Scheme 1
from unreacted 2 (17%); the order of chromatographic elution
mixture (NaH2PO4‚H2O and then methanolic HCl), filtration,
and removal of methanol in vacuo afforded a mixture of
products derived from hydroxy dienone 5. Silica gel chro-
matography of the mixture using 3:1 hexanes-EtOAc gave
pure trichodimerol (1) in 10% yield, [R]23D -351 (c ) 0.08
in CH3OH).12 The identities of synthetic 1 and natural
trichodimerol13 were confirmed by comparison of the 1H and
13C NMR, UV, IR, and mass spectra and TLC mobilities on
silica gel with three different solvent systems.
using 4:1 hexanes-EtOAc was 2 then 4 then 3.10
The structures of 3 and 4 were established by HMQC11a
and HMBC11b NMR analysis of one-, two-, and three-bond
1H-13C couplings. Racemic 3 was resolved chromatographi-
cally on a Daicel (Chiral Technologies) AD column using
5:15:80 CH3OH-i-PrOH-hexanes containing 0.1% CF3-
CO2H; the order of elution was first (S)-3, [R]23 -606 (c
D
) 0.9 in CH3OH), and then (R)-3, [R]23 +615 (c ) 1.0 in
D
CH3OH). Cleavage of the acetoxy dienone (S)-3 to the
corresponding hydroxy dienone (S)-5 was effected by treat-
ment with 10 equiv of sodium methoxide in methanol (0.015
M) at 23 °C for 6 h. Careful neutralization of the reaction
The remarkable spontaneous assembly of the complicated
pentacyclic system of 1 from the hydroxy dienone 5 can be
explained mechanistically by the following stepwise sequence
of events: (1) intermolecular Michael addition of the
nucleophilic CR of (S)-5 to Cδ of a second molecule of (S)-
5, (2) a second (intramolecular) Michael addition forming a
head-to-tail [4 + 4] cycloaddition dimer of 5, and (3) a
sequence of two hemiketal-forming ring closures by intra-
molecular addition of hydroxyl to keto carbonyl. The yield
reported above for this interesting dimerization has not been
optimized and may be subject to considerable improvement.
Research is underway on this point and also to develop an
enantioselective version of the reaction 2 f 3.
(10) A solution of sorbicillin (2) (0.5021 g, 2.16 mmol) in acetic acid
(50 mL) and CH2Cl2 (10 mL) at 23 °C was treated with lead tetraacetate
(1.1606 g, 2.62 mmol). The resulting solution was stirred for 30 min. After
addition of water the product was isolated by extraction with CH2Cl2. The
combined organic layers were dried over Na2SO4 and concentrated to a
residue which was chromatographed (1:4 to 1:2 EtOAc-hexanes gradient
elution, 500 mL of silica gel) to give 3 (0.2390 g, 38%) as a yellow
crystalline solid 4 (0.2202 g, 35%) as a yellow oil and 2 as a solid (85.5
mg, 17%). Found for 3: mp 110-111 °C; FTIR (film) 2935, 1738, 1651,
1556, 1372, 1244, 1072, 1019 cm-1; UV (MeOH) νmax nm (log ꢀ) 286
(3.99), 218 (3, 97); 1H NMR (500 MHz, CDCl3) δ 11.89 (s, 1H), 7.45 (dd,
1H, J ) 14.8, 10.8 Hz), 7.25 (s, 1H), 6.66 (d, 1H, J ) 14.8 Hz), 6.37 (m,
1H), 6.30 (m, 1H), 2.13 (s, 3H), 1.91 (d, 3H, J ) 5.8 Hz), 1.84 (s, 3H),
1.48 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 194.9, 193.2, 169.9, 162.5,
151.8, 148.3, 144.8, 130.0, 125.4, 120.1, 111.6, 78.1, 24.0, 20.4, 19.1, 7.1;
HRMS (EI) for C16H18O5 [M]+, m/z calcd 290.1154, found 290.1155. Found
for 4: FTIR (film) 2931, 1739, 1679, 1607, 1537, 1377, 1248, 1080, 1029,
996, 950, 936, 881 cm-1; UV (MeOH) νmax nm (log ꢀ) 404 (3.98), 298
(4.01), 262 (3.86), 210 (3.98); 1H NMR (400 MHz, CDCl3) δ 15.06 (s,
1H), 7.41 (dd, 1H, J ) 14.7, 10.3 Hz), 7.36 (s, 1H), 6.45 (d, 1H, J ) 14.7
Hz), 6.33-6.26 (m, 2H), 2.18 (s, 3H), 1.97 (s, 3H), 1.92 (d, 3H, J ) 5.9
Hz), 1.53 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 200.4, 194.5, 173.6,
169.9, 144.1, 141.7, 136.2, 130.8, 124.7, 117.2, 105.5, 82.9, 23.4, 20.1,
19.0, 16.0; HRMS (EI) for C16H18O5 [M]+, m/z calcd 290.1154, found
290.1157.
Acknowledgment. This research was assisted by graduate
fellowships to D.B.-S. from the National Science Foundation
and the Eli Lilly Co. and a research grant from the National
Science Foundation. We are grateful to Dr. He Xia for expert
assistance with HPLC separations.
OL991070H
(12) Reported: [R]D -376 (c ) 0.3 in CH3OH).1 The absolute config-
uration of 1 had been assigned using the exciton chirality method.1
(13) We are grateful to Prof. W. A. Ayer of the University of Alberta
for generously providing a sample of natural trichodimerol.
(11) (a) Mu¨ller, L. J. Am. Chem. Soc. 1979, 101, 4481. (b) Bax, A.;
Summers, M. F. J. Am. Chem. Soc. 1986, 108, 2093.
1504
Org. Lett., Vol. 1, No. 9, 1999