Concise synthesis of PM-94128 and Y-05460M-A

Article abstract of DOI:10.1021/jo9014968

(Chemical Equation Presented) The enantioselective total synthesis of PM-94128, a potent cytotoxin of microbial origin, was accomplished by a concise nine-step sequence of reactions in 14% overall yield from N-Boc-L-leucine. The synthesis of Y-05460M-A, a

Full text of DOI:10.1021/jo9014968

pubs.acs.org/joc
Concise Synthesis of PM-94128 and Y-05460M-A
Masaru Enomoto and Shigefumi Kuwahara*
Laboratory of Applied Bioorganic Chemistry, Graduate
School of Agricultural Science, Tohoku University,
Tsutsumidori-Amamiyamachi, Aoba-ku, Sendai 981-8555,
Japan
skuwahar@biochem.tohoku.ac.jp
Received July 13, 2009
FIGURE 1. Structures of PM-94128, Y-05460M-A, and related
natural products.
the culture broths of Bacillus sp. PhM-PHD-090 and Bacillus
sp. Y-05460M, respectively, are also among this type of
natural products. PM-94128 (1) was shown to exhibit potent
cytotoxicity against several tumor cell lines (P-388, A-549,
HT-29, MEL-28) with an IC50 value of 50 nM,8 while
Y-05460-A (2) was found to be highly toxic to L1210 and
P388 cancer cell lines with IC50 values of 130 and 45 nM,
respectively.9 The structure of 1 was originally proposed as
its planar structure on the basis of spectroscopic analyses,
and its absolute configuration was unambiguously deter-
mined by Py and co-workers through their synthetic study,10
in which they assumed that the stereochemistry of 1 would
probably be the same as that of AI-77-B from biogenetic
considerations. As part of our continuing efforts for the
synthesis of isocoumarin-unusual amino acid conjugate-
type natural products,11 we planned to assign the unknown
stereochemistry of the analogous compound 2 by synthetic
means as well as to develop a concise general approach to this
type of compounds. We describe herein the expeditious
enantioselective total synthesis of 1 and a stereoisomer of
2, which led to the determination of the absolute configura-
tion of Y-05460M-A (2).
The enantioselective total synthesis of PM-94128, a po-
tent cytotoxin of microbial origin, was accomplished by a
concise nine-step sequence of reactions in 14% overall
yield from N-Boc-L-leucine. The synthesis of Y-05460M-A,
a one-carbon lower homologue of PM-94128, was also
achievedfromN-Boc-L-valine by the same approach, which
enabled its stereochemical determination.
A small family of natural products characterized by a
dihydroisocoumarin ring system linked to an unusual dihy-
droxyamino acid through an amide bond, as exemplified by
amicoumacin A and AI-77-B (Figure 1),1 have been reported
to possess various intriguing biological properties such as
antibacterial,1-5 anti-inflammatory,1,3,4 antiulcer,1,3,4 herbi-
cidal,6 and cytotoxic activities.2,7 PM-94128 (1) and its
one-carbon lower homologue Y-05460M-A (2) isolated from
Our retrosynthetic analysis of 1 is shown in Scheme 1.
Compound 1 should be obtainable via condensation of amine
segment 3 and acid segment 4, the latter of which would be
derived from hydrolysis of N-protected lactam 5. The dihy-
droxy lactam 5 was considered to be readily accessible by
stereoselective dihydroxylation of unsaturated lactam 6,
which would be traced back to N-Boc-protected L-leucine 7.
Based on the synthetic plan described above, our synthesis
of PM-94128 (1) began with the conversion of 7 into known
(1) (a) Itoh, J.; Omoto, S.; Shomura, T.; Nishizawa, N.; Miyado, S.;
Yuda, Y.; Shibata, U.; Inouye, S. J. Antibiot. 1981, 34, 611–613. (b) Itoh, J.;
Shomura, T.; Omoto, S.; Miyado, S.; Yuda, Y.; Shibata, U.; Inouye, S. Agric.
Biol. Chem. 1982, 46, 1255–1259. (c) Shimojima, Y.; Hayashi, H.; Ooka, T.;
Shibukawa, M. Agric. Biol. Chem. 1982, 46, 1823–1829. (d) Shimojima, Y.;
Shirai, T.; Baba, T.; Hayashi, H. J. Med. Chem. 1985, 28, 3–9.
(2) Okazaki, H.; Kishi, T.; Beppu, T.; Arima, K. J. Antibiot. 1975, 28,
717–719.
(3) McInerney, B. V.; Taylor, W. C.; Lacey, M. J.; Akhurst, R. J.;
Gregson, R. P. J. Nat. Prod. 1991, 54, 785–795.
(4) Pinchuk, I. V.; Bressollier, P.; Sorokulova, I. B.; Verneuil, B.; Urdaci,
M. C. Res. Microbiol. 2002, 153, 269–276.
(5) Pinchuk, I. V.; Bressollier, P.; Verneuil, B.; Fenet, B.; Sorokulova,
ꢀ
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3156–3161.
~
ꢀ
(8) Canedo, L. M.; Fernandez Puentes, J. L.; Baz, J. P. J. Antibiot. 1997,
50, 175–176.
(9) Sato, T.; Nagai, K.; Suzuki, K.; Morioka, M.; Saito, T.; Nohara, C.;
Susaki, K.; Takebayashi, Y. J. Antibiot. 1992, 45, 1949–1952.
(10) Patel, S. K.; Murat, K.; Py, S.; Vallee, Y. Org. Lett. 2003, 5, 4081–
4084.
(11) For syntheses of AI-77-B and related natural products, see: Enomoto,
M.; Kuwahara, S. Angew. Chem., Int. Ed. 2009, 48, 1144–1148. and references
cited therein.
€
(6) (a) Gebhardt, K.; Schimana, J.; Muller, J.; Fiedler, H.-P.; Kallenborn,
€
€
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Schmid, D. G.; Rheinheimer, J; Dettner, K. FEMS Microbiol. Lett. 2002,
217, 199–205. (b) Azumi, M.; Ogawa, K.; Fujita, T.; Takeshita, M.; Yoshida,
R.; Furumai, T.; Igarashi, Y. Tetrahedron 2008, 64, 6420–6425.
(7) Huang, Y.-F.; Li, L.-H.; Tian, L.; Qiao, L.; Hua, H.-M.; Pei, Y.-H.
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ꢀ
7566 J. Org. Chem. 2009, 74, 7566–7569
Published on Web 09/01/2009
DOI: 10.1021/jo9014968
r
2009 American Chemical Society

Enomoto and Kuwahara
JOCNote
SCHEME 1. Retrosynthetic Analysis of 1
SCHEME 2
β-hydroxy lactam 8 in ca. 70% yield by a convenient three-
step sequence involving the acylation of Meldrum’s acid with
7, which was originally developed by Jouin and Castro and
later modified by Ma and co-workers.12,13 Subjection of 8 to
a one-pot mesylation/elimination protocol quantitatively
provided dehydration product 6, which was then exposed
to dihydroxylation conditions to give 9 as a single diaster-
eomer, albeit in a moderate isolated yield of 58%.14,15 After
protection of the diol 9 as its acetonide 10, the product was
hydrolyzed with aq LiOH in the presence of a catalytic
amount of H2O2 to furnish the acid segment 11 (Scheme 2).
With the acid segment 11 in hand, we proceeded to the
final stage of the synthesis of PM-94128 (1). The carboxylic
acid 11 was condensed with the known amine segment 3,
prepared by our epoxide ring-opening approach,11 to give
amide 12. Exposure of 12 to BBr3 in CH2Cl2 brought about
deprotection of all of its three protecting groups to afford 1 in
an acceptable yield of 67%. The 1H and 13C NMR spectra of
1 were identical with those reported previously,8,10 and the
specific rotation of 1 ([R]22D -94.1 (c 0.195, CHCl3)) showed
SCHEME 3
good agreement with literature values (lit.8 [R]25 -88.9
D
(c 2.0, CHCl3), lit.10 [R]20D -90.1 (c 2.00, CHCl3)).
Having completed the enantioselective synthesis of PM-
94128 (1), we next turned our attention to the determination
of the absolute stereochemistry of Y-05460M-A (2) through
synthesis. From structural similarity between 1 and 2 as well
as the fact that both 1 and 2 were produced by bacteria of
the same genus, it seemed appropriate to postulate that
Y-05460M-A has the same stereochemical arrangement as
PM-94128 (1). Based on these considerations, we decided to
synthesize stereoisomer 14 as the most probable structure
for Y-05460M-A (Scheme 3). By precisely following the
synthetic sequence used for 1, compound 14 was obtained
uneventfully in 16% overall yield from L-valine-derived
hydroxy lactam 13.12,13,16 The 1H and 13C NMR of 14 were,
as a matter of course, very analogous to those of 1 except for
the signals due to the terminal isopropyl region in its acid
segment part, indicating our synthetic compound to be
undoubtedly 14. Unexpectedly, however, the spectral data
of 14 were considerably different from those reported for
1
natural Y-05460M-A, especially in the H NMR chemical
shifts of the 80-H, 90-H, and 100-H (δ 4.04, 3.31, 2.81 ppm
for 14, respectively; 4.53, 4.26, and 3.21 ppm for natural
Y-05460M-A, respectively).17 Faced with this disagreement,
we suspected that the substantial downfield chemical shifts
for natural Y-05460M-A might be due to its protonation at
the 100-amino group. Thus, we prepared the hydrochloride
of 14 and measured the 1H and 13C NMR spectra of the salt.
(12) Jouin, P.; Castro, B. J. Chem. Soc., Perkin Trans. 1 1987, 1177–1182.
(13) Ma, D.; Ma, J.; Ding, W.; Dai, L. Tetrahedron: Asymmetry 1996, 7,
2365–2370.
Just as we thought, the NMR spectra of 14 HCl were
3
(14) (a) Muramatsu, T.; Yamashita, S.; Nakamura, Y.; Suzuki, M.; Mase,
N.; Yoda, H.; Takabe, K. Tetrahedron Lett. 2007, 48, 8956–8959. (b) Ward,
R. A.; Procter, G. Tetrahedron 1995, 51, 12301–12318.
virtually identical with those of natural Y-05460M-A; the
signals for 80-H, 90-H, and 100-H were, for example, observed
at δ 4.52, 4.25, and 3.20, respectively, in good accordance
with the values for natural Y-05460M-A noted above (see the
Supporting Information for more details). Unfortunately,
(15) Monitoring of the reaction by TLC, together with the 1H NMR
spectrum of the crude reaction product, indicated that the dihydroxylation
proceeded cleanly without formation of any noticeable byproduct, giving 9
as a single stereoisomer. The moderated isolated yield (58%) is, therefore,
considered to be ascribable to the difficulty in the isolation of 9 because of its
high water solubility.
(16) Schmidt, U.; Riedl, B.; Haas, G.; Griesser, H.; Vetter, A.;
Weinbrenner, S. Synthesis 1993, 216–220.
(17) The numbering of 14 follows that of this type of natural products
(see refs 8 and 9).
J. Org. Chem. Vol. 74, No. 19, 2009 7567

Enomoto and Kuwahara
JOCNote
we could not verify that the NMR spectra of the natural
product had actually been recorded as its ammonium salt
because the natural sample of Y-05460M-A was no longer
available. However, the virtually complete agreement of
extract was successively washed with water and brine, dried
(Na2SO4), and concentrated in vacuo. The residue was chromato-
graphed over SiO2 (hexane/EtOAc, 1:0-4:1) to give 56.7 mg
(88%) of 10 as a white crystalline solid: mp 57-58 °C; [R]22
D
1
14 HCl with Y-05460M-A in H and 13C NMR, coupled
þ72.39 (c 1.42, CHCl3); IR νmax 2959 (s), 1788 (s), 1759 (s), 1719
(s) 1151 (s); 1H NMR δ 0.99 (3H, d, J = 6.5 Hz), 1.03 (3H, d, J =
6.5 Hz), 1.26 (1H, ddd, J= 16.0, 9.5, 4.0 Hz), 1.38 (3H, s), 1.46
(3H, s), 1.55 (9H, s), 1.62 (1H, ddd, J = 13.5, 9.5, 2.8 Hz)
1.71-1.81 (1H, m), 4.18 (1H, dd, J = 11.0, 2.8 Hz) 4.38 (1H, d,
J = 5.5 Hz), 4.66 (1H, d, J=5.0 Hz); 13C NMR δ 21.5, 23.5, 25.0,
25.7, 27.0, 27.9, 41.6, 58.8, 75.8, 83.5, 112.6, 149.4, 170.9; HRMS
(FAB) m/z calcd for C16H28O5N ([M þ H]þ) 314.1964, found
314.1967.
3
with the stereochemical uniformity of this class of natural
products,1d,4,6b,7,10 would be enough for concluding the
structure of Y-05460M-A to be 14.
In conclusion, the enantioselective total synthesis of PM-
94128 (1) was accomplished in 14% overall yield from N-
Boc-L-leucine (7) by the concise nine-step sequence of reac-
tions. The synthesis of its one-carbon lower homologue 14
was also achieved by the same approach from N-Boc-
L-valine in 11% overall yield, which, through NMR spectral
comparison, enabled us to assign the stereochemistry of
Y-05460M-A as depicted in 14. Our efficient approach to
PM-94128 (1) and Y-05460M-A (14) would readily be
applicable to the synthesis other members of this type of
natural products simply by changing the starting amino
acid.
(4S,5S)-5-[(1S)-1-tert-Butoxycarbonylamino-3-methylbutyl]-
2,2-dimethyl-1,3-dioxolane-4-carboxylic Acid (11). To a stirred
solution of 10 (35.7 mg, 0.123 mmol) in THF/water (4:1, 2.5 mL)
were added LiOH H2O (14.4 mg, 0.342 mmol) and a drop of
3
30% aq H2O2 at 0 °C. After 40 min, the mixture was quenched
with 5% aq acetic acid and then extracted with EtOAc. The
extract was washed with brine, dried (Na2SO4), and concen-
trated in vacuo to give crude 11 (37.7 mg), which was employed
directly in the next step without further purification.
Amide 12. To a stirred solution of HBTU (43.2 mg, 0.114
mmol) and Et3N (40 μL, 0.285 mmol) in CH2Cl2/DMF (10:3, 2.6
mL) were added a solution of 3 HCl (ca. 0.095 mmol, see the
Experimental Section
3
Supporting Information) in CH2Cl2/DMF (2.5:1, 1.05 mL) and
a solution of crude 11 (37.7 mg) in CH2Cl2/DMF (1.05 mL,
2.5:1) at -15 °C under Ar. After 5.5 h, the mixture was quenched
with water and extracted with Et2O. The extract was succes-
sively washed with water and brine, dried (Na2SO4), and con-
centrated in vacuo. The residue was chromatographed over SiO2
(hexane/EtOAc, 2:1) to give 32.7 mg (60%) of 12 as a white
tert-Butyl
(S)-2,5-Dihydro-2-isobutyl-5-oxo-1H-pyrrole-1-
carboxylate (6). To a stirred solution of 8 (140 mg, 0.546 mmol)
in CH2Cl2 (4.5 mL) were added MsCl (72 μL, 0.928 mmol) and
Et3N (228 μL, 1.637 mmol) at 0 °C under N2, and the mixture
was stirred for 1 h at rt. DBU (122 μL, 0.818 mmol) was then
added, and the resulting mixture was stirred for 40 min. The
mixture was poured into saturated aq NH4Cl at 0 °C and
extracted with Et2O. The extract was successively washed with
water and brine, dried (MgSO4), and concentrated in vacuo to
give 129 mg (99%) of 6 as a colorless oil: [R]22D þ140.3 (c 2.89,
CHCl3); IR νmax 2959 (m), 1774 (s), 1737 (s), 1713 (s), 1314 (s);
1H NMR δ 0.96 (3H, d, J = 6.5 Hz), 1.00 (3H, d, J = 6.5 Hz),
1.43 (1H, ddd, J = 13.5, 10.3, 4.5 Hz), 1.64-1.75 (1H, m), 1.99
(1H, ddd, J = 13.5, 9.5, 3.0 Hz), 4.61 (1H, dt, J = 10.3, 1.5 Hz),
powder: mp 85-86 °C; [R]22 -72.6 (c 0.88, MeOH); IR νmax
D
1
3360 (m), 2955 (m), 1702 (br s); H NMR (acetone-d6) δ 0.90
(3H, d, J=6.5 Hz), 0.92 (3H, d, J=7.0 Hz), 0.98 (6H, d, J =7.0
Hz), 1.15-1.24 (1H, m), 1.35 (3H, s), 1.40 (9H, s), 1.52 (3H, s),
1.60 (1H, ddd, J=13.5, 7.5, 5.5 Hz), 1.65-1.82 (4H, m), 2.85
(1H, dd, J=16.0, 2.5 Hz), 2.97 (1H, dd, J=16.0, 12.3 Hz), 3.88
(3H, s), 4.01-4.09 (1H, m), 4.29-4.37 (1H, m), 4.51 (1H, dd,
J = 7.5, 4.0 Hz), 4.55 (1H, dd, J=12.3, 2.0 Hz), 4.66 (1H, d, J =
7.5 Hz), 5.76 (1H, br s), 6.91 (1H, d, J = 7.5 Hz), 7.04 (1H, d, J =
6.10 (1H, dd, J = 6.3, 1.5 Hz), 7.23 (1H, dd, J = 6.3, 1.5 Hz); 13
NMR δ 22.0, 23.8, 25.0, 28.0, 41.0, 61.3, 82.7, 126.1, 149.1,
150.6, 169.3; HRMS (EI) m/z calcd for C13H21O3N (Mþ)
239.1521, found 239.1528.
C
8.5 Hz), 7.14 (1H, d, J=10.0 Hz), 7.51 (1H, t, J = 8.0 Hz); 13
C
NMR δ 23.1, 24.2, 24.7, 25.5, 26.2, 26.7, 26.8, 28.3, 30.0, 33.6,
40.5, 42.5, 50.9, 57.6, 78.2, 79.9, 80.7, 82.3, 111.1, 113.2, 115.9,
121.7, 136.6, 144.6, 162.7, 163.3, 171.8; HRMS (FAB) m/z calcd
for C31H47O8N2 ([M - H]-) 575.3332, found 575.3336.
PM-94128 (1). To a stirred solution of 12 (11.8 mg, 0.0205
mmol) in CH2Cl2 (2.0 mL) was added a solution of BBr3 in
CH2Cl2 (1.0 M, 307 μL, 0.307 mmol) at -78 °C under Ar. The
mixture was gradually warmed to rt over 4 h. The reaction was
quenched with saturated aq NaHCO3 at 0 °C and extracted with
CHCl3. The extract was washed with brine, dried (Na2SO4), and
concentrated in vacuo. The residue was chromatographed over
SiO2 (CHCl3/MeOH, 40:1) to give 5.8 mg (67%) of 1 as a white
powder: mp 160-161 °C; [R]22D -94.1 (c 0.195, CHCl3); IR νmax
3380 (br s), 2956 (s), 1672 (s); 1H NMR δ 0.91 (3H, d, J = 6.0
Hz), 0.95 (3H, d, J=6.5 Hz), 0.98 (6H, t, J=7.0 Hz), 1.16 (1H,
ddd, J = 14.0, 11.0, 4.0 Hz), 1.49 (1H, ddd, J=13.5, 9.0, 5.0 Hz),
1.58-1.69 (1H, m), 1.70-1.80 (1H, m), 1.82-1.90 (2H, m), 2.83
(1H, dd, J = 16.3, 2.5 Hz), 2.94 (1H, ddd, J=11.0, 8.5, 2.5 Hz),
3.09 (1H, dd, J = 16.3, 12.8 Hz), 3.25 (1H, t, J = 8.5 Hz), 4.08
(1H, d, J=8.0 Hz), 4.36 (1H, ddd, J=10.0, 9.5 4.5 Hz), 4.62 (1H,
d, J =12.8 Hz), 6.70 (1H, d, J = 7.0 Hz), 6.88 (1H, d, J=9.0 Hz),
7.41 (1H, t, J = 8.0 Hz), 7.43 (1H, d, J = 9.5 Hz); 13C NMR δ
21.0, 21.9, 23.1, 23.5, 24.0, 24.8, 30.3, 40.5, 44.2, 48.6, 55.1, 73.6,
74.8, 81.0, 108.1, 116.2, 118.2, 136.5, 139.4, 162.1, 169.5, 175.3;
HRMS (FAB) m/z calcd for C22H35O6N2 ([M þ H]þ) 423.2495,
found 423.2497.
tert-Butyl (2S,3S,4S)-3,4-Dihydroxy-2-isobutyl-5-oxo-1-pyr-
rolidinecarboxylate (9). To a stirred solution of 6 (150 mg,
0.627 mmol) in water/acetone/acetonitrile (1:1:1, 4.5 mL) were
added NMO (147 mg, 1.25 mmol) and a catalytic amount of
OsO4 at rt, and the mixture was stirred for 32 h at rt. Saturated
aq Na2S2O3 was then added, and the resulting mixture was
extracted with CHCl3. The extract was successively washed with
saturated aq Na2S2O3 and brine, dried (MgSO4), and concen-
trated in vacuo. The residue was chromatographed over SiO2
(hexane/EtOAc, 2:1-1:4) to give 99.7 mg (58%) of 9 as a white
crystalline soild: mp 65-66 °C; [R]22D þ18.0 (c 0.52, MeOH); IR
ν
max 3430 (br s), 2957 (s), 1782 (s), 1719 (s); 1H NMR δ 0.98 (3H,
d, J = 6.5 Hz), 1.02 (3H, d, J = 6.5 Hz), 1.35 (1H, ddd, J = 13.5,
11.0, 4.5 Hz), 1.50-1.58 (1H, m), 1.54 (3H, s), 1.69-1.80 (1H,
m), 2.77 (1H, br s), 3.11 (1H, br s), 4.11 (1H, dd, J = 11.5, 3.5
Hz), 4.21 (1H, d, J = 4.5 Hz), 4.39 (1H, d, J = 4.5 Hz); 13C
NMR δ 21.7, 23.5, 25.6, 28.0, 40.0, 61.6, 69.1, 71.0, 83.7, 149.4,
173.5; HRMS (EI) m/z calcd for C13H23O5N (Mþ) 273.1576,
found 273.1581.
tert-Butyl (3aS,6S,6aS)-Tetrahydro-6-isobutyl-2,2-dimethyl-
4-oxo-5H-1,3-dioxolo[4,5-c]pyrrole-5-carboxylate (10). To a
stirred solution of 9 (64.3 mg, 0.235 mmol) in 2,2-dimethoxy-
propane (2.0 mL) was added TsOH H2O (4.5 mg, 0.024 mmol)
at rt under N2. After 50 min, the mixture was poured into
3
saturated aq NaHCO3 at 0 °C and extracted with Et2O. The
7568 J. Org. Chem. Vol. 74, No. 19, 2009

Enomoto and Kuwahara
JOCNote
Acknowledgment. We are grateful to Astellas Pharma, Inc.,
Y-05460M-A (14):. white powder; mp 55-56 °C; [R]22D -63.5
(c 0.055, CHCl3); IR νmax 3385 (br s), 1677 (br s), 1462 (s); 1H
NMR δ 0.84 (3H, d, J=7.0 Hz), 0.92 (3H, d, J=7.0 Hz), 0.96
(3H, d, J = 6.5 Hz), 0.98 (3H, d, J = 7.0 Hz), 1.42-1.74 (2H, m),
1.85 (1H, dd, J=14.0, 10.5, 6.0 Hz), 2.32-2.41 (1H, m), 2.81
(1H, dd, J = 9.0, 2.8 Hz), 2.83 (1H, dd, J=16.0, 2.5 Hz), 3.08
(1H, dd, J=16.0, 13.5 Hz), 3.31 (1H, t, J=9.0 Hz), 4.04 (1H, d,
J = 8.5 Hz), 4.31-4.39 (1H, m), 4.63 (1H, d, J = 12.5 Hz), 6.70
(1H, d, J=7.5 Hz), 6.84 (1H, d, J = 8.5 Hz), 7.41 (1H, d, J = 8.0
Hz), 10.84 (1H, br s); 13C NMR δ 13.5, 19.3, 21.9, 23.0, 24.8,
27.0, 30.3, 40.4, 48.5, 61.3, 70.7, 74.8, 80.9, 108.1, 116.2, 118.2,
136.5, 139.4, 162.2, 169.5, 175.6; HRMS (EI) m/z calcd for
C21H32O6N2 (Mþ) 408.2260, found 408.2259.
1
for providing the H NMR spectrum of Y-05460M-A. This
work was financially supported, in part, by a Grant-in-Aid for
Scientific Research (B) from the Ministry of Education, Cul-
ture, Sports, Science and Technology, Japan (No. 19380065).
Supporting Information Available: Characterization data
and NMR spectra for Y-05460M-A synthetic intermediates,
experimental procedure for 3 HCl, and comparison of NMR
data among 14, 14 HCl, and natural Y-05460M-A. This ma-
3
3
terial is available free of charge via the Internet at http://pubs.
acs.org.
J. Org. Chem. Vol. 74, No. 19, 2009 7569