Characterization of an abeo-taxane: Brevifoliol and derivatives

Article abstract of DOI:10.1021/np0304565

Brevifoliol is a natural diterpene isolated from Taxus baccata Nutt. A series of brevifoliol 1 derivatives, 2-8 and 10, were prepared for characterization and semisynthesis purposes and included the introduction of acetyl, Troc, and TES groups at C-5 and C-13. Derivatives 16-20 of 5-acetylbrevifoliol 2 were obtained via esterification with cinnamic acid, with both 2S-(-)- and 2R-(+)-3-phenyllactic acid, and with N-benzoyl-(2′ R,3′S)-3′-phenylisoserine at C-13. Brevifoliol compounds 12, 13, and 15 with either 2S-(-)-phenyllactate moieties at C-5 and C-13 or an N-benzoyl-(2′R,3′S)-3′-phenylisoserinyl at C-13 were also prepared. An abeo-taxane structure for 1 was clearly defined from the ¹³C NMR analysis of the 5-acetyl-13-oxo derivative 8 and from the conversion of 1 into 10, a conformationally restrained compound having a C-13, C-15 oxygen bridge. The biological activity of each of these derivatives is being studied.

Full text of DOI:10.1021/np0304565

838
J . Nat. Prod. 2004, 67, 838-845
Ch a r a cter iza tion of a n a beo-Ta xa n e: Br evifoliol a n d Der iva tives
Steve Tremblay,† Chantal Soucy,‡ Neil Towers,§ Philip J . Gunning,§ and Livain Breau*,†
De´partement de Chimie, Universite´ du Que´bec a` Montre´al, C.P. 8888 Succ. Centre-Ville, Montre´al (PQ), Canada, H3C 3P8,
and Department of Botany, University of British Columbia, 6270 University Boulevard, Vancouver B.C., Canada, V6T 1Z4
Received October 16, 2003
Brevifoliol is a natural diterpene isolated from Taxus baccata Nutt. A series of brevifoliol 1 derivatives,
2-8 and 10, were prepared for characterization and semisynthesis purposes and included the introduction
of acetyl, Troc, and TES groups at C-5 and C-13. Derivatives 16-20 of 5-acetylbrevifoliol 2 were obtained
via esterification with cinnamic acid, with both 2S-(-)- and 2R-(+)-3-phenyllactic acid, and with N-benzoyl-
(2′R,3′S)-3′-phenylisoserine at C-13. Brevifoliol compounds 12, 13, and 15 with either 2S-(-)-phenyllactate
moieties at C-5 and C-13 or an N-benzoyl-(2′R,3′S)-3′-phenylisoserinyl at C-13 were also prepared. An
abeo-taxane structure for 1 was clearly defined from the 13C NMR analysis of the 5-acetyl-13-oxo derivative
8 and from the conversion of 1 into 10, a conformationally restrained compound having a C-13, C-15
oxygen bridge. The biological activity of each of these derivatives is being studied.
The diterpenoid paclitaxel (Taxol), originally isolated
from the bark of Taxus brevifolia,1 has stimulated intense
research efforts in recent years because of its remarkable
anticancer activity.2,3 Recently, a lot of attention has been
focused on the search for other members of the taxane
group4 that may be directly active or may serve as precur-
sors for the semisynthesis of other active analogues.5-7 The
following work describes a detailed characterization of
brevifoliol 1, a relatively abundant metabolite isolated from
Taxus brevifolia needles (up to 0.30%). We have also been
interested in the synthesis of brevifoliol derivatives for their
biological activity, that is, microtubule disassembly and
P-glycoprotein (P-gp) inhibition.
Brevifoliol had originally been proposed to have a taxa-
4(20),11-diene system, A, similar to that of taxol8 (Figure
1). Lewis9 then proposed a taxane structure, B, for brevi-
foliol, while, later, Georg10 and Appendino11 both revised
the structure to an 11(15f1)-abeo-taxa-4(20),11-diene
skeleton, 1. These assignments were based solely on 1D
and 2D NMR spectral data, and three key quaternary
signals (i.e., C-1, C-8, and C-15) were missassigned.9,10 11-
(15f1)-abeo-Taxanes are, in general, difficult to character-
ize by NMR spectroscopy since they shift between different
conformational isomers in solution.12 In fact, most of the
abeo-taxane structures reported in the literature needed
to be confirmed by X-ray crystallography.11-13
An X-ray crystal structure of 2 was obtained by one of
the present coauthors (C.S.).14 It showed an 11(15f1)-abeo-
taxane structure, but unfortunately, the crystals were
unstable and its structure was obtained only after replacing
the reflections measured during the first 30 h by a set of
data taken at the end. Thus, the possibility of a skeletal
rearrangement of brevifoliol to the 11(15f1)-abeo-taxane
structure during the isolation and/or acetylation or during
X-ray irradiation could not be ruled out. Indeed, there are
examples of such chemical rearrangements in the litera-
ture.15,16
tion of brevifoliol from such extracts. An updated spectral
characterization of brevifoliol, 1, is given in Tables S1 and
S2 (Supporting Information).
We began our investigation with the preparation of
various derivatives with substituents at C-5 and C-13
(Figure 1). These included the mono- and bisacetyl, mono-
and bis-2,2,2-trichloroethoxycarbonyl (Troc), and bis-triethyl-
silyl (TES) groups. Although 5-, 13-acetyl, and 5,13-bisacetyl-
brevifoliol, 2, 3, and 4,8,14 are known in the literature, they
have not been adequately characterized. The Troc protecting
group was introduced at C-5 with high selectivity by treat-
ment of brevifoliol with Troc-Cl at -25 °C. Reactions at
higher temperatures (i.e., 22 and 43 °C) afforded 5, along
with up to 27% of 5,13-bisTroc-brevifoliol 6. In these react-
ions, the corresponding 13-Troc derivative could not be iso-
lated. To our surprise, all attempts to prepare the 5-TES
derivative gave only low yields of a single product, 5,13-TES-
brevifoliol, 7. However, 7 was obtained in good yield when
3.5 equiv of TESCl was used. Attempts to prepare the
corresponding 5- and 13-FMOC (fluorenylmethyloxycarbo-
nyl) derivatives by treating 1 with an excess of FMOC-Cl
in pyridine resulted in the recovery of unreacted brevifoliol,
even when the reaction mixture was heated to 50 °C.
Similarly, the introduction of a benzyl group at C-13 of 5,
via the use of an excess of benzyl bromide in the presence
of a catalytic amount of n-Bu4NI and using dimethylamino
pyridine (DMAP) as the base in pyridine, met with failure
even when heated to 80 °C. All of these transformations
illustrate unprecedented chemical behavior for 1.
None of these derivatives afforded crystals suitable for
X-ray analysis. Nonetheless, we were able to fully charac-
terize all compounds synthesized. As mentioned above, 11-
(15f1)-abeo-taxoids generally undergo a slow equilibration
between two or more conformational isomers in solution,
a characteristic of this type of diterpenoid structure.12 Thus,
the typical 1H spectrum of an abeo-taxane usually displays
a broadening of most of the signals and includes the
appearance of many minor additional peaks.13 However,
the room-temperature 1H and 13C NMR spectra of 2, 3, and
5 were very similar to that of brevifoliol, 1, being charac-
terized by the same sharp, well-resolved first-order spectra
with chemical shifts, multiplicities, and NOE effects as
those of the taxanes. Also, a broad doublet for H-9 was
observed in all derivatives, and in the cases of 5,13-
disubstituted derivatives 4, 6, and 7, additional broad
peaks were noted for the protons assigned to H-5, -10, and
Resu lts a n d Discu ssion
An extract of the needles and twigs of T. brevifolia was
obtained as previously described.8 We optimized the isola-
* To whom all correspondence should be sent. E-mail: breau.livain@
uqam.ca. Tel: (514) 987-3000, ext 8788#. Fax: (514) 987-4054.
† Universite´ du Que´bec a` Montre´al.
‡ConjuChem, 225 President-Kennedy, Suite 3950, Montre´al (PQ), H2X
3Y8.
§University of British Columbia.
10.1021/np0304565 CCC: $27.50
© 2004 American Chemical Society and American Society of Pharmacognosy
Published on Web 04/27/2004

Characterization of an abeo-Taxane
J ournal of Natural Products, 2004, Vol. 67, No. 5 839
F igu r e 1. Proposed structures for brevifoliol and syntheses of C-5, C-13 derivatives 2-7.
F igu r e 2. Oxidation of 2 to the conjugated ketone 8 and reduction back to 2.
F igu r e 3. Conversion of brevifoliol 1 to the C-13, C-15 bridge ether compound 10.
-13. The line broadening of these signals is consistent with
an abeo-taxane structure for these derivatives.
structure. To verify that there had not been any skeletal
rearrangement of 2 induced by PCC, which is an acidic
reagent, another oxidation of 2 was carried out under
neutral conditions20 with tetrapropylammonium perruth-
enate (TPAP) and N-methylmorpholine N-oxide (NMO) as
catalyst and co-oxidant, respectively. This reaction provided
the same enone. Indeed, the reduction of enone 8 with
NaBH4 in EtOH produced 2 once again, thus ruling out
the possibility of rearrangement of the A ring.
In the HMBC spectrum of 2, the signals at δ 5.34 (s, H-5),
5.58 (dd, H-7), and 6.01 (d, H-9) were correlated to three
acetyl carbonyl signals at δ 169.8, 170.9, and 170.1, which
indicates that these acetyl groups are located at C-5, -7,
and -9. Unfortunately, in all cases, the HMBC spectra,
acquired at various evolution delays, did not show any key
correlations between H-10 and C-15 nor between H-10 and
C-1. Also, while a correlation between the signals for the
protons of Me-16 and Me-17 with the peak assigned to C-15
was observed, key correlations of these protons with the
resonances for the carbons at C-1 and C-11, usually
observed in taxane structures, were either absent or buried
within the background noise. Confronted with the persis-
tent uncertainty surrounding the analyses of the various
2D NMR data of compounds 1-7, we envisaged other
simple chemical transformations that would enable us to
establish a more clear-cut distinction between the 11-
(15f1)-abeo-taxane structure and that of the taxanes, that
is, between a five- and six-membered A ring, respectively.
To this end, we reasoned that oxidation of the hydroxyl
function at C-13 would convert the A ring into either a five-
or six-membered enone, which should be easy to differenti-
ate by 13C NMR spectroscopy. Pyridinium chlorochromate
(PCC) oxidation of 5-acetylbrevifoliol, 2, yielded ketone 8
(Figure 2), for which the room-temperature 1H and 13C
NMR spectra displayed many broad signals. The 13C NMR
spectrum was, nonetheless, quite informative. It is known
that the carbonyl of the five-membered A ring enone
typically resonates further downfield (δ 208-210)17,18 than
that of the corresponding six-membered A ring enone in
taxinines (δ 198-200).19 The 13C NMR spectrum of enone
8 showed a single peak at δ 207, which suggests a five-
membered enone and, thus, an 11(15f1)-abeo-taxane
Although quite useful, this method is limited to sub-
strates having only one free secondary hydroxyl (i.e., C-13).
Another transformation would place a leaving group at
C-13. In an abeo-taxane structure such as 9, the angular
tertiary C-15 hydroxyl group is well positioned to undergo
an intramolecular nucleophilic substitution to form a bridge
ether (Figure 3). Such a substitution reaction cannot take
place with a taxane-type structure, but it should be possible
to isolate derivatives substituted at C-5 and C-13. To our
delight, treatment of brevifoliol with tosyl chloride provided
1
a single new product, 10 (Figure 3). Both the H and 13C
NMR spectra displayed sharp, well-resolved lines at room
temperature, consistent with a conformationally fixed
structure. A FABMS showed a parent peak at 538 amu for
the [M]+ ion, which corresponds to a dehydrated brevifoliol.
The peak usually observed at δ 2.7 (OH at C-15) in 1 was
also absent in 10. The unusual shielding of the resonance
for H-9 (0.85 ppm) is indicative of a change of conformation
relative to 1.12 Furthermore, the 13C resonances of all the
carbons in ring A and those surrounding this ring were
either shielded by an average of 3.5 ppm (C-2, -9, -10, and
-12) or deshielded by 4.5 ppm on average (C-11, -13, -14,
and -15) relative to those of 1 (Table S2). Thus, the
conformational changes observed essentially affect ring A
and the connecting parts of ring B. Together, these results
are consistent with a substitution product having the

840 J ournal of Natural Products, 2004, Vol. 67, No. 5
Tremblay et al.
F igu r e 4. Synthesis of brevifoliol derivatives 12, 13, and 15-20.
F igu r e 5. Construction of an oxetane D ring on derivative 3.
bridge ether depicted for 10. This structure was unambigu-
ously confirmed by the detection of long-range correlations
between H-13 and C-1, C-11, in the HMBC spectrum. Such
correlations are not feasible for a taxane structure; there-
fore, brevifoliol has an 11(15f1)abeo-taxane structure. A
consideration of the optical rotations provides an interest-
ing side note since all known 13-R-hydroxylated 11(15f1)-
abeo-taxane structures reported12,15,21 had negative rota-
tions, while those derivatives having a C13-C15 oxygen
bridge (i.e., 13-â oxygenated derivatives such as 10) have
positive ones.12 The above findings agree with that reported
for an abeo-taxane product having also a C13-C15 bridge
ether which was isolated from Taxus x media Rehd. Cv
Hicksii.12
Having firmly established a five-membered A ring for
brevifoliol, 1, we set out to further modify its structure
in an attempt to enhance its biological activity profile.
Over the past 10 years structure-activity relationship
studies5-7,15,22 have revealed some structural elements that
seem to be essential for the antitumor activity of the
taxanes. More specifically, these elements include a C-13
phenylisoserine side chain, an oxetane D ring, a C-4 alkoxy
group, and a C-2 aromatic ester or cyclohexanoate moiety.
As for the inhibition of the drug transport activity of P-gp,
the most active taxoids have in common a C-5 cinnamoyl
moiety. The A ring could be five- or six-membered, and the
C-13 was either substituted with an acetyl group or was a
ketone.23
may be considered to be deaminated derivatives of phe-
nylisoserine or hydrated derivatives of the cinnamate
moiety) and the phenylisoserinate at the C-13 and C-5
positions. A subsequent objective was the construction of
an oxetane D ring.
Our first structural modification of brevifoliol, 1, was to
couple it to the propanoic acid (2S)-11a to give a mixture
of isomers 12 and 13 having a C-13 side chain and a free
C-5 hydroxyl group and vice versa (Figure 4). These
esterifications were carried out using the coupling agent
dipyridyl carbonate (2-DPC).24 An N-benzoyl-(2′R,3′S)-
phenylisoserine moiety was introduced at C-13 of 1 via
esterification of the corresponding O-tetrahydropyranyl
25
(THP)-protected acid 14, and subsequent hydrolysis of
the THP ether afforded the ester 15.26 5-Acetylbrevifoliol,
2, was coupled with cinnamic acid to provide ester 16. Both
phenyl lactate antipodal moieties were introduced at C-13
of 2, via esterification of the corresponding O-THP-
protected acids, (2S)-(-)-11a or (2R)-(+)-11b, and subse-
quent hydrolysis of the THP ether intermediate 17 pro-
duced the hydroxy ester derivatives 18 and 19. Only the
S-intermediate was isolated. An N-benzoyl-(2′R,3′S)-phe-
nylisoserine moiety was also introduced via esterification
of the corresponding acid, 14, with the hydroxyl at the C-13
of 2 to provide 20.
Our next goal was to place an oxetane D ring on the
brevifoliol skeleton. Several methods to accomplish this
transformation have been reported.7,27 A method developed
by Danishefsky’s group27c was applied to compound 3, but
this led to complete decomposition of the starting material
Our initial objective was the introduction of a lateral side
chain such as cinnamoyl, (R)- and (S)-phenyl lactate (which

Characterization of an abeo-Taxane
J ournal of Natural Products, 2004, Vol. 67, No. 5 841
0.090 mmol) solution in pyridine (1 mL) at -30 °C, containing
4 Å-ms (400 mg). The reaction mixture was stirred at -30 °C
for 2 h. More Troc-Cl (6.2 µL, 0.045 mmol) was added and
stirred for an additional hour at -30 °C. The same quantity
of Troc-Cl was added, and the mixture was kept at -20 °C for
a 15 h period. One last portion of Troc-Cl was added and
stirred at -20 °C for another 2 h. MeOH (50 µL) was then
added, and the reaction mixture was allowed to warm to room
temperature. The salts that formed were filtered through
Celite and washed with CH2Cl2 (4 mL) and EtOAc (4 mL), and
the filtrate was concentrated under reduced pressure. The
residue was purified by radial chromatography (2-5% EtOAc-
CH2Cl2), giving 0.1 mg (0.1%) of 5,13-bis(Troc)brevifoliol 6 and
44.4 mg (68%) of 5 followed by 21 mg of impure 1. The
derivative 5 was obtained as a white powder: mp 110-112
(Figure 5). To close the oxetane ring, we adapted Potier’s
protocol.7 Thus, osmylation of 3 was carried out with
N-methylmorpholine-N-oxide (NMO) and OsO4 to produce
the triol 21. We protected the primary alcohol function as
the tert-butyldimethylsilyl ether and then mesylated the
secondary alcohol. This gave 23, while subsequent removal
of the silane function with dry TBAF gave the free primary
alcohol 24. Further treatment of 24 with tetrabutylammo-
nium acetate produced the oxetane 25 (Figure 5).
We have prepared and characterized the C-5- and C-13-
acetyl, 1-4, Troc 5 and 6, and TES, 7, derivatives of
brevifoliol, 1. Two simple transformations (oxidation of the
C-13 allylic alcohol to give 8 and formation of a C13-C15
ether bridge to give 10) were used to unambiguously
differentiate the abeo-taxane-type substrate from that of
taxane. Spectroscopic data collected from 5-acetyl-13-
oxobrevifoliol, 8, and its ether, 10, clearly and definitively
established the structure of brevifoliol to be 9R,7â-diac-
etoxy-10â-benzoxy-11(15f1)-abeo-taxane-4(20),11-dien-
5R,13R,15-triol (1), in which ring A is five-membered.
Derivatives 12 and 13, having an S-(-)-3-phenyllactate at
C-5 and C-13 of brevifoliol, as well as brevifoliol-13-[N-
benzoyl-2′R, 3′S)-3′-phenylisoserinate], 15, were prepared.
Derivatives with a cinnamoyl (16), both S-(-)- and R-(+)-
3-phenyllactate (18, 19), and a [N-benzoyl-2′R,3′S)-3′-
phenylisoserinate] (20) esterified at the C-13 of 5-acetyl-
brevifoliol were also synthesized. We are currently evaluat-
ing these brevifoliol derivatives for microtubule assembly
activity and for P-gp inhibition, and the results will be
reported elsewhere.28
°C; [R]23 -35.0° (c 1.03, CH2Cl2); IR (KBr) νmax 3567, 2970,
D
1746, 1653, 1602, 1450, 1376, 1244, 1090, 1069, 1033, 904, 819,
784, 759, 712, 602, 572 cm-1 1H NMR (CDCl3, 500 MHz) δ
;
0.92 (3H, s, H-19), 1.02 (3H, s, H-16), 1.08 (1H, dd, J ) 14.3,
6.7 Hz, H-14R), 1.33 (3H, s, H-17), 1.40 [1H, s, OH (C-13)],
1.45 (1H, d, J ) 13.9 Hz, H-2R), 1.77 [3H, s, O2CCH3, (C-9 or
C-7)], 1.93 (1H, td, J ) 13.5, 3.9 Hz, H-6â), 2.07 [3H, s, O2CCH3
(C-9 or C-7)], 2.15 (3H, s, H-18), 2.18 (1H, dd, J ) 15.3, 5.2
Hz, H-6R), 2.44 (1H, dd, J ) 13.9, 8.9 Hz, H-2â), 2.52 (1H, dd,
J ) 14.3, 7.4 Hz, H-14â), 2.76 (1H, d, J ) 8.9 Hz, H-3R), 2.84
[1H, br s, OH (C-15)], 4.42 (1H, dd, J ) 7.4, 6.7 Hz, H-13â),
4.67, 4.86 (each 1H, d, J ) 11.7 Hz, CCl3CH2O), 4.99 (1H, s,
H-20a), 5.30 (1H, t, J ) 3.9 Hz, H-5â), 5.35 (1H, s, H-20b),
5.60 (1H, dd, J ) 11.0, 5.2 Hz, H-7R), 6.02 (1H, br d, J ) 10.3
Hz, H-9â), 6.62 (1H, d, J ) 10.3 Hz, H-10R), 7.43 (2H, t, J )
7.5 Hz, Hm-Ph), 7.55 (1H, t, J ) 7.5 Hz, Hp-Ph), 7.87 (2H, d, J
) 7.5 Hz, Ho-Ph); 13C NMR (CDCl3, 125 MHz) δ 11.8 (CH3,
C-18), 12.8 (CH3, C-19), 20.7 [CH3, O2CCH3 (C-9 or C-7)], 21.3
[CH3, O2CCH3 (C-7 or C-9)], 24.8 (CH3, C-17), 27.0 (CH3, C-16),
29.0 (CH2, C-2), 33.5 (CH2, C-6), 38.9 (CH, C-3), 44.7 (C, C-8),
48.1 (CH2, C-14), 63.2 (C, C-1), 69.2 (CH, C-7), 70.7 (CH, C-10),
75.4 (C, C-15), 76.7 (CH2, CH, CCl3CH2O and C-9), 77.6 (CH,
C-13), 80.0 (CH, C-5), 94.2 (C, CCl3C), 115.2 (CH2, C-20), 128.8
(CH, C-3′), 129.2 (C, C-1′), 129.4 (CH, C-2′), 133.3 (CH, C-4′),
134.2 (C, C-11), 144.5 (C, C-4), 151.8 (C, C-12), 152.6 (C,
CCl3CH2OCO2), 164.1 (C, O2CPh), 169.7 [C, O2CCH3 (C-9 or
C-7)], 169.8 [C, O2CCH3 (C-7 or C-9)]; FABMS (NBA) m/z 713
[MH - H2O]+, 609-615 [MH - PhCO2H]+, 591 [MH -
PhCO2H-H2O]+, 549-566 [MH - PhCO2H - AcOH]+, 533
[MH - PhCO2H - AcOH - H2O]+.
Exp er im en ta l Section
Gen er a l Exp er im en ta l P r oced u r es. 1H NMR spectra
were recorded using a 500, 300BB, or 200 MHz spectrometer
with either CD2Cl2 or CDCl3 as solvent. Chemical shifts are
reported in parts per million (δ) and are downfield from
(CH3)4Si. 13C spectra were recorded at 75 or 125 MHz. Optical
rotation data were recorded at 589 nm on a digital polarimeter.
Melting points are uncorrected. Mass spectra were obtained
using a VG Auto-SpecQ FAB+ Magnet BpI or a GC-MS (GCD
plus gas chromatography-electron ionization detector) equipped
with a 5% cross-linked PhMe silicone HP 19091 J -433 column,
and the mass data are reported as m/z, with the intensity
indicated in parentheses as a percent of the base peak. Silica
gel 60 (230-400 mesh) was used for all column chromatogra-
phy. Some separations were carried out on a centrifugally
accelerated, radial, thin-layer chromatograph (Chromatotron)
using silica gel PF-254 with CaSO4‚1/2H2O type 60 as adsor-
bent.
S-(-)- and R-(+)-3-phenyllactic acid, chlorotriethylsilane
(TESCl), 2,2,2-trichloroethyl chloroformate (TrocCl), TsCl,
DMAP, 4-methylmorpholine-N-oxide (NMO), tetrapropylam-
monium perruthenate(VII) (TPAP), imidazole, and S-(+)-
phenylglycine as well as all other inorganic reagents were used
without further purification. The isolation of brevifoliol, 1, from
T. brevifolia needles8 and the syntheses of compounds 2-4,
11a , and 11b are described in the Supporting Information
section. (2R,3S)-(-)-2-(Tetrahydropyran-2-yloxy)-3-phenyl-
methanamido)propanoic acid, 14, was prepared from S-(+)-
phenylglycine as previously described25 with the exception that
tetrahydropyranyl was used as a protecting group instead of
an ethoxyethyl group. Di-2-pyridyl carbonate (2-DPC) was
prepared as previously described.24 Pyridine and triethylamine
were freshly distilled over calcium hydride prior to use. Celite
was used as a filtering agent. THF and diethyl ether were
dried over sodium/benzophenone and distilled under a nitrogen
atmosphere immediately prior to use. All reactions were
carried out under nitrogen unless otherwise noted. Molecular
sieves (4 Å-ms) were crushed and flame dried prior to use.
5-Tr ocbr evifoliol (5). 2,2,2-Trichloroethoxycarbonyl Troc-
Cl (6.2 µL, 0.045 mmol) was added to a brevifoliol (1, 50 mg,
5,13-Bis(Tr oc)br evifoliol (6). Troc-Cl (12 µL, 0.087 mmol)
was added to a solution of 1 (26 mg, 0.047 mmol) in pyridine
(0.5 mL) containing 4 Å-ms (200 mg). The reaction mixture
was stirred at room temperature for 3 h. More Troc-Cl (12 µL,
0.087 mmol) was added, and the mixture was stirred for an
additional 15 h. The salts that formed were filtered through
Celite and washed with CH2Cl2 (2 mL) and EtOAc (2 mL), and
the filtrate was concentrated under reduced pressure. The
residue was purified by radial chromatography (2-5% EtOAc-
CH2Cl2), giving 15.4 mg (36%) of 6 and 16.4 mg (48%) of 5, as
white powders. The derivative 6 had the following physical
characteristics: mp 177-179 °C; [R]23D -17.0° (c 0.91, CH2Cl2);
IR (KBr) νmax 3578, 2976, 1752, 1663, 1600, 1438, 1374, 1248,
1132, 1090, 1067, 1033, 938, 920, 882, 822, 788, 714, 602, and
570 cm-1 1H NMR (CDCl3, 500 MHz) δ 0.94 (3H, s, H-19),
;
1.12 (3H, s, H-16), 1.35-1.45 (1H, m, H-14R), 1.38 (3H, s,
H-17), 1.53 (1H, d, J ) 14 Hz, H-2R), 1.76 (3H, s, O2CCH3,
C-9 or C-7), 1.95 (1H, td, J ) 14, 3.5 Hz, H-6â), 2.07 [3H, s,
O2CCH3 (C-7 or C-9)], 2.09 (3H, s, H-18), 2.20 (1H, dd, J ) 14,
4.2 Hz, H-6R), 2.45 (1H, dd, J ) 14, 9 Hz, H-2â), 2.54 (1H, dd,
J ) 13.9, 7.4 Hz, H-14â), 2.70 [1H, br s, OH (C-15)], 2.73 (1H,
d, J ) 9 Hz H-3R), 4.68 [1H, d, J ) 11.8 Hz, CCl3CH2O (C-5
or C-13)], 4.79 [2H, br dd, CCl3CH2O (C-5 or C-13)], 4.99 [2H,
br s, H-20a + CCl3CH2O (C-5 or C-13)], 5.27 (1H, t, J ) 3.5
Hz, H-5â), 5.38 (1H, s, H-20b), 5.53 (1H, br t, J ) 7.4 Hz,
H-13â), 5.65 (1H, dd, J ) 10, 4.2 Hz, H-7R), 6.15 (1H, br d, J
) 10.3 Hz, H-9â), 6.67 (1H, br d, J ) 10.3 Hz, H-10R), 7.45
(2H, t, J ) 7.5 Hz, Hm-Ph), 7.55 (1H, t, J ) 7.5 Hz, Hp-Ph), 7.88
(2H, d, J ) 7.5 Hz, Ho-Ph); 13C NMR (CDCl3, 75 MHz) δ 11.9
(CH3, C-18), 12.8 (CH3, C-19), 20.7 [CH3, O2CCH3 (C-9) or

842 J ournal of Natural Products, 2004, Vol. 67, No. 5
Tremblay et al.
(C-7)], 21.3 [CH3, O2CCH3 (C-7) or (C-9)], 25.1 (CH3, C-17), 27.2
(CH3, C-16), 29.3 (CH2, C-2), 33.7 (CH2, C-6), 38.4 (CH, C-3),
43.7 (CH2, C-14), 44.8 (C, C-8), 62.6 (C, C-1), 69.2 (CH, C-7),
69.5 (CH, C-10), 75.6 (C, C-15), 76.4 (CH2, Cl3CH2O), 76.7 [CH,
CH2, C-9 and Cl3CH2O], 79.2 (CH, C-5), 84.2 (CH, C-13), 94.5,
(C, CCl3C), 94.8 (C, CCl3C), 115.4 (CH2, C-20), 128.8 (CH, C-3′),
129.1 (C, C-1′), 129.5 (CH, C-2′), 133.4 (CH, C-4′), 136.9 (C,
C-11), 144.2 (C, C-4), 146.7 (C, C-12), 153.0 (C, CCl3CH2OCO2),
154.2 (C, CCl3CH2OCO2), 164.0 (C, O2CPh), 169.6 [C, O2CCH3
(C-7 or C-9)], 169.9 [C, O2CCH3 (C-9 or C-7)]; FABMS
(thioglycerol) m/z 904 [MH]+, 787 [MH - PhCO2H]+, 767 [MH
- PhCO2H-H2O]+, 727 [MH - PhCO2H - AcOH]+.
(1H, br s), 5.50 (1H, br s), 6.25 (1H, d, J ) 10.7 Hz), 6.88 (1H,
d, J ) 10.7 Hz), 7.43 (2H, t, J ) 7.5 Hz, Hm-Ph), 7.58 (1H, t, J
) 7.5 Hz, Hp-Ph), 7.91 (2H, br d, J ) 7.5 Hz, Ho-Ph, in a 4:1
ratio with δ 8.03), 8.03 (2H, br d, J ) 7.5 Hz, Ho-Ph); 13C NMR
(CDCl3, 75 MHz) δ 8.8, 12.5, 14.0, 26.6 (4 CH3, C-16, C-17,
C-18, and C-19), 20.7, 21.1, 21.2 [3 CH3, O2CCH3 (C-5, C-7,
and C-9)], 27.5, 33.6 (2 CH2, C-2 + C-6), 39.0 (CH, C-3), 45.1
(C, C-8), 49.6 (CH2, C-14), 59.0 (C, C-1), 69.5, 70.1, 74.0, 77.2
(4 CH, C-5, C-7, C-9, and C-10), 75.2 (C, C-15), 114.3 (CH2,
C-20), 128.8, 129.5 (2 CH, C-2′ + C-3′), 129.4 (C, C-1′), 133.5
(CH, C-4′), 145.0, 147.0 (2 C, C-4 + C-12), 163.6 (C, O2CPh),
163.9 (C, C-11), 169.5, 169.8, 169.9 [3 C, O2CCH3 (C-5, C-7 +
C-9)], 207.3 [C, CdO (C-13)]; FABMS (NBA) m/z 597 [MH]+,
579 [MH - H2O]+, 537 [MH - AcOH]+, 475 [MH - PhCO2H]+,
457 [MH - PhCO2H - H2O]+, 415 [MH - PhCO2H - AcOH]+,
357 [MH - PhCO2H - 2 AcOH]+.
5,13-Bis(TES)br evifoliol (7). TESCl (80 µL, 0,48 mmol)
was added to a solution of 1 (106 mg, 0.19 mmol) and pyridine
(40 µL) in CH2Cl2 (1 mL). The reaction mixture was stirred
for 2 h, and TESCl (16 µL, 0.096 mmol) and pyridine (8 µL)
were added. After stirring 1.5 h, more TESCl (32 µL, 0.19
mmol) and pyridine (16 µL) were added, and the mixture was
stirred for 18 h. The reaction mixture was diluted with CH2Cl2
(2 mL), cooled to 5 °C for 22 h, and filtered through a pad of
Celite (0.5 cm). The solids were washed with EtOAc (2 mL),
and the combined filtrate was evaporated. The residue was
separated by radial chromatography (EtOAc-Hex, 1:4) to
afford 104 mg (69%) of 7 as a white powder: mp 121-123 °C;
(b) F r om NMO-TP AP Oxid a tion .20 Tetrapropylammo-
nium perruthenate (TPAP, 3 mg, 0.59 mmol) and N-methyl-
morpholine-N-oxide (NMO, 45 mg, 0.38 mmol, 2.3 equiv) were
added to a solution of 2 (96 mg, 0.16 mmol) in CH2Cl2 (2.5
mL) containing 4 Å-ms (500 mg). The reaction mixture was
stirred at room temperature for 2 h, and the disappearance of
the starting material, 2, was monitored by TLC analysis. TPAP
(1 mg, 0.20 mmol) was added, and the mixture was stirred for
2 h. One last addition of TPAP (1 mg, 0.20 mmol) was required,
and after 1.5 h of stirring, the reaction mixture was filtered
in a sintered glass funnel. The solids were washed with EtOAc
(2 mL), and the combined filtrate was concentrated and applied
on a pad of silica gel (1 cm, Pasteur pipet) and eluted with
EtOAc (10 mL). The eluent was removed under reduced
pressure, and the residue was purified by radial chromatog-
raphy (PE:Et2O, 1:3) to give 38.4 mg (40%) of enone 8. This
material has the same physical properties as that described
above.
[R]23 -10.2° (c 1.0, CH2Cl2); IR (KBr) νmax 3559, 2956, 1741,
D
1664, 1601, 1458, 1375, 1263, 1089, 1028, 1002, 907, 826, 742,
709, 605 cm-1; 1H NMR (CDCl3, 500 MHz) δ 0.59 [12H, q, J )
7.6 Hz, 2 Si(CH2CH3)3], 0.92 (3H, s, H-19), 0.95 [18H, t, J )
7.6 Hz, 2 Si(CH2CH3)3], 1.09 (3H, s, H-16), 1.36-1.43 (2H, m,
H-2R + H-14R), 1.37 (3H, s, H-17), 1.77 (3H, s, O2CCH3 (C-9
or C-7)], 1.65-1.79 (1H, m, H-6â), 1.82 (1H, m, H-6R), 1.98
(3H, s, H-18), 2.04 [3H, s, O2CCH3 (C-7 or C-9)], 2.21 (1H, dd,
J ) 13.2, 6.8 Hz, H-14â), 2.32 (1H, br t, J ) 13 Hz, H-2â),
2.70 [1H, br s, OH (C-15)], 3.01 (1H, d, J ) 9.1 Hz, H-3R),
4.25 (1H, br s, H-5â), 4.48 (1H, br t, J ) 6.8 Hz H-13â), 4.69
(1H, br s, H-20a), 5.00 (1H, s, H-20b), 5.70 (1H, dd J ) 10.7,
5.5 Hz, H-7R), 6.08 (1H, br d, J ) 10.4 Hz, H-9â), 6.63 (1H, br
d, J ) 10.4 Hz, H-10R), 7.43 (2H, t, J ) 7.5 Hz, Hm-Ph), 7.55
(1H, t, J ) 7.5 Hz, Hp-Ph), 7.89 (2H, br d, J ) 7.5 Hz, Ho-Ph);
13C NMR (CDCl3, 75 MHz) δ 4.65 (CH2, SiCH2), 4.75 (CH2,
SiCH2), 6.77 (CH3, SiCH2CH3) 6.86 (CH3, SiCH2CH3), 11.8
(CH3, C-18), 12.8 (CH3, C-19), 20.7 [CH3, O2CCH3 (C-9 or C-7)],
21.4 [CH3, O2CCH3 (C-7 or C-9)], 25.1 (CH3, C-17), 27.4 (CH3,
C-16), 29.7 (CH2, C-2), 37.0 (CH, C-3), 37.9 (CH2, C-6), 45.0
(C, C-8), 47.8 (CH2, C-14), 61.6 (C, C-1), 70.0 (CH, C-7), 70.7
(CH, C-10), 72.6 (CH, C-5), 76.0 (CH, C-13), 76.9 (CH, C-9),
77.2 (C, C-15), 109.3 (CH2, C-20), 128.6 (CH, C-3′), 129.4 (CH,
C-2′), 129.6 (C, C-1′), 132.7 (C, C-11), 133.0 (CH, C-4′), 151.1
(C, C-4), 151.8 (C, C-12), 164.1 (C, O2CPh), 169.6 [C, O2CCH3
(C-7 or C-9)], 169.9 [C, O2CCH3 (C-9 or C-7)]; FABMS
(thioglycerol) m/z 785 [MH]+, 725 [MH - AcOH]+, 663 [MH -
PhCO2H]+, 645 [MH - PhCO2H - H2O]+, 603 [MH - PhCO2H
- AcOH]+, 545 [MH - PhCO2H - 2 AcOH]+.
C-13, C-15 Oxygen Br id ge Com p ou n d 10. A solution of
1 (26 mg, 0.047 mmol) and p-toluenesulfonyl chloride (TsCl,
20 mg, 0.10 mmol) in pyridine (1 mL) containing 4 Å-ms (250
mg) was stirred at room temperature for 6 h. An additional
portion of TsCl (5 mg, 0.03 mmol) was added, and the mixture
was stirred for another 17 h. The reaction mixture was then
filtered through a sintered glass funnel, and the filtrate was
concentrated. The crude product was purified by radial chro-
matography (PE:CH2Cl2-EtOH, 15:4:1) to give 10.9 mg (44%)
of compound 10 as a white powder: mp 122-123 °C; [R]23
D
6.5° (c 0.49, CH2Cl2); IR (KBr) νmax 3447, 2957, 1734, 1653,
1601, 1457, 1368, 1267, 1245, 1092, 1067, 1026, 980, 910, 826,
803, 712 cm-1; 1H NMR (CDCl3, 500 MHz) δ 0.85 (3H, s, H-17),
1.22 (3H, s, H-19), 1.30 (3H, s, H-16), 1.75 (1H, ddd, J ) 13.5,
12.1, 2.8 Hz, H-6â), 1.80-2.30 [4H, m, H-2R, H-14R, H-14â +
OH (C-5)], 1.88 (3H, s, H-18), 1.99 [3H, s, O2CCH3 (C-7)], 2.04
[3H, s, O2CCH3 (C-9)], 2.08 (1H, ddd, J ) 13.5, 4.9, 2.8 Hz,
H-6R), 2.22 (1H, dd, J ) 14.4, 11.1 Hz, H-2â), 3.07 (1H, d, J )
11.0 Hz, H-3R), 4.40 (1H, distorted t, J ) 7.7 Hz, H-13R), 4.45
(1H, t, J ) 2.5 Hz, H-5â), 4.96 (1H, s, H-20a), 5.20 (1H, s,
H-20b), 5.22 (1H, d, J ) 6.0 Hz, H-9â), 5.55 (1H, dd, J ) 12.1,
4.9 Hz, H-7R), 6.25 (1H, d, J ) 6.0 Hz, H-10R), 7.47 (2H, t, J
) 7.5 Hz, Hm-Ph), 7.57 (1H, t, J ) 7.5 Hz, Hp-Ph), 8.0 (2H, d, J
) 7.5 Hz, Ho-Ph); 13C NMR (CDCl3, 75 MHz) δ 11.3 (CH3, C-19),
11.8 (CH3, C-18), 20.6 [CH3, O2CCH3 (C-9)], 21.0 [CH3, O2CCH3
(C-7)], 24.8 (CH2, C-2), 25.3 (CH3, C-17), 26.4 (CH3, C-16), 34.1
(CH2, C-6), 36.3 (CH, C-3), 46.1 (C, C-8), 51.4 (CH2, C-14), 61.6
(C, C-1), 67.3 (CH, C-10), 70.6 (CH, C-7), 73.1 (CH, C-9 or C-5),
73.2 (CH, C-5 or C-9), 79.4 (C, C-15), 82.9 (CH, C-13), 112.3
(CH2, C-20), 128.5 (CH, C-3′), 129.5 (CH, C-2′), 129.8 (C, C-1′),
133.0 (CH, C-4′), 137.3 (C, C-11), 146.8 (C, C-12), 150.8 (C,
C-4), 165.2 (C, O2CPh), 169.6 [C, O2CCH3 (C-9)], 170.5 [C,
O2CCH3 (C-7)]; FABMS (NBA) m/z 538 M+, 537 [M - H]+, 417
[MH - PhCO2H]+, 359 [MH - PhCO2H - AcOH]+, 298 [MH
- PhCO2H -2 AcOH]+; anal. C 68.98%, H 7.08%, calcd for
5-Acetyl-13-oxobr evifoliol (8). (a ) F r om P CC Oxid a -
tion . Pyridinium chlorochromate (PCC, 36 mg, 0.17 mmol) was
added to a solution of 2 (100 mg, 0.17 mmol) in CH2Cl2 (2 mL).
The reaction mixture was stirred for 16 h, and diethyl ether
(10 mL) was added. The solids were filtered through a pad of
Florisil (1.5 cm) and washed with ether (3 × 3 mL) and CH2Cl2
(5 mL), and the combined filtrate was concentrated. The
residue was purified by radial chromatography (2% MeOH-
CH2Cl2, EtOAc-Hex, 1:1) to give 78 mg (78%) of enone 8 as a
white powder: mp 215-219 °C, [R]23 -2.9° (c 1.0, CH2Cl2);
D
IR (KBr) νmax 3570, 2972, 1753, 1740, 1716, 1664, 1599, 1451,
1372, 1242, 1087, 1070, 1024, 959, 824, 807, 720, 668 cm-1
;
1H NMR (CDCl3, 500 MHz at 23 °C) δ 0.88 (3H, s), 0.98 (3H,
s), 1.21-1,28 (3H, m), 1.36 (3H, s), 1.64-1,70 (4H, br s), 1.7-
2.30 (8H, m), 2.35-2.60 (2H, s), 2.70 (2H, d, J ) 14 Hz), 2.79
[1H, br s, OH (C-15)], 4.94 (1H, br s), 5.30 (1H, s), 5.37 (1H,
br s), 5.49 (1H, br s), 6.24 (1H, br d), 6.79 (1H, br s), 7.43 (2H,
t, J ) 7.5 Hz, Hm-Ph), 7.58 (1H, t, J ) 7.5 Hz, Hp-Ph), 7.91 (2H,
br d, J ) 7.5 Hz, Ho-Ph); 1H NMR (CDCl3, 500 MHz at -10 °C)
δ 0.88 (3H, s), 0.94 (3H, s), 1.25 (3H, s), 1.37 (3H, s), 1.81 (3H,
s), 1.91 (3H, s), 2.10 (3H, s), 2.15 (3H, s), 2.42-2,66 (4H, m),
2.79 [1H, br s, OH (C-15)], 4.94 (1H, br s), 5.30 (1H, s), 5.37
C
31H38O8, C 69.13%, H 7.11%.
Ester ifica tion : Gen er a l P r oced u r e. To a solution con-
taining the alcohol (1 equiv), dipyridyl carbonate24 (2-DPC, 6
equiv), and dimethylamino pyridine (DMAP, 2 equiv) in dry
toluene at room temperature was added the appropriate
substituted acid (6 equiv), and the reaction mixture was stirred

Characterization of an abeo-Taxane
J ournal of Natural Products, 2004, Vol. 67, No. 5 843
overnight. The solvent from the reaction mixture was evapo-
rated under reduced pressure to dryness (without heating) to
give a crude mixture. Separation of this mixture with silica
gel (1 mm), using the specified eluents, gave the desired ester.
13r- a n d 5r-[(2′S)-3-P h en ylla cta te]br evifoliol (12 a n d
13). Following the general procedure, the (S)-(-)-acid, 11a (48
mg, 0.19 mmol), was coupled with 1 (18 mg, 0.032 mmol), and
the reaction mixture was stirred at rt for 24 h to give a mixture
of the corresponding C-13 (25% yield) and C-5 esters (35%
yield) as white solids, which after hydrolysis of the THP group
gave 12 and 13, both in 50% yield as white solids.
13r-[(2′S)-3-P h en ylla cta te]br evifoliol (12): IR (KBr) νmax
3550-3300, 2979, 1742, 1640, 1604, 1450, 1373, 1262, 1104,
1093, 1028, 713 cm-1; 1H NMR (CDCl3, 500 MHz) δ 0.92 (3H,
br s, H-19), 1.15 (3H, s, H-16), 1.19 (1H, dd, J ) 14, 7 Hz,
H-14R), 1.35 (3H, s, H-17), 1.45 (1H, d, J ) 14 Hz, H-2R), 1.62
[1H, br s, OH (C-5)], 1.75 (3H, br s, O2CCH3), 1.80 (1H, dd, J
) 14, 11 Hz, H-6â), 1.96 (3H, br s, H-18), 1.98 (1H, dd, J ) 14,
5 Hz, H-6R), 2.05 (3H, s, O2CCH3), 2.10 [1H, s, OH (C-2′)], 2.36
(1H, br dd, J ) 14, 8 Hz, H-2â), 2.55 (1H, dd, J ) 14, 7 Hz,
H-14â), 2.58-2.65 [1H, br s, OH (C-15)], 2.69 (1H, d, J ) 8
Hz, H-3R), 2.92 (1H, dd, J ) 14, 8 Hz, H-3′), 3.00 (1H, dd, J )
14, 4 Hz, H-3′), 4.02 (1H, dd, J ) 8, 4 Hz, H-2′), 4.46 (1H, br
s, H-5â), 4.86 (1H, s, H-20a), 5.25 (1H, s, H-20b), 5.45 (1H, br
t, J ) 7 Hz, H-13â), 5.56 (1H, dd, J ) 11, 5 Hz H-7R), 6.01-
6.12 (1H, br m, H-9â), 6.58-6.62 (1H, br d, J ) 10 Hz, H-10R),
7.12 (2H, d, J ) 7.5 Hz, Ho-Ph), 7.15-7.25 (3H, m, HAr) 7.40
(2H, t, J ) 7.5 Hz, HCOm-Ph), 7.54 (1H, t, J ) 7.5 Hz, HCOp-Ph),
7.84 (2H, d, J ) 7.5 Hz, HCOo-Ph); anal. C 68.08%, H 6.88%,
calcd for C40H48O11, C 68.16%, H 6.86%.
mmol) was coupled with compound 2 (30 mg, 0.050 mmol) in
boiling CH2Cl2 for 20 h. Workup and chromatography (CH2Cl2-
Et2O, 85:15) gave 16 (16 mg, 53% yield) as a white solid: mp
124-125 °C; IR (KBr) νmax 3581, 2981, 1742, 1718, 1639, 1451,
1373, 1313, 1238, 1093, 1027, 713 cm-1; 1H NMR (CDCl3, 400
MHz) δ 0.90 (3H, br s, H-19), 1.12 (3H, s, H-16), 1.31 (1H, dd,
J ) 14, 7 Hz, H-14R), 1.35 (3H, s, H-17), 1.46 (1H, d, J ) 14
Hz, H-2R), 1.73 (3H, br s, O2CCH3), 1.88 (1H, td, J ) 14, 4 Hz,
H-6â), 1.98 (1H, ddd, J ) 14, 5, 2 Hz, H-6R), 2.03 (3H, s,
O2CCH3), 2.05 (3H, s, O2CCH3), 2.08 (3H, s, H-18), 2.41 (1H,
br dd, J ) 14, 8 Hz, H-2â), 2.62 (1H, dd, J ) 14, 7.4 Hz, H-14â),
2.70 [1H, br s, OH (C-15)], 2.73 (1H, d, J ) 8 Hz, H-3R), 4.88
(1H, s, H-20a), 5.26 (1H, s, H-20b), 5.38 (1H, dd, J ) 4, 2 Hz,
H-5â), 5.57 (1H, br t, J ) 7.4 Hz, H-13â), 5.63 (1H, dd, J )
11.0, 5.0 Hz, H-7R), 6.09 (1H, br d, J ) 10.5 Hz, H-9â), 6.32
(1H, d, J ) 16 Hz, H-1′), 6.68 (1H, br d J ) 10.5 Hz, H-10R),
7.35-7.47 (7H, m, HAr), 7.54 (1H, t, J ) 7.5 Hz, HCOp-Ph), 7.65
(1H, d, J ) 16 Hz, H2′), 7.86 (2H, d, J ) 7.5 Hz, HCOo-Ph); anal.
C 69.37%, H 6.66%, calcd for C42H48O11, C 69.21%, H 6.64%.
5r-Acet yl-13r-[(2′S)-O-(t et r a h yd r op yr a n -2-yl)-3-p h e-
n ylla cta te]br evifoliol (17). Following the general procedure
described above, the (S)-(-)-acid, 11a (33 mg, 0.13 mmol), was
coupled with compound 2 (13 mg, 0.021 mmol). Workup and
chromatography (Hex-EtOAc, 7:3) gave 17 (10 mg, 55% yield)
as a white solid: 1H NMR (CDCl3, 400 MHz) δ 0.85 (3H, br s,
H-19), 1.08 (3H, s, H-16), 1.20-1.30 (1H, m, H-14R), 1.35 (3H,
s, H-17), 1.40-1.60 (7H, br m, H-2R + (CH2)3], 1.73 (3H, br s,
O2CCH3), 1.75-1.95 (2H, m, H-6R, H-6â), 1.97 (3H, br s, H-18),
2.03 (3H, s, O2CCH3), 2.05 (3H, s, O2CCH3), 2.35 (1H, br dd, J
) 13.9, 9.1 Hz, H-2â), 2.51 (1H, dd, J ) 13.9, 7.4 Hz, H-14â),
2.64 [1H, br s, OH (C-15)], 2.68 (1H, d, J ) 9.1 Hz, H-3R),
2.92 (1H, dd, J ) 14, 6 Hz, H-3′), 3.00 (1H, dd, J ) 14, 7.5 Hz,
H-3′), 3.32-3.41 (1H, m, OCH2), 3.75-3.85 (1H, m, OCH2), 4.25
(1H, dd, J ) 7.5, 6 Hz, H-2′), 4.40 (1H, t, J ) 3 Hz, R-OCHO-
R), 4.88 (1H, s, H-20a), 5.28 (1H, s, H-20b), 5.35-5.40 (1H, br
s, H-5â), 5.45 (1H, t, J ) 7.4 Hz, H-13â), 5.56 (1H, dd, J )
11.0, 5.0 Hz, H-7R), 6.06 (1H, br d, J ) 10 Hz, H-9â), 6.65
(1H, d, J ) 10.4 Hz, H-10R), 7.10-7.25 (5H, m, HAr), 7.45 (2H,
t, J ) 7.5 Hz, HCOm-Ph), 7.54 (1H, t, J ) 7.5 Hz, HCOp-Ph), 7.87
(2H, d, J ) 7.5 Hz, HCOo-Ph); anal. C 67.72%, H 6.99%, calcd
for C47H58O13, C 67.92%, H 7.04%.
5r-Acet yl-13r-[(2′S)-3-p h en ylla ct a t e]b r evifoliol (18).
Hydrolysis of compound 17 (10 mg) was carried out in EtOH
(1 mL) in the presence of p-toluenesulfonic acid. The reaction
mixture was stirred at room temperature for 16 h, after which
time the solvent was removed under reduced pressure, leaving
a crude residue. Separation of this mixture with silica gel
(CH2Cl2-Et2O, 85:15) gave compound 18 (5 mg) in 56% yield
as a white solid: mp 87-88 °C; IR (KBr) νmax 3560-3300, 2980,
1742, 1452, 1373, 1236, 1093, 1028, 713 cm-1; 1H NMR (CDCl3,
400 MHz) δ 0.90 (3H, br s, H-19), 1.10 (3H, s, H-16), 1,19 (1H,
dd, J ) 14, 7 Hz, H-14R), 1.24 [1H, s, OH (C-2′)], 1.35 (3H, s,
H-17), 1.45 (1H, d, J ) 14 Hz, H-2R), 1.73 (3H, br s, O2CCH3),
1.78-1.92 (2H, m, H-6R, H-6â), 1.96 (3H, br s, H-18), 2.02 (3H,
s, O2CCH3), 2.05 (3H, s, O2CCH3), 2.38 (1H, br dd, J ) 14, 8
Hz, H-2â), 2.56 (1H, dd, J ) 14, 7.4 Hz, H-14â), 2.53-2.66
[1H, br s, OH (C-15)], 2.64 (1H, d, J ) 8 Hz, H-3R), 2.95 (1H,
dd, J ) 14, 8 Hz, H-3′), 3.08 (1H, dd, J ) 14, 4 Hz, H-3′), 4.29
(1H, dd, J ) 8.0, 4 Hz, H-2′), 4.88 (1H, s, H-20a), 5.27 (1H, s,
H-20b), 5.35-5.40 (1H, br s, H-5â), 5.43-5.48 (1H, br t, J )
7.4 Hz, H-13â), 5.58 (1H, dd, J ) 11.0, 5.0 Hz, H-7R), 6.01-
6.12 (1H, br m, H-9â), 6.58-6.65 (1H, br d, J ) 10 Hz, H-10R),
7.14-7.25 (5H, m, HAr), 7.42 (2H, t, J ) 7.5 Hz, HCOm-Ph), 7.54
(1H, t, J ) 7.5 Hz, HCOp-Ph), 7.86 (2H, d, J ) 7.5 Hz, HCOo-Ph);
FABMS m/z 746 (M+ - PhCO, -CH3), 626, 540, 401, 358, 341,
221, 239, 220, 185, 184, 148, 105, 91; anal. C 67.45%, H 6.68%,
calcd for C42H50O12, C 67.54%, H 6.75%.
5r-[(2′S)-3-P h en ylla cta te]br evifoliol (13): IR (KBr) νmax
3565, 2970, 1741, 1715, 1663, 1601, 1445, 1380, 1305, 1250,
1
1134, 1088, 1070, 963, 805, 759, 716 cm-1; H NMR (CDCl3,
400 MHz) δ 0.90 (3H, br s, H-19), 1.03 (3H, s, H-16), 1.05-
1.16 (1H, m, H-14R), 1.34 (3H, s, H-17), 1.35-1.55 [3H, m,
H-2R, OH (C-2′) + OH (C-13)], 1.75 (3H, br s, O2CCH3), 1.86-
1.98 (1H, m, H-6R), 2.04 (3H, s, O2CCH3), 2.09 (3H, br s, H-18),
2.15 (1H, br d, J ) 14 Hz, H-6â), 2.42 (1H, br dd, J ) 14, 9
Hz, H-2â), 2.52 (1H, dd, J ) 14, 7 Hz, H-14â), 2.76 (1H, d, J
) 8 Hz, H-3R), 2.83 [1H, br s, OH (C-15)], 2.94 (1H, dd, J )
14, 8 Hz, H-3′), 3.12 (1H, dd, J ) 14, 6 Hz, H-3′), 4.22 (1H, dd,
J ) 8, 6 Hz, H-2′), 4.42 (1H, br t, J ) 7 Hz H-13â), 4.94 (1H,
s, H-20a), 5.31 (1H, br s, H-5â), 5.35 (1H, s, H-20b), 5.59 (1H,
dd, J ) 11, 5 Hz H-7R), 5.97-6.07 (1H, br d, J ) 10 Hz, H-9â),
6.62 (1H, d, J ) 10 Hz, H-10R), 7.14 (2H, d, J ) 7.5 Hz, Ho-Ph),
7.17-7.28 (3H, m, HAr) 7.42 (2H, t, J ) 7.5 Hz, HCOm-Ph), 7.54
(1H, t, J ) 7.5 Hz, HCOp-Ph), 7.86 (2H, d, J ) 7.5 Hz, HCOo-Ph);
anal. C 67.94%, H 6.83%, calcd for C40H48O11, C 68.16%, H
6.86%.
13r-P h en ylisoser in a tebr evifoliol (15). Following the
general procedure, (2R,3S)-(-)-2-(tetrahydropyran-2-yloxy)-3-
phenylmethanamido)propanoic acid, 1425 (34 mg, 0.092 mmol),
was coupled with compound 1 (10 mg, 0.018 mmol) to give the
corresponding C-13 ester (13.7 mg, 86% yield). Hydrolysis of
the THP group (13.7 mg, 0.016 mmol) with the p-toluene-
sulfonic acid in EtOH gave the alcohol derivative 15 (6.8 mg,
51% yield): mp 150-152 °C; IR (KBr) νmax 3499, 3435, 3017,
2933, 1731, 1660, 1651, 1450, 1370, 1120, 1080, 969, 805, 735
cm-1; 1H NMR (CDCl3, 400 MHz) δ 0.87 (3H, br s, H-19), 1.04
(3H, s, H-16), 1,14 (1H, dd, J ) 14, 8 Hz, H-14R), 1.23 (3H, s,
H-17), 1.27 [1H, d, J ) 4,0 Hz, OH (C-5)] 1.73 (3H, s, O2CCH3),
1.78 (1H, d, J ) 14 Hz, H-2R), 1.92-2.00 (2H, m, H-6R, H-6â),
2.05 (3H, s, O2CCH3), 2.09 (3H, s, H-18), 2.28 (1H, dd, J ) 14,
9 Hz, H-2â), 2.44 (1H, dd, J ) 14, 7 Hz, H-14â), 2.64 [1H, br
s, OH (C-15)], 2.98 (1H, d, J ) 9 Hz, H-3R), 3.34 [1H, d, J )
3,0 Hz, OH (C-2′)] 4.37 (1H, br s, H-5â), 4.72 (1H, t, J ) 3 Hz,
H-2′), 5.10 (1H, s, H-20a), 5.33 (1H, s, H-20b), 5.48 (1H, br t,
J ) 7 Hz H-13â), 5.64-5.72 (2H, m, H-7R + H-3′), 5.97 (1H,
br d, J ) 10 Hz, H-9â), 6.53 (1H, d, J ) 10 Hz, H-10R), 7.11
(1H, d, J ) 9.4 Hz, N-H), 7.30-7.61 (11H, m, HAr), 7.72 (2H,
d, J ) 7.5 Hz, HAr), 7.85 (2H, d, J ) 8.0 Hz, HAr); anal. C
68.28%, H 6.50%, N 1.70%, calcd for C47H53NO12, C 68.50%, H
6.48%, N 1.69%.
5r-Acetyl-13r-[(2′R)-3-p h en ylla cta te]br evifoliol (19).
Following the general procedure, the coupling of the (2R)-(+)-
acid, 11b (62.5 mg, 6 equiv), with compound 2 (24.8 mg, 1
equiv) and subsequent hydrolysis of the THP ether (12.5 mg,
36% yield) gave the corresponding free alcohol 19 (9.2 mg,
86.7% yield), as a white solid: mp 91-92 °C; IR (KBr) νmax
3575-3400, 3000-2900, 1742, 1453, 1372, 1236, 1094, 1027,
5r-Acetyl-13r-cin n a m oylbr evifoliol (16). Following the
general procedure described above, cinnamic acid (30 mg, 0.20
1
915, 755 cm-1; H NMR (CDCl3, 400 MHz) δ 0.93 (3H, br s,

844 J ournal of Natural Products, 2004, Vol. 67, No. 5
Tremblay et al.
2947, 1731, 1370, 1220, 1162, 1065, 845 cm-1 1H NMR
H-19), 1.11 (3H, s, H-16), 1,23-1.339 (1H, m, H-14R), 1.35 (3H,
s, H-17), 1.48 (1H, br d, J ) 14 Hz, H-2R), 1.73 (3H, br s, O2-
CCH3), 1.78-2.07 (2H, m, H-6R, H-6â), 1.92 (3H, br s, H-18),
2.02 (3H, s, O2CCH3), 2.05 (3H, s, O2CCH3), 236-2.44 [2H, br
dd, J ) 14, 8 Hz, H-2â + OH (C-2′)], 2.54-2.64 (2H, br dd, J
) 14, 7 Hz, H14â + OH (C-15)], 2.67 (1H, d, J ) 8 Hz, H-3R),
2.92 (1H, dd, J ) 14, 8 Hz, H-3′), 3.06 (1H, dd, J ) 14, 6 Hz,
H-3′), 4.38 (1H, dd, J ) 8, 6 Hz, H-2′), 4.94 (1H, s, H-20a),
5.30 (1H, s, H-20b), 5.36-5.44 (1H, br s, H-5â), 5.53-5.67 (2H,
m, H-7R and H-13â), 6.05-6.16 (1H, br m, H-9â), 6.60-6.66
(1H, br d, J ) 10 Hz, H-10R), 7.15 (2H, d, J ) 7.5 Hz, Ho-Ph),
7.18-7.20 (3H, m, HAr), 7.42 (2H, t, J ) 7.5 Hz, HCOm-Ph), 7.55
(1H, t, J ) 7.5 Hz, HCOp-Ph), 7.86 (2H, d, J ) 7.5 Hz, HCOo-Ph);
FABMS m/z 746 (M+ - PhCO, -CH3), 626, 540, 401, 358, 341,
238, 221, 220, 185, 184, 148, 105, 91; anal. C 67.68%, H 6.72%,
calcd for C42H50O12, C 67.54%, H 6.75%.
;
(CD2Cl2, 400 MHz) δ 0.09 (3H, s, SiCH3), 0.12 (3H, s, SiCH3),
0.90 (3H, s, H-19), 0.92 (9H, s, Si(CH3)3), 1.07 (3H, s, H-16),
1,00-1.10 (1H, m, H-14R), 1.25 (1H, d, J ) 14 Hz, H-2R), 1.28
(3H, s, H-17), 1.60-1.75 (3H, m, H-6â, H-6R + OH), 1.89 (3H,
br s, O2CCH3), 1.96-2.03 (6H, br s, 2 × O2CCH3), 2.06 (3H, s,
H-18), 2.22 (1H, m, H-2â), 2.33 (1H, d, J ) 8 Hz, H-3R), 2.62
(1H, dd, J ) 14, 7.4 Hz, H-14â), 2.85 [1H, br s, OH (C-15)],
3.43-3.50 (1H, br s, OH), 3.55, 3.66 (each 1H, br d, J ) 10
Hz, H-20), 3.8 (1H, br s, H-5â), 5.47-5.55 (2H, m, H-13â +
H-9â), 5.57 (1H, dd, J ) 14, 5.0 Hz, H-7R), 6.36-6.47 (1H, br
s, H-10R), 7.42 (2H, t, J ) 7.5 Hz, HCOm-Ph), 7.54 (1H, t, J )
7.5 Hz, HCOp-Ph), 7.90 (2H, br d, J ) 7.5 Hz, HCOo-Ph).
13r-Acet yl-20-ter t-b u t yld im et h ylsilyloxy-5-m et h a n e-
su lfon yl-4r-h yd r oxybr evifoliol (23). The above alcohol
precursor (13 mg, 0.0174 mmol) was treated with mesyl
chloride (6.75 mL, 0.087 mmol, 5 equiv) in pyridine (3 mL)
and 3 Å molecular sieves (50 mg). The reaction mixture was
stirred at room temperature for 24 h, then filtered through
Celite and rinsed with CH2Cl2. Evaporation of the solvents
under reduced pressure followed by separation of the crude
material with silica gel (CH2Cl2-EtOAc, 8:2) gave the mesy-
lated product 23 (31.1 mg, 73% yield): mp 109-110 °C; IR
(KBr) νmax 3505, 2933, 1741, 1452, 1372, 1245, 1179, 1086,
5r-Acetyl-13r-p h en ylisoser in a tebr evifoliol (20). The
acid 1425 (37 mg, 0.1 mmol) was coupled with compound 2 (10
mg, 0.0167 mmol) as above to give the corresponding C-13
ester (15.6 mg, 45% yield). Hydrolysis of the THP group (4.7
mg, 6.8 × 10-2 mmol) with the p-toluenesulfonic acid in EtOH
gave the alcohol derivative 20 (1.5 mg, 35% yield): IR (KBr)
νmax 3437, 2983, 1739, 1713, 1601, 1445, 1320, 1240, 1145,
1
1070, 955, 809, 729 cm-1; H NMR (CDCl3, 400 MHz) δ 0.92
(3H, br s, H-19), 1.10 (3H, s, H-16), 1.20-1.32 (1H, m, H-14R),
1.35 (3H, s, H-17), 1.51 (1H, d, J ) 14 Hz, H-2R), 1.68-1.78
(3H, br s, O2CCH3), 1.82-2.00 (2H, m, H-6R, H-6â), 1.90 (6H,
s, 2 × O2CCH3), 2.05 (3H, s, H-18), 2.30-2.45 (2H, m, H-2â +
H-14â), 2.55-2.66 [1H, br s, OH (C-15)], 2.70 (1H, d, J ) 9
Hz, H-3R), 3.24 [1H, d, J ) 6.0 Hz, OH (C-2′)], 4.63 (1H, dd, J
) 6.0, 2.7 Hz, H-2′), 4.94 (1H, s, H-20a), 5.30 (1H, s, H-20b),
5.39-5.42 (1H, br s, H-5â), 5.56 (1H, dd, J ) 11.0, 5.0 Hz,
H-7R), 5.62 (1H, dd, J ) 9.4, 2.7 Hz, H-3′), 5.68-5.75 (1H, br
t, J ) 7.4 Hz, H-13â), 6.05-6.12 (1H, br d, J ) 10 Hz, H-9â),
6.58-6.64 (1H, br d, J ) 10 Hz, H-10R), 6.95 (1H, d, J ) 9.4
Hz, N-H), 7.30-7.60 (11H, m, HAr), 7.72 (2H, d, J ) 7.5 Hz,
1034, 841 cm-1 1H NMR (CD2Cl2, 400 MHz) δ 0.08 (3H, s,
;
SiCH3), 0.09 (3H, s, SiCH3), 0.88 (3H, s, H-19), 0.90 (9H, s,
Si(CH3)3), 1.07 (3H, s, H-16), 1,04-1.13 (1H, m, H-14R), 1.25-
1.30 (1H, d, J ) 14 Hz, H-2R), 1.30 (3H, s, H-17), 1.70-2.05
(3H, br m, H-6â, H-2â + OH), 1.80 (3H, br s, O2CCH3), 1.85
(3H, s, O2CCH3), 2.00 (3H, br s, O2CCH3), 2.02 (3H, s, H-18),
1.88 (1H, dt, J ) 14, 4 Hz, H-6R), 2.23 [1H, s, OH (C-15)], 2.25
(1H, d, J ) 8 Hz, H-3R), 2.37 (dd, J ) 14, 7.4 Hz, 1H, H-14â),
3.15 (3H, s, O2SCH3), 3.52-3.62 (1H, br s, H-20), 3.73 (1H, d,
J ) 10 Hz, H-20), 5.00 (1H, br s, H-5â), 5.40-5.50 (1H, br m,
H-9â), 5.48 (1H, br d, J ) 14 Hz, H-7R), 5.56 (1H, br s, H-13â),
6.30-6.43 (1H, br s, H-10R), 7.42 (2H, t, J ) 7.5 Hz, HCOm-Ph),
7.54 (1H, t, J ) 7.5 Hz, HCOp-Ph), 7.89 (2H, br s, HCOo-Ph); anal.
C 58.35%, H 7.37%, calcd for C40H60O14SSi, C 58.23%, H 7.33%.
13r-Acet yl-4r,20-d ih yd r oxy-5-m et h a n esu lfon ylb r evi-
foliol (24). Deprotection of the primary alcohol group of 23 (8
mg, 0.01 mmol) with TBAF (dry, 1.0 M solution in THF, 14.5
µL) in THF (1.0 mL) gave derivative 24 (3 mg, 66% yield, based
on recovered starting material): IR (KBr) νmax 3455, 2928,
1734, 1446, 1375, 1340, 1220, 1170, 1056, 1048, 843 cm-1; 1H
NMR (CD2Cl2, 400 MHz) δ 1.09 (3H, s, H-19), 1.18 (3H, s,
H-16), 1.16-1.26 (1H, m, H-14R), 1.30 (3H, s, H-17), 1.53 (1H,
d, J ) 14 Hz, H-2R), 1.70-1.95 (3H, br m, H-6â, H-2â + OH),
1.77 (3H, br s, O2CCH3), 1.89 (3H, s, O2CCH3), 1.92 (3H, br s,
O2CCH3), 1.99 (3H, s, H-18), 2.05 [1H, s, OH (C-15)], 2.15 (1H,
dt, J ) 14, 4 Hz, H-6R), 2.20 (1H, br d, J ) 8 Hz, H-3R), 2.33
(1H, dd, J ) 14, 7.4 Hz, H-14â), 3.11 (3H, s, O2SCH3), 3.57,
3.66 (each 1H, d, J ) 11 Hz, H-20), 4.51 (1H, s, OH), 5.07 (1H,
br s, H-5â), 5.24 (1H, dd, J ) 14, 5.0 Hz, H-7R), 5.34-5.41
(1H, m, H-9â), 5.51 (1H, br t, J ) 7.4 Hz, H-13â), 6.19-6.34
(1H, br s, H-10R), 7.37 (2H, t, J ) 7.5 Hz, HCOm-Ph), 7.52 (1H,
t, J ) 7.5 Hz, HCOp-Ph), 7.76-7.86 (2H, br s, HCOo-Ph).
H
Ar), 7.84 (2H, d, J ) 8.0 Hz, HAr); anal. C 68.04%, H 6.47%,
N 1.59%, calcd for C49H55NO13, C 67.96%, H 6.40%, N 1.62%.
13r-Acetyl-4r,20-d ih yd r oxybr evifoliol (21). Compound
3 (87 mg, 0.15 mmol) was dihydroxylated with OsO4 (1.8 mg,
0.0071 mmol, 0.05 equiv) and N-methylmorpholine-N-oxide
(18.7 mg, 1.1 equiv) in acetone (1.5 mL) and water-t-BuOH
(6:1). The reaction mixture was stirred at room temperature
overnight. Once the reaction was complete, Fluorisil (40 mg),
sodium hydrosulfite (25 mg), and water (2 mL) were added.
Extraction was carried out in ethyl acetate (6 × 15 mL) and
diethyl ether (7 × 5 mL). The combined extracts were dried
over MgSO4 and filtered, and then the solvent was removed
under reduced pressure to leave a crude material (85 mg).
Separation of this material with silica gel (CH2Cl2-MeOH, 95:
5; 9:1) gave 65.7 mg (72%) of pure triol 21, which crystallized
upon drying under vacuum: mp 134-135 °C; IR (KBr) νmax
3575-3331, 2980, 1733, 1375, 1251, 1031, 714 cm-1; 1H NMR
(CDCl3, 400 MHz) δ 1.05 (3H, br s, H-19), 1.23-1.26 (1H, m,
H-14R), 1.28 (3H, s, H-16), 1.75-1.90 (10H, br s, H-17, H-2R,
+ 2 × O2CCH3), 2.00 (3H, s, O2CCH3), 1.95-2.10 (2H, m, H-6â
+ H-6R), 2.05 (3H, s, H-18), 2.15-2.23 (1H, br s, OH), 2.23-
2.34 (2H, m, H-2â + H-3R), 2.38 (1H, dd, J ) 14, 7.4 Hz,
H-14â), 2.50-2.55 (1H, br s, OH), 3.25-3.35 (1H, m, OH),
3.62-3.75 (3H, br m, H-20 + OH), 4.40 (1H, br s, H-5â), 5.43-
5.51 (1H, m, H-9â), 5.51-5.60 (2H, m, H-7R + H-13â), 6.32-
6.44 (1H, br s, H-10R), 7.44 (2H, t, J ) 7.5 Hz, HCOm-Ph), 7.54
(1H, t, J ) 7.5 Hz, HCOp-Ph), 7.90 (2H, br d, J ) 7.5 Hz,
Com p ou n d 25. Compound 24 (3.0 mg, 0.0044 mmol) was
treated with tetrabutylammonium acetate (12 mg, 9 equiv) in
butanone (1.0 mL). The reaction mixture was stirred under
reflux for 19 h. Separation of this crude mixture with silica
gel (CH2Cl2-Et2O, 4:1) gave the hydroxyoxetane derivative 25
(1.2 mg, 44% yield): IR (KBr) νmax 3550, 2958, 1728, 1708,
1445, 1385, 1226, 1171, 1046, 863 cm-1; 1H NMR (CD2Cl2, 400
MHz) δ 1.09 (3H, s, H-19), 1.20 (3H, s, H-16), 1.28 (3H, s,
H-17), 1.30 (1H, dd, J ) 14, 7 Hz, H-14R), 1.39 (1H, d, J ) 14
Hz, H-2R), 1.65 (3H, br s, O2CCH3), 1.67-1.84 (2H, br m, H-6â,
+ OH), 2.01 (3H, s, O2CCH3), 2.03 (3H, s, O2CCH3), 2.04 (3H,
s, H-18), 2.05-2.10 (1H, m, H-6R), 2.30 (1H, br dd, J ) 14, 8
Hz, H-2â), 2.58 (1H, dd, J ) 14, 7 Hz, H-14â), 2.77 (1H, br d,
J ) 8 Hz, H-3R), 2.92 [1H, s, OH (C-15)], 4.36 (1H, d, J ) 8.1
Hz, H-20a), 4.52 (1H, d, J ) 8.1 Hz, H-20b), 5.15 (1H, br s,
H-5R), 5.37 (1H, dd, J ) 14, 5.0 Hz, H-7R), 5.60 (1H, br t, J )
7 Hz, H-13â), 6.98 (1H, br d, J ) 10.5 Hz, H-9â), 7.15 (1H, br
d, J ) 10.5 Hz, H-10R), 7.46 (2H, t, J ) 7.5 Hz, HCOm-Ph), 7.62
(1H, t, J ) 7.5 Hz, HCOp-Ph), 8.04 (2H, d, J ) 7.5 Hz, HCOo-Ph);
H
COo-Ph); anal. C 62.78%, H 6.99%, calcd for C33H44O12, C
62.64%, H 7.01%.
13r-Acetyl-20-(tbu tyld im eth ylsilyloxy)-4r-h yd r oxybr e-
vifoliol (21a ). The primary alcohol of triol 21 (17 mg, 0.027
mmol) was treated with tert-butyldimethylsilyl chloride (22.2
mg, 0.147 mmol, 5.5 equiv) and imidazole (24.5 mg, 0.36 mmol,
13.5 equiv) in CH2Cl2 (2 mL) containing 4 Å-ms (100 mg). The
reaction mixture was stirred at rt for 18 h (TLC analysis) and
filtered through Celite and then the solvent was removed
under reduced pressure. Separation of the crude material with
silica gel (Hex-EtOAc, 1:1) gave 17.8 mg (88% yield) of the
silyl ether derivative 21a : mp 111-112 °C; IR (KBr) νmax 3450,

Characterization of an abeo-Taxane
J ournal of Natural Products, 2004, Vol. 67, No. 5 845
FABMS (NBA) m/z 555 (M+ - CH3CO2), 531, 515, 484; anal.
C 64.39%, H 6.90%, calcd for C33H42O11, C 64.48%, H 6.89%.
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Ack n ow led gm en t. We express our gratitude to UQAM
Foundation and the Department of Chemistry, UQAM, for
their financial support. Financial support from the Natural
Sciences and Engineering Research Council of Canada (NSERC)
and F.C.A.R. Funds (Quebec) are also acknowledged. The
authors also wish to acknowledge Prof. E. Piers for supervising
part of this work and the Department of Chemistry, University
of British Columbia, for the use of laboratory facilities. Special
thanks to Dr. H. L. Thanh for recording of the 2D 500 MHz
NMR spectra, R. M. Dubois for providing assistance with the
editing of data tables, and K. Walsh for providing assistance
with the preparation of the manuscript.
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Su p p or tin g In for m a tion Ava ila ble: Procedures for isolation of
1 and for the preparation of compounds 2-4; Tables S1 of 1H and S2
of 13C NMR spectral data for compounds 1-7 and 10, copies of IR
spectra for compounds 1-4, 8, and 10, and 300 or 500 MHz 1H and
13C NMR spectra for compounds 1, 8, and 10 and 2D NMR spectra for
10. This material is available free of charge via the Internet at http://
pubs.acs.org.
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