Novel chiral glycerol analogues building blocks. Application to the synthesis of bioactive glycoglycerolipid analogues

Article abstract of DOI:10.1055/s-2001-16789

Monoacylglycosylglycerols show anti-tumor promoting effects: in order to study the role of the ester function we have prepared by simple methods (R)-1-O-benzyl-1,2-decandiol, (R)-3-O-benzyl-1-O-hexyl-sn-glycerol, and (R)-1-O-benzyl-5-oxo-1,2-decandiol; these optically active compounds are building blocks for the synthesis of monohexanoylglycosylglycerol isosters.

Full text of DOI:10.1055/s-2001-16789

LETTER
1379
Novel Chiral Glycerol Analogues Building Blocks. Application to the Synthesis
of Bioactive Glycoglycerolipid Analogues
Patrizia Ferraboschi,* Diego Colombo, Federica Compostella, Shahrzad Reza-Elahi
Dipartimento di Chimica e Biochimica Medica-Via Saldini,50-20133-Milan, Italy
Fax +39-2-58356040; E-mail: Patrizia.Ferraboschi@unimi.it
Received 28 May 2001
(R)-1-O-Benzyldecan-1,2-diol4 7 was obtained in 80%
Abstract: Monoacylglycosylglycerols show anti-tumor promoting
yield from 5 by reaction with 1-heptylmagnesiumbromide
effects: in order to study the role of the ester function we have pre-
and copper (I) bromide-dimethyl sulfide complex; the
pared by simple methods (R)-1-O-benzyl-1,2-decandiol, (R)-3-O-
benzyl-1-O-hexyl-sn-glycerol, and (R)-1-O-benzyl-5-oxo-1,2-de-
same protected epoxyalcohol 5 afforded the desired (R)-
candiol; these optically active compounds are building blocks for hexylether5 8 (70% yield) by reaction with sodium in hex-
anol (Scheme 1).6
the synthesis of monohexanoylglycosylglycerol isosters.
Key words: glycolipids, antitumor agents, isosters, building
blocks, synthons
Monoacylglycosylglycerols have been reported to have
significant anti-tumor promoting effects;1 in particular,
among the different derivatives, compounds 1b and 1c,
both bearing a hexanoyl chain on the glycerol C-1, are the
most active.2,3
In the course of a project aimed at ascertaining the struc-
tural features responsible for the cancer chemopreventing
activity, in order to study the role of the ester function in
modulating this activity, we have planned to prepare the
Scheme 1
acylglucosyl- and galactosylglycerol analogues 2b-c, 3b-
c and 4b-c in which the chain is linked to the glycosylg-
lycerol skeleton through bonds metabolically more stable
than the ester linkage.
In turn, for the synthesis of isoster 9, (R)-lactone 6, after
reaction with benzyl trichloroacetimidate to the corre-
sponding benzylether7 10, was converted into its methyl
ester and protected as silylether giving compound 11.8
LiAlH4 reduction of the ester function, followed by
pyridium chlorochromate (PCC) oxidation afforded (R)-
aldehyde 12,9 which was transformed in secondary alco-
hol 13,10 by treatment with 1-bromopentyl magnesium.
Then, oxidation of 13 with PCC afforded 5-ketone 14, and
deprotection of the silylether with tetrabutylammonium
fluoride (TBAF) in tetrahydrofuran gave compound 911 in
26% overall yield from lactone 6 (Scheme 2).
In this paper, the preparation of compounds 7, 8 and 9,
suitably protected at the primary hydroxy group, i.e. the
proper isosters of 1-O-hexanoyl-sn-glycerol 1a, which are
required for the synthesis of the target compounds by gly-
cosidation at the secondary hydroxyl, is described.
To obtain the compounds with the desired C-2 configura-
tion, the commercially available (R)-benzylglycydol 5
and (R)- -hydroxymethyl- -butyrolactone 6 were chosen
as starting material for the synthesis of alkyl and ether
isosters 2a and 3a or of the carbonylic isoster 4a, respec-
tively.
Since compound 9 is a synthon for the above mentioned
glycosylation reactions, and it is prone to an intramolecu-
lar cyclization reaction to give a six-membered cyclic
Synlett 2001, No. 9, 1379–1382 ISSN 0936-5214 © Thieme Stuttgart · New York

1380
P. Ferraboschi et al.
LETTER
Scheme 2 Reagents: i. Cl3CC( = NH)OCH2Ph, CF3SO2OH, CH2Cl2/ hexane, 0 °C, 0.5h; ii. N NaOH, rt, 1h; iii. CH3I, TBABr,
CH3COCH3, rt, 8h; iv. TBDMSCl, imidazole, THF, rt, 15h; v. LiAlH4,THF, rt, 4h; vi. PCC, AcONa, CH2Cl2, rt, 1h; vii. C5H11MgBr, Et2O,
rt, 4h; viii. PCC, AcONa, CH2Cl2, rt, 1h; ix. TBAF, THF, rt, 8h; x. ethylene glycol, (EtO)3CH, BF3/Et2O, C6H6, reflux, 4h; xi. TBAF, THF,
rt, 8h; xii. HSCH2CH2SH, BF3/Et2O, CH2Cl2, rt, 0.5h.
Scheme 3 Reagents: i. 16, BF3/Et2O, CH2Cl2, 0 °C to rt, 5h; ii. NBS, acetone/H2O, 0 °C; iii. MeONa, MeOH; iv. H2, Pd/C, MeOH/AcOH.
hemiacetal, we protected the carbonyl function by synthe- starting from -D-glucose pentaacetate 18, the corre-
sizing both (R)-ketal 1512,13 and (R)-thioketal 1614 sponding glucoconjugate 2016 was obtained in 65% yield.
(Scheme 2).
After conventional deprotection methods the glycoglycer-
olipid analogues 4b and 4c were recovered17 (Scheme 3).
As an illustration of the applicability of these novel glyc-
erol analogues building blocks, we report the synthesis of In conclusion, we have reported an approach, which pro-
compounds 4b and 4c. Several attempts of glycosylation vides a general access to glycerol analogues building
between ketal 15 and -D-galactose pentaacetate, or the blocks; the described simple synthetic routes for com-
corresponding -trichloroacetimidate, in the presence of pounds 7-9 are, in fact, generalizable to whatever chain
BF3-ethyl etherate, or between 15 and peracetylated meth- lengths and, besides the described synthesis of glycocon-
yl -D-thiogalactopyranoside under dimethyl(methylth- jugates, also appropriate for the obtention of other glycer-
io)sulfonium tetrafluoroborate promotion, resulted in ol containing compounds, as for example, the PAF
very low yields of glycosylation product and decomposi- (platelet antiaggregating factor)18 and the ALP (alkyllyso-
tion of acceptor 15.
phospholipid)19 and their isosters20 in which the 1-position
of the glycerol should be selectively modified.
To circumvent the problem, we successfully turned our at-
tention to thioketal 16; the glycosylation product 1915 was
obtained in 70% yield from 16 and -D-galactose pentaac-
etate 17 in dichloromethane (0 °C to r.t.) in the presence
of BF3-ethyl etherate (1 equiv). Using the same procedure,
Acknowledgement
This work was supported by the Ministero dell’ Università e della
Ricerca Scientifica e Tecnologica (MURST, ex-60%).
Synlett 2001, No. 9, 1379–1382 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
Novel Chiral Glycerol Analogues Building Blocks
1381
3.66 (s, 3H, CH3-O), 3.86-3.92 (m, 1H, CH-O), 4.50-4.52 (m,
2H, CH2Ph), 7.32-7.34 (m, 5H, Ar).
References and Notes
(1) Colombo, D.; Compostella, F.; Ronchetti, F.; Scala, A; Toma,
L.; Kuchide, M.; Tokuda, H.; Nishino, H. Cancer Lett. 2000,
161, 201.
(2) Colombo, D.; Scala, A.; Taino, I.M.; Toma, L.; Ronchetti, F.;
Tokuda, H.; Nishino, H.; Nagatsu, A.; Sakakibara, J. Cancer
Lett. 1998, 123, 83.
(3) Colombo, D.; Compostella, F.; Ronchetti, F.; Scala, A.; Toma,
L.; Mukainaca, T.; Nagatsu, A.; Konoshima, T.; Tokuda, H.;
Nishino, H. Cancer Lett. 1999, 143, 1.
(4) (R)-1-O-Benzyl-1,2-decandiol 7 was prepared as reported for
a similar compound differing in the chain length (Iguchi, K.;
Kitade, M.; Kashiwagi, T.; Yamada, Y. J. Org. Chem. 1993,
58, 5690) in 80% yield from (R)-benzylglycidol 5 (1g,
FLUKA), oil; [ ]D - 4.0 (c 1 in CHCl3). 1H NMR CDCl3,
(9) (R)-5-O-Benzyl-4-O-tert-butyldimethylsilyl-4,5-
dihydroxypentanal 12. Methylester 11 was reduced with
LiAlH4 (r.t., 4 h) in THF to afford the corresponding alcohol
that was oxidized (r.t., 1 h) with pyridinium chlorochromate
(PCC) in presence of sodium acetate in dichloromethane.
Filtration through a Florisil pad and evaporation of the
solvents afforded the aldehyde 12 (70% from 11), oil.
[ ]D+15.8 (c 2 CHCl3). 1H NMR CDCl3, 500MHz): 0.0 (s,
6H, CH3Si), 0.90 (s, 9H, (CH3)3C), 1.76-1.84 (m, 1H, CH-3),
1.88-1.98 (m, 1H, CH-3), 2.48 (t, 2H, CH-2), 3.32 (m, 1H,
CH-OBn), 3.40 (m, 1H, CH-OBn), 3.86-3.92 (m, 1H, CH-O),
4.46-4.50 (m, 2H, CH2Ph), 7.22-7.36 (m, 5H, Ar), 9.74 (s, 1H,
CHO). IR (CHCl3) max 1730 cm-1.
(10) (2R),(5R,S)-1-O-Benzyl-2-O-tert-butyldimethylsilyl-1,2,5-
decantriol 13. Aldehyde 12 was treated with pentyl
magnesium bromide in diethyl ether (r.t., 4 h) to afford the
secondary alcohol 13 in 90% yield. 1H NMR CDCl3,
500 MHz):
0.84 (t, 3H, CH3), 1.20-1.36 (m, 12H, CH2),
1.36-1.50 (m, 2H, CH2-3), 2.50-2.58 (m, 1H, exchang.), 3.27
(m, 1H, CH-OBn), 3.45 (m, 1H, CH-OBn), 3.74-3.82 (m, 1H,
CH-O), 4.50 (s, 2H, CH2Ph), 7.20-7.38 (m, 5H, Ar). m/z (EI)
264 (M+), 246, 217, 181, 173, 143, 122, 91.
500MHz):
0.0 (s, 6H, (CH3)2Si), 0.90-0.98 (m, 12H,
(CH3)3C and CH3), 1.20-1.80 (m, 12H, CH2), 3.32-3.44 (m,
2H, CH2-OBn), 3.52-3.62 (m, 1H, CH-OH), 3.84-3.92 (m, 1H,
CH-O), 4.50 (s, 2H, CH2Ph), 7.20-7.36 (m, 5H, Ar).
(5) (R)-3-O-Benzyl-1-O-hexyl-sn-glycerol 8 was prepared as
described for the analogue 1-methylether (Waagen, V.;
Hollingsaeter, I.; Partali, V.; Thorstad, O.; Anthonsen, T.
Tetrahedron: Asym. 1993, 4, 2265) in 70% yield from 5 (1g),
oil; [ ]D +3.9 (c 1 in CHCl3). 1H NMR CDCl3, 500MHz):
0.90 (t, 3H, CH3), 1.22-1.38 (m, 6H, CH2), 1.52-1.60 (m, 2H,
CH2-CH2-O), 2.76-2.80 (m, 1H, exchang.), 3.38-3.58 (m, 6H,
CH2-O), 3.96-4.00 (m, 1H, CH-O), 4.54 (s, 2H, CH2Ph), 7.22-
7.36 (m, 5H, Ar). m/z (EI) 267 (MH+), 233, 217, 187, 181,
163, 142, 113, 107.
(6) To ascertain whether the high optical purity of the starting
material 5 remained unchanged in the products 7 and 8, 1H
NMR analysis of the MTPA-esters of the corresponding
optically active and racemic compounds was performed
(Dale, J.A.; Mosher, H.S. J. Am. Chem. Soc. 1973, 95, 512).
Racemic 7 and 8 were prepared starting from (R,S)-
benzylglycidol (FLUKA). The MTPA-derivative of racemic 7
showed as significant signals two multiplets centered at 4.40
and 4.48 ppm due to the OCH2Ph protons. In the spectrum of
the MTPA derivative of (R)-7 the signal at 4.40 ppm was not
detectable. In the case of the MTPA derivative of (R,S)-8, the
1H NMR spectrum showed two multiplets centered at 4.42 and
4.52 ppm due to the OCH2Ph protons. The same signals for the
(R)-8 derivative were present in a 2/98 ratio indicating a 96%
ee.
(7) 5-Benzyloxymethyl-dihydrofuran-2-one 10. The benzylation
was carried out with benzyl trichloroacetimidate in presence
of trifluoromethanesulphonic acid (Nicolaou, K.C.; Raja
Reddy, K.; Skokotas, G.; Sato, F.; Xiao, X.-Y.; Hwang, C.-K.
J. Am. Chem. Soc. 1993, 115, 3558) in 70% yield from (R)-6
(5g, FLUKA). [ ]D -17.5 (c 1.6 CHCl3) (lit.+18 for (S)-isomer,
Hirama, M.; Uei, M. J. Am. Chem. Soc. 1982, 104, 4251). 1H
NMR CDCl3, 500MHz): 2.06-2.14 (m, 1H, CH-3), 2.22-
2.30 (m, 1H, CH-3), 2.40-2.50 (m, 1H, CH-2), 2.56-2.66 (m,
1H, CH-2), 3.56 (m, 1H, CH-OBn), 3.66 (m, 1H, CH-OBn),
4.55 (s, 2H, CH2Ph), 4.62-4.67 (m, 1H, CH-O), 7.22-7.40 (m,
5H, Ar).
(8) Methyl (R)-5-O-benzyl-4-O-tert-butyldimethylsilyl-4,5-
dihydroxypentanoate 11. Lactone 10 was transformed into the
crude methylester (Takeda, K.; Nakajima, A.; Yoshi, E.
Synlett 1997, 255) which was immediately treated with t-
butyldimethylsilyl chloride and imidazole in THF (r.t., 15 h)
to afford the silylether 11 (85% from 10). 1H NMR CDCl3,
500MHz): 0.0 (s, 6H, CH3Si), 0.88 (s, 9H, (CH3)3C), 1.74-
1.82 (m, 1H, CH-3), 1.90-1.98 (m, 1H, CH-3), 2.34-2.46 (m,
2H, CH2), 3.34 (m, 1H, CH-OBn), 3.40 (m, 1H, CH-OBn),
(11) (R)-1-O-Benzyl-5-oxo-1,2-decandiol 9. Title compound was
obtained by oxidation of 13 with PCC to ketone 14 and
deprotection of silyl ether with TBAF (Corey, E.J.;
Venkateswarlu, A. J. Am. Chem. Soc. 1972, 94, 6190) (70%
from 13, oil). [ ]D +3.3 (c 1 in CHCl3). 1H NMR CDCl3,
500MHz): 0.92 (t, 3H, CH3), 1.20-1.36 (m, 4H, CH2), 1.50-
1.60 (m, 2H, CH2), 1.60-1.70 (m, 1H, CH-3), 1.70-1.80 (m,
1H, CH-3), 2.36 (t, 2H, CH2CO), 2.48-2.62 (m, 2H, CH2CO),
3.32 (m, 1H, CH-OBn), 3.46 (m, 1H, CH-OBn), 3.74-3.80 (m,
1H, CH-O), 4.50 (s, 2H, CH2Ph), 7.22-7.40 (m, 5H, Ar). m/z
(APCI) 279 (MH+), 261.
(12) (R)-1-O-Benzyl-5-ethylendioxy-1,2-decandiol 15. The ketal
was prepared from ketone 14 with diethylene glycol under
boron trifluoride-ethyl etherate catalysis (Derguini, F.;
Linstrumelle, G. Tetrahedron Lett. 1984, 25, 5763 and Hase,
T.A.; Ourika, A.; Holmberg, C. J. Org. Chem. 1981, 46,
3137). The silylether was removed by reaction with TBAF (ref
11) affording 15 in 65% yield from 14. [ ]D+0.6 (c 2 in
CHCl3). 1H NMR CDCl3, 500MHz): 0.84 (t, 3H, CH3),
1.18-1.36 (m, 6H, CH2), 1.44-1.58 (m, 4H, CH2), 1.60-1.70
(m, 1H, CH), 1.74-1.84 (m, 1H, CH), 2.70 (br s, 1H,
exchang.), 3.33 (dd, 1H, J 1a,1b 9 Hz, J 1a,2 7.5 Hz, H-1a), 3.47
(dd, 1H, J 1b,2 3 Hz, H-1b), 3.78 (m, 1H, H-2), 3.86 (br s, 4H,
CH2-O), 4.54 (s, 2H, CH2Ph), 7.20-7.40 (m, 5H, Ar).
(13) The optical purity of (R)-9 was determined by 1H NMR
analysis of the MTPA-ester6 of (R)-15. (R,S)-15 was prepared
by PCC oxidation of (R)-15, followed by NaBH4 reduction in
methanol. In the spectrum of the racemic derivative two
signals centered at 4.42 and 4.52 ppm, due to the OCH2Ph
protons, were present, whereas in the spectrum of the (R)-15-
derivative the signal at 4.42 ppm was not detectable.
(14) (R)-1-O-Benzyl-5-ethylenedithio-1,2-decandiol 16. The
thioketal was prepared in one step procedure from ketone 14
by reaction in dichloromethane with 1,2-ethandithiol in the
presence of 0.2 equiv of boron trifluoride-diethyl ether (73%,
oil). [ ]D -1.4 (c 1 in CHCl3). 1H NMR (CDCl3, 500 MHz):
H
0.87 (t, 3H, CH3), 1.27 (m, 4H, CH2), 1.45 (m, 2H, CH2), 1.64
(m, 2H, CH2), 1.88 (m, 3H, CH2 and CH), 2.12 (m, 1H, CH),
2.32 (br s, 1H, exchang.), 3.24 (s, 4H, CH2-S), 3.33 (dd, 1H,
J
1a,1b 9.5 Hz, J 1a,2 9.5 Hz, H-1a), 3.51 (dd, 1H, J 1b,2 2.5 Hz,
H-1b), 3.80 (m, 1H, H-2), 4.54 (s, 2H, CH2Ph), 7.22-7.40 (m,
5H, Ar).
(15) (R)-1-O-Benzyl-2-O-(2,3,4,6-tetra-O-acetyl- -D-galacto-
pyranosyl)-5-ethylenedithio-1,2-decandiol 19. [ ]D -3 (c 1 in
Synlett 2001, No. 9, 1379–1382 ISSN 0936-5214 © Thieme Stuttgart · New York

1382
P. Ferraboschi et al.
LETTER
CHCl3). 1H NMR (CDCl3, 500 MHz): H 0.85 (t, 3H, CH3),
1.22-1.32 (m, 4H, CH2), 1.40 (m, 2H, CH2), 1.65-1.88 (m, 6H,
CH2), 1,94, 1,97, 2,05, 2,10 (4 s, 12H, 4 CH3CO), 3.22 (br s,
4H, CH2-S), 3.44 (dd, 1H, J 1a,1b 10.0 Hz, J 1a,2 6.0 Hz, H-1a),
3.62 (dd, 1H, J 1b,2 4.5Hz, H-1b), 3.72 (m, 1H, H-2), 3.82 (dd,
1H, JH’5,6a = JH’5,6b 6.5 Hz, H’-5), 4.02-4.10 (m, 2H, H’-6a,6b),
4.49 (s, 2H, CH2Ph), 4.55 (d, 1H, JH’1,2 8Hz, H’-1), 4.96 (dd,
1H, JH’2,3 10 Hz, JH’3,4 3 Hz, H’-3), 5.17 (dd, 1H, H’-2), 5.33
(br d, 1H, H’-4), 7.18-7.36 (m, 5H, Ar). m/z (CI/NH3) 702
[M+NH4]+.
Dowex 50 8 (H+ form) under reduced pressure (12 mm Hg)
at 50 °C for 10 min; after filtration, the solution was
lyophilized affording the desired 4b and 4c. (R)-2-O-( -D-
glucopyranosyl)-5-oxo-1,2-decandiol 4b. [ ]D -20 (c 0.5 in
H2O). 1H NMR (D2O, 500 MHz): H 0.70 (t, 3H, CH3), 1.02-
1.18 (m, 4H, CH2), 1.36 (m, 2H, CH2), 1.63 (m, 2H, CH2),
2.37 (m, 2H, CH2-6), 2.53 (m, 2H, CH2-4), 3.10 (dd, 1H, JH’1,2
8Hz, JH’2,3 9 Hz, H’-2), 3.16-3.34 (m, 3H, H’-3,4,5), 3.43 (dd,
1H, JH1a,1b 12.0 Hz, JH1a,2 6.0 Hz, H-1a), 3.56-3.46 (m, 2H, H-
1b and H’-6a), 3.63 (m, 1H, H-2), 3.72 (dd, 1H, JH’6a,6b 12 Hz,
JH’6b,5 1,5 Hz, H’-6b), 4.31 (d, 1H, H’-1). m/z (CI/NH3) 368
[M+NH4]+. (R)-2-O-( -D-galactopyranosyl)-5-oxo-1,2-
decandiol 4c. [ ]D -5 (c 0.5 in H2O). 1H NMR (D2O, 500
MHz): H 0. 70 (t, 3H, CH3), 1.02-1.18 (m, 4H, CH2), 1.38 (m,
2H, CH2), 1.63 (m, 2H, CH2), 2.37 (m, 2H, CH2-6), 2.53 (m,
2H, CH2-4), 3.30-3.61 (m, 7H, H-1a,1b and H’-2,3,5,6a,6b);
3.64 (m, 1H, H-2), 3.74 (br s, 1H, JH’3,4 3 Hz, H’-4), 4.25 (d,
1H, JH’1,2 8.0 Hz, H’-1). m/z (CI/NH3) 368 [M+NH4]+.
(18) Demopoulos, C.A.; Pinckard, R.N.; Hanahan, D.J. J. Biol.
Chem. 1979, 254, 9355.
(16) (R)-1-O-Benzyl-2-O-(2,3,4,6-tetra-O-acetyl- -D-gluco-
pyranosyl)-5-ethylenedithio-1,2-decandiol 20. [ ]D -6 (c 1 in
CHCl3). 1H NMR (CDCl3, 500 MHz): H 0.85 (t, 3H, CH3),
1.20-1.32 (m, 4H, CH2), 1.40 (m, 2H, CH2), 1.68-1.90 (m, 6H,
CH2), 1.96, 1.98, 2.02, 2.04 (4 s, 12H, 4 CH3CO), 3.18-3.26
(m, 4H, CH2-S), 3.44 (dd, 1H, JH1a,1b 10.0 Hz, JH1a,2 5.5 Hz, H-
1a), 3.57-3.64 (m, 2H, H-1b and H’-5), 3.72 (m, 1H, H-2),
4.03 (dd, 1H, JH’6a,6b 12.5 Hz, JH’5,6a 2.5 Hz, H’-6a), 4.16 (dd,
1H, JH’5,6b 4.5 Hz, H’-6b), 4.51 (s, 2H, CH2Ph), 4.59 (d, 1H,
JH’1,2 8Hz, H’-1), 4.96 (dd, 1H, JH’2,3 9.5 Hz, H’-2), 5.04 (dd,
1H, JH’3,4 = JH’4,5 = 10Hz, H’-4), 5.15 (dd, 1H, H’-3), 7.20-7.36
(m, 5H, Ar). m/z (CI/NH3) 702 [M+NH4]+.
(19) Andreesen, R.; Modolell, M.; Munder, P.G. Blood 1979, 54,
519.
(17) Compounds 19 and 20 were deprotected as follows. The
thioketal group was removed by adding dropwise at 0 °C a
solution of NBS in acetone to a solution of the substrate (0.25
g) in acetone (97% acetone+3% H2O) until disappareance of
the starting compound. After removal of the acetates with the
Zemplen reaction (MeONa/MeOH), the benzyl ether was
quantitatively hydrogenolyzed in MeOH with Pd/C as
catalyst. The mixture was filtered over Celite, evaporated to
dryness, and diluted with water. This solution was treated with
(20) (a). Nakamura, N.; Miyazaki, H.; Ohkawa, N.; Koike, H.;
Sada, T.; Asai, F.; Kobayashi, S. Chem. Pharm. Bull. 1984,
32, 2452. (b). Bonjouklian, R.; Phillips, M.L.; Kuhler, K.M.;
Grindey, G.B.; Poore, G.A.; Schultz, R.M.; Altom, M.G. J.
Med. Chem. 1986, 29, 2472.
Article Identifier:
1437-2096,E;2001,0,09,1379,1382,ftx,en;G10101ST.pdf
Synlett 2001, No. 9, 1379–1382 ISSN 0936-5214 © Thieme Stuttgart · New York