0.36 cm3, 0.36 mmol) for 2 h. Methanol (0.1 cm3) was added
dropwise, and the solution was warmed to 20 ЊC. Saturated aq.
Rochelles’s salt (1 cm3) was added, and the mixture was stirred
for 30 min before being filtered through Celite, dried (mag-
nesium sulfate), and concentrated in vacuo. The crude product
contained starting material, a mixture of the desired lactols,
and a third compound, assumed to be the compound arising
from over-reduction. The mixture of lactols was isolated by
column chromatography on silica gel [dichloromethane–diethyl
ether (5:1)], and immediately dissolved in anhydrous methanol
(5 cm3). A saturated solution of hydrogen chloride in anhydrous
methanol (1.0 cm3) was added, and the solution was stirred
for 48 h before being concentrated in vacuo. This gave the
same mixture of anomers of methyl 3-epi--daunosaminide
hydrochloride 43 as above (0.015 g, 31%).
Giorn. Microbiol., 1963, 11, 167; (c) M. Dubost, P. Ganter,
R. Maral, L. Ninet, S. Pinnert, J. Preud’homme and G.-H. Werner,
C. R. Hebd. Seances Acad. Sci., 1963, 257, 1813; (d) A. Di Marco,
M. Gaetani, L. Dorigotti, M. Soldati and O. Bellini, Tumori, 1963,
49, 203; (e) F. Arcamone, G. Franceschi, P. Orezzi, G. Cassinelli,
W. Barbieri and R. Mondelli, J. Am. Chem. Soc., 1964, 86, 5334;
( f ) F. Arcamone, G. Cassinelli, P. Orezzi, G. Franceschi and
R. Mondelli, J. Am. Chem. Soc., 1964, 86, 5335; (g) F. Arcamone,
G. Cassinelli, G. Franceschi, R. Mondelli, P. Orezzi and S. Penco,
Gazz. Chim. Ital., 1970, 100, 949.
3 (a) F. Arcamone, G. Franceschi, S. Penco and A. Selva, Tetrahedron
Lett., 1969, 1007; (b) International Symposium on Adriamycin, ed.
S. K. Carter, A. Di Marco, M. Ghione, I. H. Krakoff and G. Mathé,
Springer-Verlag, Berlin and New York, 1972.
4 (a) F. M. Hauser and S. R. Ellenberger, Chem. Rev., 1986, 86, 35;
(b) I. F. Pelyvás, C. Monneret and P. Herczegh, Synthetic Aspects
of Aminodeoxy Sugars of Antibiotics, Springer-Verlag, Berlin,
1988.
5 (a) G. Grethe, T. Mitt, T. H. Williams and M. R. Uskokovic, J. Org.
Chem., 1983, 48, 5309; (b) D. Picq, G. Carret, D. Anker and
M. Abou-Assali, Tetrahedron Lett., 1985, 26, 1863; (c) Y. Kimura,
T. Matsumoto, M. Suzuki and S. Terashima, Bull. Chem. Soc. Jpn.,
1986, 59, 663; (d) M. K. Gurjar and S. M. Pawar, Tetrahedron Lett.,
1987, 28, 1327; (e) Y. St-Denis, J.-F. Lavallée, D. Nguyen and
G. Attardo, Synlett, 1995, 272; ( f ) B. Abbaci, J.-C. Florent and
C. Monneret, Bull. Soc. Chim. Fr., 1989, 667; (g) L. Daley, P. Roger
and C. Monneret, J. Carbohydr. Chem., 1997, 16, 25; (h) P. Herczegh,
M. Zsély, I. Kovács, G. Batta and F. J. Sztaricskai, Tetrahedron
Lett., 1990, 31, 1195; (i) I. Kovács, P. Herczegh and F. J. Sztaricskai,
Tetrahedron, 1991, 47, 7837; (j) D. Socha, M. Jurczak and M.
Chmielewski, Tetrahedron, 1997, 53, 739.
6 (a) A. Warm and P. Vogel, J. Org. Chem., 1986, 51, 5348; (b) L.-X.
Dai, B.-L. Lou and Y.-Z. Zhang, J. Am. Chem. Soc., 1988, 110, 5195;
(c) S. Nagumo, I. Umezawa, J. Akiyama and H. Akita, Chem.
Pharm. Bull., 1995, 43, 171; (d) F. M. Hauser, R. P. Rhee and S. R.
Ellenberger, J. Org. Chem., 1984, 49, 2236; (e) M. Ono, C. Saotome
and H. Akita, Heterocycles, 1997, 45, 1257.
7 (a) D.-C. Ha and D. J. Hart, Tetrahedron Lett., 1987, 28, 4489; (b)
M. Hatanaka and I. Ueda, Chem. Lett., 1991, 61; (c) M. Hirama,
I. Nishizaki, T. Shigemoto and S. Itô, J. Chem. Soc., Chem.
Commun., 1986, 393; (d) Y. Hamada, A. Kawai and T. Shiori,
Tetrahedron Lett., 1984, 25, 5409; (e) S. Hanessian and J. Kloss,
Tetrahedron Lett., 1985, 26, 1261; ( f ) H. Iida, N. Yamazaki and
C. Kibayashi, J. Org. Chem., 1986, 51, 4245; (g) T. Hiyama,
K. Kobayashi and K. Nishide, Bull. Chem. Soc. Jpn., 1987, 60, 2127;
(h) Y. Kita, F. Itoh, O. Tamura, Y. Y. Ke and Y. Tamura, Tetrahedron
Lett., 1987, 28, 1431; (i) Y. Kita, F. Itoh, O. Tamura, Y. Y. Ke,
T. Miki and Y. Tamura, Chem. Pharm. Bull., 1989, 37, 1446; (j)
A. Dondoni, G. Fantin, M. Fogagnolo and P. Merino, Tetrahedron,
1990, 46, 6167; (k) J. Jurczak, J. Kozak and A. Golebiowski,
Tetrahedron, 1992, 48, 4231.
Preparation of methyl ꢀ-L-daunosaminide hydrochloride 44
(3S,4S,5S)-3-[N-(tert-Butoxycarbonyl)amino]-5-hydroxy-
hexano-4-lactone 39 (0.150 g, 0.612 mmol) was reduced with
DIBAL in dichloromethane under the same conditions as for
the (3S,4R,5R)-diastereomer 38 above. The residue was purified
by column chromatography on silica gel, eluting with diethyl
ether, to give a mixture of lactols, which was not characterised,
but was immediately treated with methanolic hydrogen chloride
(vide infra).
Elution of the column with a more polar solvent mixture
(diethyl ether–methanol 20:1) gave the over-reduction product
(3S,4S,5S)-3-[N-(tert-butoxycarbonyl)amino]hexane-1,4,5-
triol 41 as an off-white solid (0.030 g, 20%), mp 98–100 ЊC
(Found: C, 53.11; H, 9.21; N, 5.92. C11H23NO5 requires C,
53.00; H, 9.30; N, 5.62%); [α]D21 Ϫ4.6 (c 1.15 in CHCl3); νmax
-
(CHCl3 solution)/cmϪ1 3620 (m, OH), 3439 (m, NH), 1686 (s,
carbamate C᎐O), 1520 (s, carbamate NH); m/z (CI, NH ) 250
᎐
3
(MHϩ, 10%), 194 (50, MHϩ Ϫ C4H8), 150 (60, MHϩ Ϫ C4H8 Ϫ
CO2); δH(250 MHz; C5D5CD3; 70 ЊC) 1.10 [3H, d, J 6.4,
C(6)H3], 1.37 [9H, s, OCMe3], 1.63–1.77 [2H, m, C(2)H2], 3.00
[1H, dd, J 6.7 and 3.0, C(4)H], 3.43–3.57 and 3.64–3.78 [2H
and 2H, m, C(1)H2, C(3)H and C(5)H], 5.09 [1H, br d, J 7.3,
NH]; δC(50.3 MHz; CDCl3) 19.1 [C(6)], 28.2 [OCMe3], 32.8
[C(2)], 49.8 [C(3)], 58.7 [C(1)], 66.9 [C(5)], 76.9 [C(4)], 80.3
[OCMe3], 157.7 [NCO].
The mixture of lactols was treated with methanolic hydrogen
chloride as before. Column chromatography of the residue
on silica gel (methanol–ethyl acetate 3:7) gave methyl α--
daunosaminide hydrochloride 44 as a white solid (0.044 g, 36%
from the lactone), mp 179–181 ЊC (decomp.) [lit.,2g mp 188–
190 ЊC (decomp.)]; [α]D23 Ϫ123 (c 0.97 in MeOH) {lit.,2g [α]D
Ϫ140 (c 1 in MeOH)}. Further purification was achieved by
recrystallisation from methanol–diethyl ether to give material
(11 mg), mp 184 ЊC (decomp.); [α]D23 Ϫ146 (c 0.64 in MeOH);
δH(500 MHz; d5-pyridine) 1.37 [3H, d, J 6.5, C(6)H3], 2.38 [1H,
dd, J2A,2B 12.5, J2B,3 4.6, C(2)HB], 2.47 [1H, app td, J 12.5 and
3.5, C(2)HA], 3.26 [3H, s, OMe], 3.92 [1H, q, J5,6 6.5, C(5)H],
4.22 [1H, ddd, J2A,3 12.5, J2B,3 4.6, J3,4 2.9, C(3)H], 4.47 [1H, d,
J3,4 2.9, C(4)H], 4.85 [1H, d, J1,2A 3.5, C(1)H], 5.0 [4H, br s, NH
8 P. A. Wade, S. G. D’Ambrosio, J. A. Rao, S. Shah-Patel, D. T. Cole,
J. K. Murray, Jr. and P. J. Carroll, J. Org. Chem., 1997, 62, 3671.
9 P. G. Sammes and D. Thetford, J. Chem. Soc., Perkin Trans. 1, 1988,
111.
10 (a) P. M. Wovkulich and M. R. Uskokovic, Tetrahedron, 1985, 41,
3455; (b) S.-Y. Po and B.-J. Uang, Tetrahedron: Asymmetry, 1994, 5,
1869.
11 (a) S. G. Davies and O. Ichihara, Tetrahedron: Asymmetry, 1991, 2,
183; (b) S. G. Davies and I. A. S. Walters, J. Chem. Soc., Perkin
Trans. 1, 1994, 1129; S. G. Davies, O. Ichihara and I. A. S. Walters,
(c) J. Chem. Soc., Perkin Trans. 1, 1994, 1141; (d) Synlett, 1993, 461;
(e) S. G. Davies, O. Ichihara, I. Lenoir and I. A. S. Walters, J. Chem.
Soc., Perkin Trans. 1, 1994, 1411.
12 S. G. Davies and D. R. Fenwick, J. Chem. Soc., Chem. Commun.,
1995, 1109.
1
and OH]. This material was identical by mixed H NMR with
authentic methyl α--daunosaminide hydrochloride, prepared
from methyl β--daunosaminide hydrochloride (purchased
from Sigma Chemical Company) by treatment with methanolic
hydrogen chloride, followed by two recrystallisations from
methanol–diethyl ether.
13 M. E. Bunnage, S. G. Davies and C. J. Goodwin, (a) J. Chem. Soc.,
Perkin Trans. 1, 1993, 1375; 1994, 2385; (b) Synlett, 1993, 731; (c)
M. E. Bunnage, S. G. Davies, C. J. Goodwin and O. Ichihara,
Tetrahedron, 1994, 50, 3975; (d) M. E. Bunnage, A. J. Burke, S. G.
Davies and C. J. Goodwin, Tetrahedron: Asymmetry, 1994, 5, 203;
1995, 6, 165; (e) S. G. Davies, C. J. R. Hedgecock and J. M.
McKenna, Tetrahedron: Asymmetry, 1995, 6, 2507; ( f ) S. G. Davies
and D. R. Fenwick, Chem. Commun., 1997, 565; (g) D. J. Dixon and
S. G. Davies, Chem. Commun., 1996, 1797; (h) S. G. Davies and
O. Ichihara, Tetrahedron: Asymmetry, 1996, 7, 1919; (i) S. G. Davies
and G. Bhalay, Tetrahedron: Asymmetry, 1996, 7, 1595; (j) A. J.
Burke, S. G. Davies and C. J. R. Hedgecock, Synlett, 1996, 621; (k)
Q. Li, D. T. W. Chu, K. Raye, A. Claiborne, L. Seif, B. Macri and
J. J. Plattner, Tetrahedron Lett., 1995, 36, 8391.
References
1 (a) J. W. Lown, Chem. Soc. Rev., 1993, 22, 153; (b) Bioactive
Molecules Volume 6. Anthracycline and Anthracenedione-Based
Anticancer Agents, ed. J. W. Lown, Elsevier, Amsterdam, 1988; (c)
F. Arcamone, Doxorubicin Anticancer Antibiotics, Academic Press,
New York, 1981.
2 (a) A. Grein, C. Spalla, A. Di Marco and G. Canevazzi,
Giorn. Microbiol., 1963, 11, 109; (b) G. Cassinelli and P. Orezzi,
14 S. G. Davies and G. D. Smyth, Tetrahedron: Asymmetry, 1996, 7,
1273.
J. Chem. Soc., Perkin Trans. 1, 1999, 3089–3104
3103