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M. Hashimoto et al. / Tetrahedron 59 (2003) 3019–3040
Section 3.21.1 gave ethyl 2-[(2S,3S)-3,4-epoxy-2-(3-meth-
oxy-5-methyl-1-naphthoyl)-3-methylbutyryl]amino-2-[(S)-
5-hydroxymethylpyrilidin-2-ylidene]acetate (195 mg, 68%)
after silica gel column chromatography. IR (film): 3350,
2920, 1720, 1660, 1610, 1590, 1510, 1410, 1380, 1280,
1230, 1180, 1080, 1040, 700 cm21. The 1H NMR
spectrum of this sample showed that it consists of a
mixture of the two tautomers arising from its
enamine moiety (E/Z¼80:20). All the signals of the
major isomer and some of the minor isomer are
assigned. 1H NMR (400 MHz, CDCl3, carzinophilin
numbering, a¼0.80, b¼0.20): d 1.17 [3H£b, t, J¼7.1 Hz,
CH3CH2O (Z-isomer)], 1.20 [3H£a, s, J¼7.1 Hz,
CH3CH2O (E-isomer)], 1.58 (3H, s, C20H3), 1.76 [1H£a,
m, C12HH (E-isomer)], 1.89 [1H£b, m, C12HH
(Z-isomer)], 2.05 [1H£a, dq, J¼12.9, 8.0 Hz, C12HH
(E-isomer)], 2.15 [1H£b, m, C12HH (Z-isomer)], 2.69
(3H, s, C50CH3), 2.70 [2H£a, m, C13H2 (E-isomer)], 2.78
[1H£a, d, J¼4.6 Hz, C21HH (E-isomer)], 2.81 [1H£b, d,
J¼4.6 Hz, C21HH (Z-isomer)], 3.06 [1H£a, d, J¼4.6 Hz,
C21HH (E-isomer)], 3.13 [2H£b, m, C13H2 (Z-isomer)],
3.16 [1H£b, d, J¼4.6 Hz, C21HH (Z-isomer)], 3.42 [1H£b,
br, C11CHH (Z-isomer)], 3.53 [1H£a, dd, J¼5.9, 11.3 Hz,
C11CHH (E-isomer)], 3.59 [1H£b, br d, J¼11 Hz,
C11CHH (Z-isomer)], 3.70 [1H£a, dd, J¼3.9, 11.2 Hz,
C11CHH (E-isomer)], 3.86 [1H£b, m, C11H (Z-isomer)],
3.98 [1H£a, m, C11H (E-isomer)], 3.98 [3H£a, s, C30OCH3
(E-isomer)], 3.99 [3H£b, s, C30OCH3 (Z-isomer)], 4.10
[2H£a br q, J¼7.1 Hz, CH3CH2O (E-isomer)], 4.11 [2H£b,
br q, J¼7.1 Hz, CH3CH2O (Z-isomer)], 5.29 [1H£a, s,
C18H (E-isomer)], 5.32 [1H£b, s, C18H (Z-isomer)], 5.58
[1H£b, br s, NH (Z-isomer)], 6.96 [1H£a, br s, NH
(E-isomer)], 7.37 [2H, m, C60H, C70H], 7.42 (1H£b, br,
NH (Z-isomer)), 7.49 [1H£a, d, J¼2.6 Hz, C40H
(E-isomer)], 7.51 [1H£b, d, J¼2.6 Hz, C40H(Z-isomer)],
7.93 (1H, d, J¼2.6 Hz, C20H), 8.13 [1H£a, br, NH
(E-isomer)], 8.65 (1H, m, C80H). EI-MS (rel. int. %)
m/z¼512 (11, Mþ), 329 (15, [M2ArCO2]þ), 216 (52,
[ArCO2H]þ), 199 (100, ArCOþ). EI-HIMS. calcd for
C27H32O8N2 (Mþ): m/z¼512.2160; Found: m/z¼512.2173.
dq, J¼13.2, 7.5 Hz, C12HH (E-isomer)], 2.22 [1H£b, m,
C12HH (Z-isomer)], 2.69 (3H, s, C50CH3), 2.75 [2H£a, t,
J¼7.5 Hz, C13H2 (E-isomer)], 2.80 [1H£a, d, J¼4.6 Hz,
C21HH (E-isomer)], 2.81 [1H£b, not assignable, C21HH
(Z-isomer)], 3.04 [3H£a, s, CH3SO3 (E-isomer)], 3.05
[3H£b, s, CH3SO3 (Z-isomer)], 3.05 [1H£a, d, J¼4.6 Hz,
C21HH (E-isomer)], 3.14 [2H£b, m, C13H2 (Z-isomer)],
3.99 [3H£a, s, C30CH3 (E-isomer)], 4.00 [3H£b, s, C30CH3
(Z-isomer)], 4.05 [1H£a, dd, J¼6.7, 10.2 Hz, C11CHHO
(E-isomer)], 4.11 (2H br q, J¼7.1 Hz, CH3CH2O), 4.17
(1H, m, C11H), 4.26 [1H£a, dd, J¼3.9, 10.2 Hz, C11CHHO
(E-isomer)], 5.26 [1H£a, s, C18H (E-isomer)], 5.32
[1H£b, s, C18H (Z-isomer)], 5.97 [1H£b, br s, NH
(Z-isomer)], 0 6.97 [1H£a, br s, NH (E-isomer)], 7.37
[2H, m, C6 H, C70H], 7.50 [1H£a, d, J¼2.6 Hz, C40H
(E-isomer)], 7.51 [1H£b, d, J¼2.7 Hz, C40H (Z-isomer)],
7.94 [1H£a, d, J¼2.6 Hz, C20H (E-isomer)], 7.96 [1H£
b, d, J¼2.7 Hz, C20H (Z-iso0mer)], 8.15 [1H£0.7, br, NH
(E-isomer)], 8.67 (1H, m, C8 H). EI-MS (rel. int. %): m/z¼
590 (9.9, Mþ), 494 (10, [M2MsOH]þ), 216 (100,
ArCO2Hþ), 199 (96, ArCOþ). EI-HIMS: calcd for
C28H34O10N2S (Mþ): m/z¼590.1935; Found: m/z¼
590.1913.
3.21.4. Mesylation giving ent-25. Treatments of ethyl 2-
[(2S,3S)-3,4-epoxy-2-(3-methoxy-5-methyl-1-naphthoyl)-
3-methylbutyryl]amino-2-[(S)-5-hydroxymethylpyrilidin-2-
ylidene]acetate (182 mg, 355 mmol) in the same manner as
described in Section 3.21.3 gave iso-26 (192 mg, 92%) after
silica gel column chromatography. IR (film): 3280, 2880,
1720, 1670, 1600, 1510, 1410, 1350, 1280, 1230, 1170,
1090, 1040, 950 cm21. The 1H NMR spectrum of this
sample showed that it consists of a mixture of the two
tautomers arising from its enamine moiety (E/Z¼85:15). All
the signals of the major isomer and some of the minor
1
isomer are assigned. H NMR (400 MHz, CDCl3, carzino-
philin numbering, a¼0.85, b¼0.15): d 1.15 [3H£b, t,
J¼7.1 Hz, CH3CH2O (Z-isomer)], 1.19 [3H£a, s, J¼7.1 Hz,
CH3CH2O (E-isomer)], 1.58 [3H£a, s, C20H3 (E-isomer)],
1.59 [3H£b, s, C20H3 (Z-isomer)], 1.76 [1H£a, ddt, J¼5.1,
1.2, 7.5 Hz, C12HH (E-isomer)], 2.16 [1H£a, dq, J¼13.2,
7.5 Hz, C12HH (E-isomer)], 2.22 [1H£b, m, C12HH
(Z-isomer)], 2.69 (3H, s, C50CH3), 2.75 [2H£a, t,
J¼7.5 Hz, C13H2 (E-isomer)], 2.80 [1H£a, d, J¼4.6 Hz,
C21HH (E-isomer)], 2.81 [1H£b, C21HH (Z-isomer)], 3.04
(3H£a, s, CH3SO3 (E-isomer)), 3.05 [3H, b, s, CH3SO3
(Z-isomer)], 3.05 [1H£a, d, J¼4.6 Hz, C21HH (E-isomer)],
3.14 [2H£b, m, C13H2 (Z-isomer)], 3.99 [3H£a, s,
C30OCH3 (E-isomer)], 4.00 [3H£b, s, C30OCH3
(Z-isomer)], 4.05 [1H£a, dd, J¼6.7, 10.2 Hz, C11CHHO
(E-isomer)], 4.11 (2H br q, J¼7.1 Hz, CH3CH2O), 4.17 (1H,
m, C11H), 4.26 [1H£a, dd, J¼3.9, 10.2 Hz, C11CHHO
(E-isomer)], 5.26 [1H£a, s, C18H (E-isomer)], 5.32 [1H£b,
s, C18H (Z-isomer)], 5.97 [1H£b, br s, NH (Z-isomer)], 6.97
[1H£a, br s, NH (E-isomer)], 7.37 (2H, m, C60H, C70H),
7.50 [1H£a, d, J¼2.6 Hz, C40H (E-isomer)], 7.51 [1H£b,0d,
J¼2.7 Hz, C40H(Z-isomer)], 7.94 [1H£a, d, J¼2.6 Hz, C2 H
(E-isomer)], 7.96 [1H£b, d, J¼2.7 Hz, C20H (Z-isomer)],
8.15 [1H£0.7, br, NH (E-isomer)], 8.67 (1H, m, C80H). EI-
MS (rel. int. %): m/z¼590 (1.1, Mþ), 494 (1.1,
[M2MsOH]þ), 216 (52, ArCO2Hþ), 199 (100, ArCOþ).
EI-HIMS: calcd for C28H34O10N2S (Mþ): m/z¼590.1935;
Found: m/z¼590.1936.
3.21.3. Mesylation giving 25. A solution of ethyl 2-
[(2S,3S)-3,4-epoxy-2-(3-methoxy-5-methyl-1-naphthoyl)-
3-methylbutyryl]amino-2-[(R)-5-hydroxymethylpyrilidin-
2-ylidene]acetate (197 mg, 384 mmol), MsCl (58.0 mg,
507 mmol), and Et3N (100 mg, 990 mmol) in CH2Cl2
(3.0 mL) was stirred at 788C for 1 h. The mixture was
poured into water and extracted with Et2O. The combined
extracts were, washed with brine, dried over MgSO4, then
concentrated in vacuo. Purification of the residue by silica
gel column chromatography (CHCl3/acetone¼85:15) gave
26 (201 mg, 89%) as an amorphous solid. IR (film): 3350,
2970, 2920, 1720, 1665, 1595, 1505, 1415, 1300, 1240,
1170, 1090, 1040, 950, 730, 520 cm21. The 1H NMR
spectrum of this sample showed that it consists of a mixture
of the two tautomers arising from its enamine moiety
(E/Z¼85:15). All the signals of the major isomer and some
of the minor isomer are assigned. 1H NMR (400 MHz,
CDCl3, carzinophilin numbering, a¼0.85, b¼0.15): d 1.15
[3H£b, t, J¼7.1 Hz, CH3CH2O (Z-isomer)], 1.19 [3H£a, s,
J¼7.1 Hz, CH3CH2O (E-isomer)], 1.58 [3H£a, s, C20H3
(E-isomer)], 1.59 [3H£b, s, C20H3 (Z-isomer)], 1.76 [1H£a,
ddt, J¼5.1, 1.2, 7.5 Hz, C12HH (E-isomer)], 2.16 [1H£a,