Synthesis of triketide δ-lactones

Article abstract of DOI:10.1055/s-2001-17514

An efficient synthetic route was developed to prepare substituted δ-lactones 1 and 2 in enantiopure forms which are potentially useful for biosynthetic studies with genetically engineered modular polyketide synthase (PKS). The key step to prepare the targ

Full text of DOI:10.1055/s-2001-17514

1790
PAPER
Synthesis of Triketide d-Lactones
Synthesis of
a
T
a
riketide
d
-L
n
actones g-Jung Kim,a Han-Young Kang,*a David H. Shermanb
Department of Chemistry, Chungbuk National University, Cheongju, Chungbuk 361-763, Korea
b
Department of Microbiology and Biological Process Technology Institute, University of Minnesota, Minneapolis, Minnesota 55455,
USA
Fax +82(43)2672279; E-mail: hykang@chungbuk.ac.kr
Received 23 March 2001; revised 15 June 2001
OH
Abstract: An efficient synthetic route was developed to prepare
substituted d-lactones 1 and 2 in enantiopure forms which are po-
tentially useful for biosynthetic studies with genetically engineered
modular polyketide synthase (PKS). The key step to prepare the tar-
get epimeric lactones involves the samarium(II) iodide-mediated
Reformatsky reaction.
O
O
O
M
O
OR
O
1
+
OH
Xc
Key words: polyketide biosynthesis, lactones, samarium(II) io-
dide, aldol reaction, Reformatsky reaction
A
B
O
2
Modular polyketide synthases (PKSs) are giant multien-
zyme complexes to produce structurally diverse natural
products by successive cycles of chain extension.1 ‘Non-
natural’ natural products from the hybrid modular PKSs
have attracted much attention in connection with natural
product drug discovery and development by so-called
‘Combinatorial Biosynthesis’. Smaller hybrid PKS sys-
tems such as DEBS1 (DEBS = 6-deoxyerythronolide B
synthase)+TE (thioesterase),2 or DEBS1–TE3 truncated
versions of the erythromycin PKS, both of which contain-
ing the first two modules of 6-deoxyerythronolide B fused
to the TE domain, have been extensively utilized in order
to facilitate the detailed investigations on the biosynthesis
of 6-deoxyerythronolide B. These hybrid PKSs are re-
sponsible for producing smaller lactones.4
Scheme 1
propionate oxazolidinone 3 to produce the required two
stereogenic centers. After protection of the OH group, re-
duction to remove the chiral auxiliary followed by the
Swern oxidation gave the desired known aldehyde 7 in
good yield overall.4f
Ph
Ph
1)Bu2BOTf,
Et3N
2) CH3CH2CHO
O
O
OR
N
N
O
O
(73%)
O
O
In connection with the generation of hybrid PKSs derived
from the pikromycin PKS system,5 we are interested in the
following d-lactones 1 and 2. The synthesis of these lac-
tones would facilitate the identification and isolation of
the lactones produced by hybrid PKSs. Herein, we wish to
report a successful and practical synthetic route to prepare
both enantiopure lactones 1 and 2 utilizing aldol and the
Reformatsky reactions as key synthetic steps to secure the
desired stereochemical relationships. Although both lac-
tones has been reported to be isolated in connection with
the study on the bimodular polyketide synthase based on
domain or modular exchanges, they have not been chem-
ically prepared yet.6
3
4 R=H
TBDMSCl,
imidazole,
DMF (94%)
5 R=TBDMS
LiBH4,
H2O
(76%)
(COCl)2,
DMSO;
Et3N (98%)
O
OTBDMS
OH OTBDMS
7
6
Scheme 2
Synthesis of both lactones could be achieved by coupling
between the fragments A and B shown in the retrosynthet-
ic scheme (Scheme 1). The synthetic scheme for the alde-
hyde fragment (Scheme 2) is quite straightforward and
involves boron enolate aldol reaction7 with the known
Acetate aldol reaction was the next crucial step to estab-
lish the stereochemistry of the 3-hydroxyl group in the de-
sired lactones. Acetate aldol condensations has been
known to offer low diastereoselectivity with chiral eno-
lates derived from a-acetyl oxazolidinones. The simple
adaptation of boron enolate aldol strategy under the iden-
tical conditions described in Scheme 2 provided a mixture
of products that was not easy to separate.
Synthesis 2001, No. 12, 25 09 2001. Article Identifier:
1437-210X,E;2001,0,12,1790,1793,ftx,en;F02801SS.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0039-7881

PAPER
Synthesis of Triketide d-Lactones
1791
There have been several methods available in the litera- lactone 2. The 1H NMR spectral data of the lactone 2 com-
ture to achieve the acetate aldol reaction efficiently such pletely matched with those reported in the literature, ob-
as Nagao’s chiral 1,3-thiazolidine-2-thione technology8 tained from the compound isolated from the culture with
and the method via titanium enolates.9 Recently utiliza- the mutant strain producing a hybrid PKS protein.12
tion of the Reformatsky reaction to resolve acetate aldol
reactions has been reported. For example, the chromium
The epimeric lactone 1 could be more efficiently prepared
starting from the enantiomeric (S)-oxazolidinone 11 as
shown in Scheme 4.
Reformatsky reaction has been applied to produce stereo-
genic carbon centers.6a,10 We looked for milder and easier
methods to generate the desired stereochemistry of the hy-
droxyl group. Samarium(II) iodide has been known as a
Ph
Ph
n-BuLi,
very versatile reagent for numerous organic transforma-
tions. We were interested in the samarium(II) iodide-me-
diated asymmetric Reformatsky-type reaction,11 which
was recently reported to be efficient. The synthetic
scheme to prepare the desired lactones is shown in
Scheme 3.
O
BrCH2COBr
(75%)
NH
O
N
O
O
Br
O
12
11
SmI2, –78 °C, then 7
(13a–13b=1:1) (75%)
Ph
Ph
n-BuLi,
BrCH2COBr
(71%)
Ph
Ph
O
O
OH
OTBDMS
O
OH
OTBDMS
NH
O
N
N
N
+
O
O
Br
O
O
O
O
O
9
8
13a
13b
SmI2, -78oC, then 7
(10a–10b=25:1) (94%)
1) H2O2, LiOH, THF–H2O=4:1
2) HCl(1M)–THF=5:1(v/v), 40 °C
(60%)
(76%)
Ph
Ph
O
OH
OTBDMS
O
OH
OTBDMS
OH
OH
N
N
+
O
O
O
O
O
O
O
O
10a
10b
1
2
1) H2O2, LiOH, THF:H2O=4:1
2) HCl(1M)–THF=5:1(v/v), 40oC
(78%)
Scheme 4
The chiral bromoacetyloxazolidinone 12, prepared under
the same reaction condition described before, was subject-
ed to the samarium(II) iodide-mediated Reformatsky re-
action. In this case the diastereoselectivity of the two
possible isomers 13a and 13b was low and an 1:1 ratio of
the two diastereoisomers was observed presumably due to
the mismatched pair relationship of the chiral enolate and
the aldehyde used. This could be, however, used as an ad-
vantage since eventually we need to prepare both isomers.
After separation, both isomers were successfully convert-
ed to the desired lactones 1 and 2. For comparison, we per-
formed the same Reformatsky reaction with ethyl
bromoacetate and a 6:1 ratio of the corresponding two iso-
mers [compared to the 25:1 ratio (10a:10b) from the
matched pair] was obtained; this is due to the intrinsic se-
lectivity originating from the aldehyde. Therefore, the 1:1
ratio of the two diasteromers was not impressive, but it
was the best selectivtity attainable with the Evans’ auxil-
iary for the lactone 1.
OH
O
O
2
Scheme 3
Bromoacetyloxazolidinone 9 was easily prepared from
the commercially available (R)-oxazolidinone 8. The key
Reformatsky reaction mediated by samarium(II) iodide
was performed at –78 °C to give the desired condensation
products in a highly diastereoselective fashion (25:1
based on isolated yields after separation) in favor of 10a.
The stereochemistry of the major product 10a was pre-
dicted by the model proposed.11 We found that this samar-
ium(II) iodide-mediated Reformatsky reaction was
efficient and easy to perform. Conversion of the conden-
sation product 10a to the lactone has been carried out by
hydrolysis to a free acid, which was subjected to acid-cat-
alyzed lactonization without isolation to give the target
In summary, we have successfully developed synthetic
routes to the substituted d-lactones. The samarium(II) io-
dide-mediated Reformatsky reaction was successfully
Synthesis 2001, No. 12, 1790–1793 ISSN 0039-7881 © Thieme Stuttgart · New York

1792
S.-J. Kim et al.
PAPER
MS (EI): m/z (%) = 449 (M+), 402, 392, 374, 334, 300, 252, 225,
215, 197, 178, 123, 99, 91, 71, 57(100).
employed to establish the stereochemistry of the carbon
center bearing the hydroxyl group for both epimers. This
whole sequence could be used as an access to compounds HRMS: m/z Calcd for C24H39NO5Si: 449.2598. Found: 449.2591.
derived from bimodular or trimodular PKSs.
13a
IR (film): 1785 (C=O), 1698, 1387 cm–1.
1H NMR and 13C NMR spectra were recorded on a Bruker AM300
1H NMR (300 MHz, CDCl3): d = 7.13–7.28 (m, 5 H, C6H5), 4.62 (m,
and Brucker AM400 spectrometers. The chemical shifts (d) are re-
1 H, NCH), 4.20 (m, 1 H, CHOH), 4.12 (m, 2 H, NCHCH2O), 3.69
ported in ppm downfield from TMS. IR specta were recorded on
(m, 1 H, CHOSi), 3.24 (dd, 1 H, J = 13.4, 3.1 Hz, CHHC6H5), 3.16
IFS-66/S spectrophotometer. Optical rotations were measured us-
[dd, 1 H, J = 16.9, 9.2 Hz, CHH(C=O)], 2.98 [dd, 1 H, J = 16.8, 3.5
ing a Jasco DIP-1000 digital polarometer in solution in a 1 dm cell.
Hz, CHH(C=O)], 2.70 [dd, 1 H, J = 13.3, 9.6 Hz, CHHC6H5), 1.59
MS and HRMS were obtained on a VG Autospec Ultma GC/MS
(m, 1 H, CHCH3), 1.48 (m, 2 H, CH2CH3), 0.89 (d, 3 H, J = 6.9 Hz,
system using direct insertion probe (DIP) and electron impact (EI,
CHCH3), 0.81 [s, 9 H, SiC(CH3)3], 0.76 (t, 3 H, J = 7.5 Hz,
70eV) methods. Compounds 9 and 12 were prepared based on a
CH2CH3), 0.00 [s, 6 H, Si(CH3)2].
standard acylation procedure. The aldehyde 7 was synthesized ac-
13C NMR (100 MHz, CDCl3): d = 172.5, 153.5, 135.2, 129.4, 129.0,
127.3, 70.1, 66.2, 55.1, 41.2, 40.5, 37.7, 27.0, 25.9, 18.0, 9.8, 7.6,
–3.9, –4.5.
MS (EI): m/z (%) = 449 (M+), 402, 392, 374, 334, 316, 300,
252(100), 234, 225, 215, 197, 174, 157, 143, 133, 123, 99, 91, 77,
59.
cording to the literature.4f
(4R,3’S,4’R,5’R)-4-Benzyl-3-[5’-(tert-butyldimethylsilyloxy)-3’-
hydroxy-4’-methylheptanoyl]-2-oxazolidinone 10a and
(4R,3’R,4’R,5’R)-4-Benzyl-3-[5’-(tert-butyldimethylsilyloxy)-3’-
hydroxy-4’-methylheptanoyl]-2-oxazolidinone 10b; Typical
Procedure
HRMS: m/z Calcd for C24H39NO5Si: 449.2598. Found: 449.2597.
CH2I2 (161 mL, 2.00 mmol) was added to a suspension of samarium
powder (331 mg, 2.20 mmol) in THF (20 mL) under N2 and stirred
for 2 h. The resulting greenish blue solution was cooled to –78 °C.
To this solution was added a solution of (4R)-4-benzyl-3-(2’-bro-
moacetyl)-2-oxazolidinone (9; 298 mg, 1.0 mmol) and (2R, 3R)-3-
(t-butyldimetylsilyloxy)-2-methylpentanal (7; 242 mg, 1.05 mmol)
in THF (3.0 mL) at –78 °C. After stirring for 1 h at –78 °C, the so-
lution was warmed to r.t. and 0.1 M of HCl (25 mL) was added. The
resulting solution was extracted with Et2O (3 ¥ 30 mL). The organic
layer was washed with aq Na2S2O3 and brine, dried (MgSO4) and
then concentrated. The residue was purified by flash chromatogra-
phy (hexane–EtOAc, 3:1) to give 10a (405 mg, 90%) and 10b (16
mg, 4%) as yellowish oils.
13b
IR (film): 1785 (C=O), 1698, 1388 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.13–7.25 (m, 5 H, C6H5), 4.63 (m,
1 H, NCH), 4.12 (m, 3 H, NCHCH2O and CHOH), 3.73 (m, 1 H,
CHOSi), 3.24 (dd, 1 H, J = 13.3, 3.0 Hz, CHHC6H5), 3.01 [m, 2 H,
CH2(C=O)], 2.68 (dd, 1 H, J = 13.3, 9.7 Hz, CHHC6H5), 1.73 (m,
1 H, CHCH3), 1.52 (m, 2 H, CH2CH3), 0.85 (d, 3 H, J = 7.2 Hz,
CHCH3), 0.81 [s, 9 H, SiC(CH3)3], 0.78 (t, 3 H, J = 7.1 Hz,
CH2CH3), 0.03 (s, 3 H, SiCH3), 0.00 (s, 3 H, SiCH3).
13C NMR (100 MHz, CDCl3): d = 172.1, 153.5, 135.3, 129.4, 128.9,
127.3, 70.1, 66.2, 55.3, 42.2, 41.5, 37.9, 25.8, 25.2, 18.0, 12.3, 11.0,
–4.5.
10a
MS (EI): m/z (%) = 449 (M+), 402, 374, 334, 300, 252, 225, 215,
197, 178, 145, 133(100), 117, 99, 91, 73, 57.
IR (film): 1780 (C=O), 1699, 1389 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.11–7.27 (m, 5 H, C6H5), 4.61 (m,
1 H, NCH), 4.24 (m, 1 H, CHOH), 4.11 (m, 2 H, NCHCH2O), 3.70
(m,1 H, CHOSi), 3.21 (dd, 1 H, J = 13.4, 3.1 Hz, CHHC6H5), 3.10
[dd, 1 H, J = 16.9, 9.2 Hz, CHHC(=O)], 2.98 [dd, 1 H, J = 16.8, 3.2
Hz, CHH(C=O)], 2.69 (dd, 1 H, J = 13.3, 9.6 Hz, CHHC6H5), 1.59
(m, 1 H, CHCH3), 1.48 (m, 2 H, CH2CH3), 0.88 (d, 3 H, J = 6.9 Hz,
CHCH3), 0.80 [s, 9 H, SiC(CH3)3], 0.75 (t, 3 H, J = 7.5 Hz,
CH2CH3), 0.01 (s, 3 H, SiCH3), 0.00 (s, 3 H, SiCH3).
13C NMR (100 MHz, CDCl3): d = 172.3, 153.4, 135.2, 129.4, 129.0,
127.3, 70.2, 66.2, 55.1, 41.2, 40.2, 37.9, 27.1, 25.8, 18.0, 9.8, 7.3,
–3.6, –4.6.
MS (EI): m/z (%) = 449 (M+), 402, 392, 374, 300, 276, 259, 215,
171, 141, 117, 73, 57(100).
HRMS: m/z Calcd for C24H39NO5Si: 449.2598. Found: 449.2608.
(4S,5R,6R)-6-Ethyl-4-hydroxy-5-methyltetrahydropyran-2-one
2 and (4R,5R,6R)-6-Ethyl-4-hydroxy-5-methyltetra-
hydropyran-2-one 1; Typical Procedure
To a solution of 10a (113 mg, 0.25 mmol) in THF–H2O (1.25 mL,
4:1) was added dropwise 30% aq H2O2 (1.50 mmol, 170 mL) and an
aq solution of LiOH (15 mg, 0.63 mmol) in H2O (630 mL) at 0 °C.
After strirring for 10 min, the solution was warmed to r.t. and stirred
for 1 h. The reaction was quenched by the addition of 10% aq
Na2SO3 solution (1.5 mL) and then THF was removed by evapora-
tion. The solution was cooled to 0 °C and acidified (pH 1) by the ad-
dition of 6 M HCl. After extraction with EtOAc (5 ¥ 20 mL), drying
(MgSO4), and concentration, 1 M HCl–THF (6 mL, 5:1) was added
and the resulting mixture was stirred for 2 h at 40 °C. The solution
was extracted with EtOAc (3 ¥ 20 mL) and washed with brine. The
organic layer was dried (MgSO4) and concentrated. Flash chroma-
tography (hexane–EtOAc, 1:2) provide the lactone 2 as a yellowish
oil (31 mg, 78%).
HRMS: m/z Calcd for C24H39NO5Si: 449.2598. Found: 449.2584.
10b
IR (film) 1784 (C=O), 1698, 1388 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.07–7.27 (m, 5 H, C6H5), 4.63 (m,
1 H, NCH), 4.10 (m, 3 H, NCHCH2O and CHOH ), 3.76 (m,1 H,
CHOSi), 3.23 (dd, 1 H, J = 13.4, 3.0 Hz, CHHC6H5), 2.73 (dd, 1 H,
J = 13.4, 9.4 Hz, CHHC6H5), 3.03 [m, 2 H, CHH(C=O)], 1.71 (m,
1 H, CHCH3), 1.49 (m, 2 H, CH2CH3), 0.86 (d, 3 H, J = 7.7 Hz,
CHCH3), 0.81 [s, 9 H, SiC(CH3)3], 0.77 (t, 3 H, J = 7.0 Hz,
CH2CH3), 0.04 (s, 3 H, SiCH3), 0.00 (s, 3 H, SiCH3).
13C NMR (100 MHz, CDCl3): d = 172.4, 153.5, 135.2, 129.5, 129.0,
127.3, 70.1, 66.1, 55.1, 42.1, 41.6, 37.7, 25.8, 25.5, 18.0, 11.8, 10.9,
–4.5.
2
[a]D26.1 +80.5 (c = 0.51, CHCl3).
IR (film): 3426, 1713 (C=O), 1254 cm–1.
1H NMR (300 MHz, CDCl3): d = 4.62 (m, 1 H, H-6), 4.06 (m, 1 H,
H-4), 2.81 [dd, 1 H, J = 18.3, 5.3 Hz, CHH(C=O)], 2.55 [dd, 1 H,
J = 18.3, 2.7 Hz, CHH(C=O)], 2.17 (br, 1 H, CHOH), 1. 96 (m, 1 H,
H-5), 1,78 (ddq, 1 H, J = 14.2, 7.2, 7.3 Hz, CHHCH3), 1.55 (ddq,
Synthesis 2001, No. 12, 1790–1793 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Synthesis of Triketide d-Lactones
1793
1 H, J = 13.9, 7.2, 7.0 Hz, CHHCH3), 1.02 (t, 3 H, J = 7.4 Hz,
CH2CH3), 0.93 (d, 3 H, J = 7.2 Hz, CHCH3).
(2) Kao, C. M.; Luo, G.; Katz, L.; Cane, D. E.; Khosla, C. J. Am.
Chem. Soc. 1995, 117, 9105.
(3) Cortés, J.; Wiesmann, K. E. H.; Roberts, G. A.; Brown, M.
J. B.; Staunton, J.; Leadlay, P. F. Science 1995, 268, 1487.
(4) (a) Kao, C. M.; Luo, G.; Katz, L.; Cane, D. E.; Khosla, C. J.
Am. Chem. Soc. 1994, 116, 11612. (b) Brown, M. J. B.;
Cortés, J.; Cutter, A. L.; Leadlay, P. F. J. Chem. Soc., Chem.
Commun. 1995, 1517. (c) Wiesmann, K. E. H.; Cortés, J.;
Brown, M. J. B.; Cutter, A. L.; Staunton, J.; Leadlay, P. F.
Chem. Biol. 1995, 2, 583. (d) Piper, R.; Ebert-Khosla, S.;
Cane, D. E.; Khosla, C. Biochemistry 1996, 35, 2054.
(e) Luo, G.; Pieper, R.; Rosa, A.; Khosla, C.; Cane, D. E.
Bioorg. Med. Chem. 1996, 4, 995. (f) Wilkinson, A. L.;
Hanefeld, U.; Wilkinson, B.; Leadlay, P. F.; Staunton, J.
Tetrahedron Lett. 1998, 39, 9827.
(5) Xue, Yongquan.; Sherman, D. H. Nature 2000, 403, 571.
(6) (a) Ranganathan, A.; Timoney, M.; Bycroft, M.; Cortés, J.;
Thomas, I. P.; Wilkinson, B.; Kellenberger, L.; Hanefeld,
U.; Galloway, I. S.; Stanton, J.; Leadlay, P. F. Chem. Biol.
1999, 6, 731. (b) Lau, J.; Fu, H.; Cane, D. E.; Khosla, C.
Biochemistry 1999, 38, 1643.
13C NMR (100 MHz, CDCl3): d = 170.8, 79.6, 68.5, 36.8, 35.7, 24.9,
10.1, 10.0.
MS (EI): m/z (%) = 158 (M+), 141(100), 123, 111, 99, 95, 82, 70,
58, 55.
HRMS: m/z Calcd for C8H14O3: 158.0943. Found: 158.0944.
1
[a]D25.7 +72.3 (c = 0.47, CHCl3).
IR (film): 3428, 1719 (C=O), 1240 cm–1.
1H NMR (300 MHz, CDCl3): d = 4.24 (ddd, 1 H, J = 10.6, 6.6, 4.3
Hz, H-4), 4.13 (m, 1 H, H-6), 2.87 [dd, 1 H, J = 18.3, 6.9 Hz,
CHH(C=O)], 2.48 [dd, 1 H, J = 18.3, 10.5 Hz, CHH(C=O)], 2.17
(m, 1 H, H-5), 1.84 (ddq, 1 H, J = 14.2, 7.1, 7.3 Hz, CHHCH3), 1.75
(br, 1 H, CHOH), 1.59 (ddq, 1 H, J = 14.0, 7.1, 7.0 Hz, CHHCH3),
1.01 (t, 3 H, J = 7.4 Hz, CH2CH3), 0.95 (d, 3 H, J = 7.1 Hz, CHCH3).
13C NMR (100 MHz, CDCl3): d = 170.4, 82.2, 67.1, 36.2, 35.3, 25.2,
9.92, 3.82.
MS (EI): m/z (%) = 158 (M+), 149, 141, 129, 116, 111, 100, 91, 86,
82, 77, 71, 65, 62, 58(100), 55, 49.
(7) Gage, J. R.; Evans, D. A. Org. Synth. 1990, 68, 83.
(8) Nagao, Y.; Hagiwara, Y.; Kumagai, T.; Ochiani, M.; Inoue,
T.; Haimoto, K.; Fujita, E. J. Org. Chem. 1986, 51, 2391.
(9) Evans, D. A.; Melson, J. V.; Taber, T. R. J. Am. Chem. Soc.
1981, 103, 3099.
HRMS: m/z Calcd for C8H14O3: 158.0943. Found: 158.0945.
(10) (a) Wessjohann, L. S.; Wild, H. Synlett 1997, 731.
(b) Wessjohann, L. S.; Wild, H. Synthesis 1997, 512.
(c) Wessjohann, L. S.; Gabriel, T. J. Org. Chem. 1997, 62,
3772.
(11) (a) Fukuzawa, S.-i.; Matsuzawa, H.; Yoshimitsu, S.-i. J.
Org. Chem. 2000, 65, 1702. (b) Fukuzawa, S.-i.;
Tatsuzawa, M.; Hirano, K. Tetrahedron Lett. 1998, 39,
6899.
Acknowledgements
This work was accomplished with the Research Fund provided by
Korea Research Foundation, Support for Faculty Research Abroad
and also with the financial support of the Center for Molecular De-
sign and Synthesis (CMDS), KAIST.
(12) Ranganathan, A.; Timoney, M.; Bycroft, M.; Cortés, J.;
Thomas, I. P.; Wilkinson, B.; Kellenberger, L.; Hanefeld,
U.; Galloway, I. S.; Stanton, J.; Leadlay, P. F. Chem. Biol.
1999, 6, 731.
References
(1) (a) Hopwood, D. A.; Sherman, D. H. Ann. Rev. Genet. 1990,
24, 37. (b) Cane, D. E.; Walsh, C. T.; Khosla, C. Science
1998, 282, 63.
Synthesis 2001, No. 12, 1790–1793 ISSN 0039-7881 © Thieme Stuttgart · New York