Synthesis of 10-Deoxymethynolide and Narbonolide
205.1, 175.3, 146.9, 125.8, 79.3, 73.4, 45.0, 44.2, 37.8, 34.2, 33.6,
26.8, 26.2, 25.1, 18.5, 18.4, 17.8, 17.2, 10.3, 9.5, -3.1, -3.3;
HRMS calcd for C23H42O4Si 410.2852, found 410.2863.
10-Deoxymethynolide (1). To a stirred solution of lactone 22
(11.0 mg, 0.0268 mmol) in dry THF (1 mL) at room temperature
was added TBAF (1.0 M in THF) (268 µL, 0.268 mmol) via a
syringe. After 2.5 h, the reaction mixture was concentrated.
Purification by flash chromatography on a silica gel column
(hexane:EtOAc ) 2:1) afforded 10-deoxymethynolide (1) (5.7 mg,
72%) as a colorless oil: [R]26.9D +94.1 (c 0.42, CHCl3); IR (film)
Hz, 1H), 6.07 (d, J ) 16.4 Hz, 1H), 6.81 (dd, J ) 16.3, 6.1 Hz,
1H), 6.89 (d, J ) 8.5 Hz, 2H), 7.20 (m, 2H); 13C NMR (75 MHz,
CDCl3) δ 204.3, 176.2, 159.3, 149.4, 130.1, 129.5, 126.9, 114.0,
84.1, 75.9, 71.7, 55.3, 43.8, 40.8, 39.3, 38.9, 37.3, 32.5, 29.7, 25.3,
17.0, 15.2, 15.0, 11.8, 10.4, 8.1; HRMS calcd for C28H42O6 [M +
Na]+ 497.2879, found 497.2874.
The alcohol (16.0 mg, 0.0337 mmol) prepared as described in
the previous procedure was dissolved in CH2Cl2 (3 mL). To this
solution was added Dess-Martin periodinane (DMP) (28.6 mg,
0.0674 mmol). The resulting solution was stirred for 30 min at room
temperature. After the reaction was completed, aqueous saturated
NaHCO3 (5 mL) was added and the mixture was extracted with
CH2Cl2 (3 × 5 mL). The organic layer was separated, dried
(MgSO4), and concentrated. Purification by flash chromatography
(hexane:EtOAc ) 7:1) offered the desired ketone 31 (13.2 mg, 83%)
ν
max 3479, 2966, 1724, 1627, 1457, 1376, 1326, 1276, 1172, 1083,
987, 894, 809, 736 cm-1; H NMR (300 MHz, CDCl3) δ 0.91 (t,
J ) 7.4 Hz, 3H), 1.0 (d, J ) 7.2 Hz, 3H), 1.12 (d, J ) 6.8 Hz,
3H), 1.22 (d, J ) 7.0 Hz, 3H), 1.30 (d, J ) 6.8 Hz, 3H), 1.2-1.37
(m, 2H), 1.47-1.78 (m, 4H), 2.46-2.66 (m, 3H), 3.56 (dd, J )
10.4 Hz, 1H), 5.00 (ddd, J ) 8.5, 5.5, 2.3 Hz, 1H), 6.42 (dd, J )
15.7, 1.1 Hz, 1H), 6.75 (dd, J ) 15.8, 5.4 Hz, 1H); 13C NMR (75
MHz, CDCl3) δ 204.9, 174.7, 147.1, 125.6, 78.2, 73.7, 45.1, 43.3,
38.0, 33.2, 25.1, 17.7, 17.4, 16.4, 10.3, 9.5; HRMS calcd for
C17H28O4 296.1988, found 296.1989.
1
as a colorless oil: [R]25.5 +83.1 (c 0.38, CH2Cl2); IR (film) νmax
D
2966.0, 1739.5, 1700.9, 1623.8, 1511.9, 1457.9, 1373.1, 1303.6,
1
1249.7, 1184.1, 1068.4, 987.4, 821.5, 736.7 cm-1; H NMR (300
MHz, CDCl3) δ 0.90 (t, J ) 7.3 Hz, 3H), 1.01 (d, J ) 6.6 Hz,
3H), 1.09 (t, J ) 7.4 Hz, 6H), 1.23 (m, 1H), 1.28 (d, J ) 7.5 Hz,
3H), 1.36 (d, J ) 7.0 Hz, 3H), 1.64-1.51 (m, 4H), 2.63 (m, 1H),
2.70 (m, 1H), 2.84 (dddd, J ) 7.3, 7.3, 7.3, 7.3 Hz, 1H), 3.80 (s,
3H), 3.82 (m, 1H), 3.90 (d, J ) 5.8 Hz, 1H) 4.49 (s, 2H), 4.94
(ddd, J ) 7.5, 7.5, 2.9 Hz, 1H), 6.30 (dd, J ) 15.8, 1.2 Hz, 1H),
6.74 (dd, J ) 15.8, 6.1 Hz, 1H), 6.88 (d, J ) 8.6 Hz, 2H), 7.28 (m,
2H); 13C NMR (75 MHz, CDCl3) δ 208.2, 203.1, 169.5, 159.2,
147.6, 130.7, 129.3, 126.9, 113.7, 79.5, 78.4, 73.7, 55.3, 50.7, 49.2,
43.0, 38.4, 35.8, 29.7, 23.2, 17.8, 16.0, 14.4, 13.8, 12.1, 10.5; HRMS
calcd for C28H40O6 472.2825, found 472.2823.
Narbonolide (2). To a solution of ketone 31 (7.7 mg, 0.016
mmol) in CH2Cl2:H2O [10:1 (v/v), 3 mL] was added dichlorodi-
cynoquinone (DDQ) (5.4 mg, 0.024 mmol) at 0 °C. The solution
was stirred for 2 h. After the reaction was completed, the solution
was filtered through a pad of Celite. The Celite pad was washed
with CH2Cl2 (3 × 10 mL). After the combined filtrate was
concentrated, purification by flash chromatography (hexane/EtOAc
) 2:1) provided the desired narbonolide (2) as a white solid (4.9
mg, 86%): mp 124.6-125.5 °C; [R]27.4D +68.7 (c 0.08, CH2Cl2);
IR (film) νmax 3475, 2927, 1735, 1627, 1457, 1376, 1257, 1187,
1099, 1022, 806 cm-1; 1H NMR (300 MHz, CDCl3) δ 0.93 (t, J )
7.3 Hz, 3H), 0.93 (d, J ) 7.3 Hz, 3H), 1.09 (d, J ) 6.8 Hz, 3H),
1.13 (d, J ) 7.0 Hz, 3H), 1.14 (d, J ) 6.9 Hz, 3H), 1.36 (d, J )
7.0 Hz, 3H), 3.04 (m, 1H), 3.71 (q, J) 7.1 Hz, 1H), 3.86 (q, J )
4.8 Hz, 1H), 5.15 (m, 1H), 6.10 (dd, J ) 16.3, 1.8 Hz, 1H), 6.91
(dd, J ) 16.3, 4.8 Hz, 1H); 13C NMR (75 MHz, CDCl3) δ 207.6,
205.1, 171.1, 148.5, 128.9, 78.0, 72.6, 50.2, 39.5, 38.8, 36.4, 34.9,
24.2, 18.6, 18.3, 14.3, 10.8, 10.6, 10.4; HRMS calcd for C20H32O5
352.2250, found 352.2248.
(E)-(3R,4S,5R,6S,7S,9R,13R,14R)-4-(tert-Butyldimethylsilany-
loxy)-14-ethyl-6-(4-methoxybenzyloxy)-3,5,7,9,13-pentamethy-
loxacyclotetradec-11-ene-2,10-dione (30). A flame-dried round-
bottomed flask was charged with vinyl ketone 29 (128 mg, 0.207
mmol) and CH2Cl2 (20 mL). Grubbs catalyst (second-generation)
(35.2 mg, 0.0414 mmol) was subsequently added as a solid,
producing a light brown solution that was stirred for 12 h at room
temperature. The mixture was then concentrated. Purification of
this residue by flash chromatography (hexane:EtOAc ) 5:1)
afforded the lactone 30 (108 mg, 88%) as a yellow liquid: [R]26.0
D
+28.9 (c 1.11, CHCl3); IR (film) νmax 2931, 1932, 1731, 1693,
1623, 1511, 1461, 1380, 1249, 1172, 1060, 833, 775 cm-1; 1H NMR
(300 MHz, CDCl3) δ 0.11 (d, J ) 17.7 Hz, 6H), 0.90 (m, 3H),
0.94 (s, 9H), 1.03 (d, J ) 7.0 Hz, 3H), 1.06 (d, J ) 7.0 Hz, 3H),
1.12 (m, 6H), 1.15(d, J ) 2.8 Hz, 3H), 1.33(m, 3H), 1.54 (m, 2H),
1.76 (m, 2H), 2.58 (m, 3H), 3.19 (d, J ) 9.3 Hz, 1H), 3.79 (m,
1H), 3.80 (s, 3H), 4.46 (ddd, J ) 10.5, 10.5, 10.5 Hz, 2H), 5.01
(ddd, J ) 7.2, 5.2, 1.9 Hz, 1H), 6.22 (dd, J ) 15.7, 1.8 Hz, 1H),
6.87 (d, J ) 8.6 Hz, 2H), 7.08 (dd, J ) 17.8, 4.6 Hz, 1H), 7.26 (d,
J ) 8.5 Hz, 2H); 13C NMR (75 MHz, CDCl3) δ 202.8, 176.4, 159.0,
150.0, 131.1, 129.0, 122.6, 113.7, 84.7, 76.1, 75.3, 72.2, 55.3, 45.1,
45.0, 44.9, 38.8, 34.7, 34.5, 26.3, 25.0, 19.0, 18.6, 17.7, 14.8, 10.5,
10.3, 9.1, -3.1, -3.8; HRMS calcd for C34H56O6Si [M + Na]+
611.3744, found 611.3741.
(E)-(3R,5R,6S,7S,9R,13R,14R)-14-Ethyl-6-(4-methoxybenzy-
loxy)-3,5,7,9,13-pentamethyloxacyclotetradec-11-ene-2,4,10-tri-
one (31). To a solution of lactone 30 (25.0 mg, 0.0424 mmol) and
CH3CN (1 mL) at room temperature was added a solution of [HF:
H2O:CH3CN (v/v/v) ) 1:0.5:8.5] (4 mL). After the mixture was
stirred for 17 h, it was neutralized with saturated NaHCO3 (10 mL)
and extracted with ether (3 × 10 mL). The combined organic
solution was washed with aqueous saturated NaCl (10 mL) then
dried (MgSO4) and concentrated. Purification by flash chromatog-
raphy (hexane:EtOAc ) 5:1) afforded the desired alcohol (16.0
Acknowledgment. This work was supported by the Korea
Research Foundation Grant (KRF-2004-015-C00267) and Center
for Molecular Design and Synthesis at KAIST. The authors are
grateful to Prof. David H. Sherman (University of Michigan)
for supplying the sample of narbonolide.
mg, 80%) as a colorless oil: [R]19.1 +28.1 (c 1.00, CHCl3); IR
D
Supporting Information Available: Experimental procedures
and characterization of compounds 10c, 11b-c, 15, 18-21, and
(film) νmax 3494, 2966, 1724, 1619, 1511, 1457, 1376, 1249, 1172,
1
1049, 983, 825 cm-1; H NMR (300 MHz, CDCl3) δ 0.91 (t, J )
1
23-29, and H NMR and 13C NMR spectra of compounds 1, 2,
7.4 Hz, 3H), 1.01 (m, 6H), 1.09 (m, 6H), 1.27 (d, J ) 6.6 Hz, 3H),
1.77-1.40 (m, 3H), 1.98 (m, 2H), 2.35 (m, 1H), 2.66(m, 4H), 3.55
(t, J ) 4.1 Hz, 1H), 3.76 (d, J ) 9.8 Hz, 1H), 3.81 (s, 3H), 4.47
(ddd, J ) 10.8, 10.8, 10.8 Hz, 2H), 5.14 (ddd, J ) 4.8, 3.2, 1.7
10c, 11b-c, 15, 18-22, and 23-31. This material is available free
JO702384D
J. Org. Chem, Vol. 73, No. 4, 2008 1461