Synthesis of the Right Part of the Mycalamides
found 186.1240. To a stirred mixture of above diol (278 mg, 0.999
mmol), NMO (352 mg, 3.00 mmol), and activated molecular sieves
(0.5 g) in CH2Cl2 (10 mL) was added a catalytic amount of TPAP
(8.0 mg, 0.023 mmol) in one portion at room temperature. The
resulting deep blue solution was stirred at room temperature for
18 h. Upon consumption of the starting material, the reaction
mixture was filtered through a pad of silica gel, which was then
washed with CH2Cl2. The filtrate was concentrated in vacuo, and
the crude oil was purified by flash column chromatography (EtOAc/
hexane, 1:5) to afford bis-MOM lactone (176 mg, 61%) as a
colorless oil: 1H NMR (250 MHz, CDCl3) δ 6.02 (dd, J ) 17.6,
10.1 Hz, 1H), 5.11 (dd, J ) 17.6, 1.2 Hz, 1H), 5.06 (dd, J ) 10.1,
1.2 Hz, 1H), 4.97 (d, J ) 6.7 Hz, 1H), 4.68 (m, 3H), 4.36 (s, 3H),
3.43 (s, 3H), 3.41 (s, 3H), 1.21 (s, 3H), 1.20 (s, 3H); 13C NMR (63
MHz, CDCl3) δ 172.7, 143.1, 113.3, 96.4, 95.6, 86.6, 78.7, 74.8,
1112, 1039 cm-1; HRMS m/e calc’d for C28H41O5Br (M+)
536.2138, found 536.2186.
(4S,5S,6R)-5-Benzoyloxy-3,3-dimethyl-7-[(1,1-dimethylethyl)-
diphenylsilyl]oxy-4-methoxy-6-(trimethylsilyl)oxy-1-heptene (25).
To a stirred solution of BzCl (0.618 g, 4.40 mmol) and a catalytic
amount of DMAP (30 mg) in pyridine (5 mL) was added a solution
of alcohol 23 (1.131 g, 2.197 mmol) in pyridine (5 mL) dropwise
at room temperature. The resulting mixture was stirred at room
temperature for 6 h, diluted with diethyl ether (30 mL), and
quenched with H2O (30 mL). The separated aqueous layer was
extracted with ether (3 × 30 mL). The ether extracts were combined,
washed with saturated CuSO4 solution (30 mL), H2O (2 × 20 mL),
brine (30 mL), and dried over anhydrous Na2SO4. The solvent was
removed under reduced pressure, and the crude product was purified
by flash column chromatography (EtOAc/hexane, 1:20) to afford
ester 25 (1.299 g, 95%) as a colorless viscous oil: [R]23D -5.5° (c
56.3, 55.9, 39.5, 24.6, 23.4; IR (neat) 1787, 1153, 1108 cm-1
;
1
HRMS m/e calc’d for C13H22O6 (M+) 274.1416, found 274.1416.
A stirred solution of the above bis-MOM lactone (235 mg, 0.816
mmol) in CH2Cl2 (8 mL) was treated with solid BBr3‚Me2S (469
mg, 1.50 mmol) in one portion at 0 °C, and the mixture was stirred
at room temperature for 2 h. The reaction was quenched with
saturated NaHCO3 solution (20 mL) and extracted with Et2O (3 ×
15 mL). The combined Et2O phase was washed with brine (30 mL)
and dried over anhydrous Na2SO4. After removal of the solvent
under reduced pressure, the crude oil was purified by flash column
chromatography (EtOAc/hexane, 1:2) to afford dihydroxy lactone
14 (102 mg, 69%) as a colorless oil: 1H NMR (300 MHz, CDCl3)
δ 6.11 (dd, J ) 17.7, 10.9 Hz, 1H), 5.18 (dd, J ) 17.7, 1.0 Hz,
1H), 5.15 (dd, J ) 10.9, 1.0 Hz, 1H), 4.52 (m, 1H), 4.38 (m, 2H),
4.29 (br s, 1H), 3.28 (br s, 1H), 1.24 (s, 3H), 1.20 (s, 3H); 13C
NMR (63 MHz, CDCl3) δ 175.8, 143.0, 114.5, 87.1, 75.2, 73.8,
39.8, 24.7, 23.9; IR (neat) 3430, 1770, 1046 cm-1; HRMS m/e
calc’d for C9H14O4 (M+) 186.0892, found 186.0899.
Synthesis of Selenotetrahydrofuran 19. A stirred solution of
bis-MOM alkene 18 (1.610 g, 3.033 mmol) in CH2Cl2 (2 mL) was
treated with NPSP (1.813 g, 5.999 mmol) and CSA (0.139 g, 0.598
mmol) at room temperature, and the reaction was monitored by
TLC. Upon consumption of the starting material, the solvent was
removed under reduced pressure. The resulting yellow solid was
purified by flash column chromatography (EtOAc/hexane, 1:6) to
afford the desired product 19 (1.632 g, 85%) as a 1.12:1 mixture
of diastereomers: 1H NMR (250 MHz, CDCl3) δ 7.71 (m, 4H),
7.47 (m, 2H), 7.39 (m, 6H), 7.21 (m, 3H), 4.80 (m, 2H), 4.10 (dd,
J ) 8.7, 4.1 Hz, 0.45H), 4.32 (dd, J ) 8.1, 4.7 Hz, 0.55H), 3.95-
3.67 (m, 4H), 3.41 (s, 1.35H), 3.38 (s, 1.65H), 3.18 (m, 1H), 3.14
(s, 1.35H), 3.13 (s, 1.65H), 3.01-2.89 (m, 2H), 1.06 (m, 15H);
13C NMR (63 MHz, CDCl3) δ 135.8, 135.7, 133.5, 133.2, 132.3,
132.2, 131.3, 131.2, 129.7, 129.6, 129.0, 128.9, 127.7, 127.60,
126.59, 126.5, 96.4, 96.0, 90.5, 90.1, 86.2, 83.0, 80.1, 79.6, 77.3,
64.1, 64.0, 60.4, 60.2, 55.7, 55.6, 47.3, 46.7, 31.3, 27.8, 27.7, 26.8,
20.2, 19.2, 19.1, 17.8; IR (neat) 1105, 1030 cm-1; HRMS m/e calc’d
for C34H46O5SeSi (M+) 642.2279, found 642.2282.
Synthesis of Bromotetrahydrofuran 20. To a stirred solution
of bis-MOM alkene 18 (151 mg, 0.284 mmol) and propylene oxide
(0.5 mL) in CH2Cl2 (3 mL) was added NBS (0.054 g, 0.30 mmol)
at room temperature. The resulting mixture was stirred at room
temperature in the dark for 8 h. Upon consumption of the starting
material, the solvent was removed under reduced pressure, and the
crude yellow oil was purified by flash column chromatography
(EtOAc/hexane, 1:6) to afford the desired bromide 20 (130 mg,
86%, diastereomeric ratio >8:1) as a colorless oil: 1H NMR (250
MHz, CDCl3) δ 7.71 (m, 4H), 7.40 (m, 6H), 4.78 (dd, J ) 9.2, 6.8
Hz, 2H), 4.42 (dd, J ) 8.6, 4.0 Hz, 1H), 4.00 (dd, J ) 7.2, 5.4 Hz,
1H), 3.92 (m, 1H), 3.85 (m, 1H), 3.66 (d, J ) 4.3 Hz, 1H), 3.41 (s,
3H), 3.36 (m, 2H), 3.19 (m, 1H), 3.16 (s, 3H), 1.13 (s, 3H), 1.06
(s, 9H), 0.92 (s, 3H); 13C NMR (63 MHz, CDCl3) δ 135.7, 135.6,
133.5, 133.1, 129. 7, 129.6, 127.7, 127.6, 95.9, 90.8, 83.8, 79.7,
76.4, 63.9, 60.3, 55.5, 47.4, 31.1, 26.8, 19.9, 19.5, 19.2; IR (neat)
1.43, CHCl3); H NMR (400 MHz, CDCl3) δ 8.03 (m, 2H), 7.68
(m, 2H), 7.59 (m, 3H), 7.44 (m, 5H), 7.19 (m, 3H), 5.19 (dd, J )
17.7, 10.8 Hz, 1H), 5.40 (dd, J ) 5.5, 10.8 Hz, 1H), 4.91 (m, 2H),
3.97 (dd, J ) 11.0, 5.2 Hz, 1H), 3.76 (dd, J ) 10.5, 5.2 Hz, 1H),
3.36 (s, 3H), 3.27 (d, J ) 3.4 Hz, 1H), 1.06 (s, 3H), 1.03 (s, 12H),
0.06 (s, 9H); 13C NMR (63 MHz, CDCl3) δ 165.5, 145.09, 135.6,
135.5, 133.4, 133.1, 132.5, 130.7, 129.9, 129.7, 129.6, 129.5, 128.3,
128.2, 127.6, 127.5, 111.8, 84.9, 73.3, 72.5, 65.4, 61.5, 42.0, 26.7,
24.4, 23.3, 19.0, 0.26; IR (neat) 1725, 1112, 1027 cm-1; HRMS
m/e calc’d for C36H51O5Si2 (MH+) 619.3274, found 619.3267.
(4S,5S,6R)-5-Benzoyloxy-3,3-dimethyl-7-[(1,1-dimethylethyl)-
diphenylsilyl]oxy-6-hydroxy-4-methoxy-1-heptene (26). To a
stirred solution of benzoyl alkene 25 (1.088 g, 1.757 mmol) in
MeOH (10 mL) was added PPTS (44 mg, 0.18 mmol) at room
temperature, and the mixture was stirred at room temperature for
8 h. Upon consumption of the starting material, the reaction was
quenched with saturated NaHCO3 solution until gas evolution
ceased. The reaction mixture was extracted with ether (3 × 30 mL),
and the combined ether extracts were washed with brine (40 mL)
and dried over anhydrous Na2SO4. The solvent was removed under
reduced pressure, and the crude oil was purified by flash column
chromatography (EtOAc/hexane, 1:10) to afford alcohol 26 (0.784
g, 78.5%) as a colorless viscous oil: [R]23D -14.3° (c 1.08, CHCl3);
1H NMR (400 MHz, CDCl3) δ 8.04 (m, 2H), 7.66-7.59 (m, 4H),
7.54 (tt, J ) 1.3, 7.4 Hz, 1H), 7.43-7.33 (m, 6H), 7.31-7.27 (m,
2H), 5.94 (dd, J ) 10.8, 17.6 Hz, 1H), 5.50 (t, J ) 4.2 Hz, 1H),
4.93 (dd, J ) 1.2, 17.6 Hz, 1H), 4.85 (dd, J ) 1.2, 10.8 Hz, 1H),
3.95 (m, 1H), 3.68 (d, J ) 5.5 Hz, 2H), 3.41 (s, 3H), 3.19 (d, J )
4.1 Hz, 1H), 2.58 (br s, 1H), 1.08 (s, 3H), 1.05 (s, 3H), 1.04 (s,
9H); 13C NMR (63 MHz, CDCl3) δ 165.9, 144.9, 135.6, 135.5,
133.0, 132.82, 132.78, 130.3, 129.9, 129.8, 128.2, 127.74, 127.69,
111.7, 86.9, 72.34, 72.29, 64.6, 61.9, 41.9, 26.8, 24.5, 23.3, 19.1;
IR (neat) 3494, 1724 cm-1; HRMS m/e calc’d for C29H33O5Si (M+-
C4H9) 489.2097, found 489.2101.
(2R,3R,4S,6R)-6-(Bromomethyl)-2-((tert-butyldiphenylsilyloxy)-
methyl)-4-methoxy-5,5-dimethyltetrahydro-2H-pyran-3-yl Ben-
zoate (27). A stirred solution of hydroxy alkene 26 (0.594 g, 1.04
mmol) and propylene epoxide (1 mL) in DMF (5 mL) was treated
with solid NBS (0.374 g, 2.10 mmol) at room temperature. The
flask was shielded from light, and stirring was continued for 20 h.
Upon consumption of the starting material, the reaction mixture
was diluted with ether (50 mL) and washed with H2O (3 × 20
mL). The ether layer was washed with brine (20 mL) and dried
over anhydrous Na2SO4. The solvent was removed under reduced
pressure, and the residue was purified by flash column chroma-
tography (EtOAc/hexane, 1:10) to afford, as the major product,
bromide 27 (0.518 g, 77%) as a colorless oil: 1H NMR (250 MHz,
CDCl3) δ 8.01 (m, 2H), 7.70-7.07 (m, 13H), 5.26 (t, J ) 2.4 Hz,
1H), 4.13 (m, 1H), 3.89 (m, 1H), 3.80 (m, 1H), 3.57 (s, 3H), 3.48
(dd, J ) 10.8, 1.8 Hz, 1H), 3.32 (d, J ) 10.1 Hz, 1H), 3.13 (d, J
) 2.8 Hz, 1H), 1.04-0.97 (m, 15H); 13C NMR (63 MHz, CDCl3)
δ 165.7, 135.6, 135.5, 133.2, 133.1, 130.0, 129.7, 128.5, 127.7,
127.5, 83.4, 81.2, 75.1, 67.8, 61.9, 59.0, 38.0, 32.2, 26.8, 26.7, 23.3,
J. Org. Chem, Vol. 72, No. 2, 2007 395