown, H. C. J. Org. Chem. 1991, 56, 401–404.
10. Selected spectral data: 7: 1H NMR (300 MHz, CDCl3) d 1.12 (d, J = 6.0 Hz, 3H),
1.49 (td, J = 2.1, 15.0 Hz, 1H), 1.64–1.81 (m, 2H), 1.99 (td, J = 9.3, 12.6 Hz, 1H),
2.10–2.32 (m, 2H), 3.43 (t, J = 3.0 Hz, 1H), 3.68–3.91 (m, 4H), 4.27 (td, J = 3.1,
11.7 Hz, 1H), 4.54 (m, 2H), 4.59 (s, 2H), 4.68 (ABq, J = 12.9 Hz, 2H), 5.04–5.10
(m, 2H), 5.82 (tdd, J = 7.2, 10.8, 16.8 Hz, 1H), 7.22–7.40 (m, 15H); 13C NMR
(75 MHz, CDCl3) d 16.0, 28.7, 35.3, 41.8, 68.0, 70.7, 71.68, 71.73, 71.79, 73.7,
74.1, 75.7, 76.1, 76.6, 117.7, 127.6, 127.7, 127.79, 127.83, 128.0, 128.1, 128.46,
128.5, 128.6, 135.3, 138.5, 138.7, 139.0. Compound 8: 1H NMR (300 MHz,
CDCl3) d 1.08 (d, J = 6.0 Hz, 3H), 1.31 (ddd, J = 3.8, 8.5, 14.6 Hz, 1H), 1.64–1.80
(m, 2H), 1.94 (td, J = 9.9, 12.8 Hz, 1H), 2.15 (t, J = 6.7 Hz, 2H), 3.39 (t, J = 3.0 Hz,
1H), 3.55 (ddd, J = 3.1, 6.7, 9.5 Hz, 1H), 3.64–3.77 (m, 3H), 4.32 (td, J = 3.5,
10.7 Hz, 1H), 4.44 (s, 2H), 4.48 (d, J = 11.5 Hz, 1H), 4.54 (d, J = 11.5 Hz, 1H), 4.59
(s, 2H), 4.96–5.04 (m, 2H), 5.66 (tdd, J = 7.2, 9.9, 17.2 Hz, 1H), 7.15–7.35 (m,
17. The solvent system [CD3OD/C5D5N/D2O (2:1:0.1)] used in our work is the same
as that used by Tachibana et al.1b for AM2. As a referee has noted, this solvent
mixture would disrupt intramolecular hydrogen bonding within these polyol
structures, and thus should be used with caution should be used when
comparing the NMR spectral data in this solvent to those obtained in CDCl3.