534
P. O. Gallagher et al. / Tetrahedron Letters 43 (2002) 531–535
16. For synthetic approaches to g-amino-b-hydroxy acids,
of 4.7 Hz requires that either the CH3 group (attached
to C-9) or the CH2CO moiety (C-12) is axial. The CH3
group (attached at C-9) is confirmed as equatorial,
because there is an NOE between CH3 (C-10) and the
H-12 proton pair. (Not shown on 2.) Sub-structure 3
extends from C-19 to C-40 and the CH3-doublet (C-24)
(l 0.78) provided an unambiguous starting point for
the spectral assignments. In the truncated spiroacetal
moiety 3, an NOE links H-22 (l 3.12) and H-31 (l
3.42), requiring the (E,E) configured arrangement 3
with the alkyl appendages at C-22 and C-31 equatori-
ally oriented. Furthermore, H-22 appears as a triplet of
doublets (2×9.8 Hz; 2.3 Hz) which is consistent with an
axial–axial coupling to H-23, as is the NOE correlation
between H-22 (confirmed as axially oriented) and the
(C-24) methyl group.
see: Poncet, J.; Jouin, P. Trends Org. Chem. 1998, 7,
123.
17. Evans, D. A.; Bartroli, J.; Shih, V. J. Am. Chem. Soc.
1981, 2127.
18. There are two diastereomeric syn isomers (at the car-
bons bearing the methyl and OR1 groups) because of
the chirality of the auxiliary. After auxiliary removal,
the syn isomers are enantiomeric. This follows from the
NMR identity with 20a, and the smaller, but opposite
sign of rotation ([h]2D5 −3.8 (c 0.68, CHCl3)) as expected
for a 2.5:1 ratio of syn aldols, with 20a now the minor
form.
19. (a) Wilson, S. R.; Guazzaroni, M. E. J. Org. Chem.
1987, 54, 3087; (b) for asymmetric crotylation, see:
Brown, H. C.; Randad, R. S. Tetrahedron 1990, 46,
4457.
8. Solladie´, G.; Bauder, C.; Biard, J.-F. Tetrahedron Lett.
2000, 41, 7747 reported the stereoselective reduction at
C4 of bistramide A and correlated the C4 alcohols with
bistramide D, which was concluded to be (R)-
configured at C4. Their other stereochemical sugges-
tions agree with ours.
9. For example, in isomer 10, H-6 has vic-couplings to
H-7ax and H-7eq of 10.9 and 5.4 Hz, requiring H-6 to
be axial and the enone grouping to be equatorial. Simi-
larly J11–9 of 4.8 Hz requires either the C-10 methyl
group or the C-11 ester group to be axial, and the
other equatorial. The chemical shifts of the methyl
group C-10 (l 16.5) and of C-12 (l 33.0) require these
groups to be equatorial and axial, respectively, with the
latter orientation inducing the higher field shift for C-6
(l 66.9) (g-effect).
20. Krapcho, A. P.; Larson, J. R.; Eldridge, J. M. J. Org.
Chem. 1977, 42, 3749.
21. We are grateful to Dr. Paul Bernhardt for this X-ray
analysis.
22. Bistramides A–D and K have been described4 as amor-
phous solids and dextrorotatory, with specific rotations
(CH2Cl2 solution) of 10° for A, B and C, 8° for D and
20° for K.
23. Characterisation data for selected compounds: Com-
pound 5: HREIMS: calcd for C15H22S2O2, 298.10557;
measured, 298.10526. Compound 9: calcd for C12H23O4
(M+H), 231.15780; measured, 231.15840. Compound
10: calcd for C15H24O4, 268.16557; measured,
268.16595, (NMR data for 10 is in Table 1). Com-
pound 12: calcd for C10H18O, 154.1357; measured,
154.1356. Compound 13: calcd for C12H20O3, 212.1412;
measured, 212.1418. Spiroacetal 16: for C12H22O3 calcd
C, 67.3; H, 10.3. Found C, 67.0; H, 10.6. [h]2D5 +64.0 (c
0.4, pentane). MS: 214 (7, M+), 183 (57), 154 (11), 142
(29), 127 (38), 115 (78), 112 (100), 97 (45), 84 (48), 55
(90), 43 (86). 1H NMR: (CDCl3) 3.72 (1H, HA of
ABX, dd, 11.5, 2.5), 3.67 (1H, dqd, 11.5, 6.5, 2.0), 3.52
(1H, HB of ABX, dd, 11.5, 7.5), 3.32 (1H, ddd, 10.0,
7.5, 2.5), 1.80 (1H, qt, 13.0, 4.5), 1.73–1.12 (10H, m),
1.11 (3H, d, 6.5), 0.88–0.85 (1H, m), 0.83 (3H, d, 6.5).
13C NMR: (CDCl3) 17.2 (CH3), 19.1 (CH2), 21.8
(CH3), 27.4 (CH2), 31.1 (CH), 32.5 (CH2), 35.8 (CH2),
35.9 (CH2), 63.3 (CH), 64.0 (CH2), 74.7 (CH), 95.8 (C);
spiroacetal 17: for C14H26O3 calcd 242.1882; measured
242.1885 [h]2D5 +61.6 (c 0.17, CHCl3) MS: 242 (1, M+),
224 (2), 154 (33), 115 (19), 112 (100), 97 (13), 83 (11),
71 (7), 67 (7), 55 (21), 43 (21), 41 (20). 1H NMR:
(CDCl3) 3.70–3.59 (3H, m), 3.21 (1H, td, 9.8, 2.6),
1.89–1.74 (3H, m), 1.63–1.23 (13H, m), 1.11 (3H, d,
6.3), 0.81 (3H, d, 6.5). (C6D6) 3.73 (1H, dqd, 11.3, 6.2,
2.2), 3.50 (2H, dt, 6.2, 2.3), 3.30 (1H, td, 9.4, 2.6), 1.98
(1H, qt, 13.6, 4.1), 1.86–1.48 (14H, m), 1.14 (3H, d,
6.0), 1.13–1.05 (1H, m), 0.71 (3H, d, 6.4). 13C NMR:
(CDCl3) 96.0 (C), 74.4 (CH), 65.3 (CH), 63.3 (CH2),
36.1 (CH2), 35.6 (CH2), 34.4 (CH2), 32.7 (CH2), 29.5
(CH2), 28.5 (CH2), 27.8 (CH2), 21.8 (CH3), 19.1 (CH2),
17.8 (CH3). Aldol 19: for C19H22O6N2 calcd C, 60.96;
H, 5.88; found C, 60.71; H, 6.08. [M+1]+ C19H23O6N2
calcd 375.1558, measured 375.1564. 1H NMR: (CDCl3)
0.84–0.90 (6H, d, 7.0), 1.35 (3H, d, 7.0), 2.29 (1H, m),
3.75 (1H, m), 3.74–3.97 (2H, ABX, 14.5, 6.5, 4.0), 4.18
10. (a) Frick, J. A.; Klassen, J. B.; Bathe, A.; Abraham-
sons, J. M.; Rappoport, H. Synthesis 1992, 621; (b)
Zhang, H.; Fletcher, M. T.; Avery, J. W.; Kitching, W.
Tetrahedron Lett. 1997, 38, 3477.
11. Banwell, M. G.; Bui, C. T.; Simpson, G. H. J. Chem.
Soc., Perkin Trans. 1 1998, 791.
12. (a) Enders, D.; Gatzweiler, W.; Dederichs, E. Tetra-
hedron 1990, 46, 4757; (b) Fletcher, M. T.; Kitching,
W. Chem. Rev. 1995, 95, 789.
13. Edmunds, A. J. F.; Trurb, W.; Oppolzer, W.; Cowley,
P. Tetrahedron 1997, 53, 2785.
14. Mesylation and reduction of alcohol 16 afforded a
single 2,3,8-trimethyl-1,7-dioxaspiro[5.5]undecane with
(2R,3S,6S,8R) stereochemistry and [h]2D2 68.8 (c 0.08,
CHCl3). NMR spectra matched those from the isomer
with [h]2D4 −69.4 (c 0.089, CHCl3), previously incorrectly
assigned as the (2S,3R,6S,8R) stereochemistry, because
the now verified NOE between H-2 and H-8 was not
detected. (Tu, Y. Q.; Hubener, A.; Zhang, H.; Moore,
C. J.; Fletcher, M. T.; Hayes, P.; Dettner, K.; McEr-
lean, C. S. P.; Kitching, W. Synthesis 2000, 1956.) In
this reference, the spiroacetal 40 should be 38, with
(2S,3R,6R,8S) stereochemistry. This correction estab-
lishes the stereochemical course of the reactions in
Schemes 3 and 4 of that reference.
15. The data for H-22 in bistramide A (l 3.12, td, J=9.8,
2.3 Hz) agrees well with the corresponding data for
spiroacetal 17 (l 3.21, td, 9.8 and 2.6 Hz), with one of
the large couplings (9.8 Hz) requiring both H-22 and
H-23 to be axial.