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A. Horvath et al. / Tetrahedron 56 (2000) 7469–7476
1
(COOMe), 169.0 (C-1), 165.6 (C-8), 136.2, 132.5,
131.7,130.6 (C-19, C-23, C-24, C-28), 129.6, 128,6 (C-20,
C-29), 96.9 (C-10), 84.2 (C-32), 79.4 (C-22), 75,3, 75.2
(C-15, C-13,), 75.0 (C-26), 74.0 (C-14), 73.5 (C-33),
58.12, 57.0 (3OCH3), 52.0 (C-2), 50.8 (COOCH3), 42.2
(CH2COO), 25.8 (SiC(CH3)3), Ϫ4.5, Ϫ4.7 (Si(CH3)2).
Compound 13a. H NMR (CDCl3): two conformers (1:1),
due to complicated overlapping, signals of both com-
formers: d 4.25 and 4.24 (d, J10.5 Hz, H-23), 3.98 (s,
OH), 3.79 and 3.78 (dd, J11 Hz, J29.5 Hz, H-14), 3.64
and 3.62 (s, COOCH3), 2.94 (m, H-21), 2.43 (m, H-24), 2.55
(dd, J13.5 Hz, J213.6 Hz, CH2COO) and 2.17 (dd,
J110 Hz, J213.6 Hz, CH2COO). 13C NMR (CDCl3): d
195.9 (C-9), 172.9, 172.6 (COOCH3), 170.1, 169.5 (C-1),
164.2, 163.5 (C-8), 154.2, 153.8 (C-22), 133.7, 132.9
(C-19), 131.6 (C-28), 130.2, 129.6 (C-29), 127.2, 126.8
(C-20), 109.4, 108.6 (C-23), 99.4, 98.2 (C-10), 84.4, 84.2
(C-32), 77.7 (C-15), 75.5, 75.4, 75.3 (C-13, C-33), 73.6
(C-14), 72.9, 72.0 (C-26), 57.9, 57.7, 56.9, 56.7, 56.4,
56.2,(3OCH3), 56.3, 53.5 (C-2), 51.5, 51.3 (COOCH3),
49.6, 49.4 (C-18). FABMS: Calcd (MϩLi)ϩ Calcd for
C58H101NO13SiLi m/e 1082, found 1082.
1
Compound 12. H NMR (CDCl3): d 5.64 (d, J16 Hz,
H-23), 5.52 (d, J1.5 Hz, 10-OH), 5.08 (s, H-26), 5.00
(m, H-29 and H-2), 4.98 (dd, J18.9 Hz, J216 Hz,
H-24), 4.57 (d, J10.7 Hz, H-20), 4.43 (br, d, J10.4 Hz,
He-6), 3.70 (COOMe), 2.76 and 2.70 (Ja,b16.4 Hz,
COCH2), 0.08–0.065 (4s, Si(CH3)2). 13C NMR (CDCl3): d
197.0 (C-9), 172.0 (COOMe), 169.2 (C-1), 166.0 (C-8),
136.2,134.4, 130.7, 130.2 (C-19, C-23, C-24, C-28),
129.5, 128.7 (C-20, C-29), 96.9 (C-10), 84.2 (C-32), 79.0
(C-22), 75.0 (C-26), 73.5 (C-33), 55.8 (C-2), 51.5
(COOCH3), 42.4 (CH2COO), 26.0 (SiC(CH3)3), Ϫ1.6,-2.6,
Ϫ4.5, Ϫ4.7 (Si(CH3)2). FABMS: Calcd (MϩLi)ϩ Calcd for
C58H101NO13Si2Li m/e 1082, found 1082.
1
Compound 13b. H NMR (CDCl3): d 5.21 (d, J8 Hz,
H-29), 5.20 (d, J4.9 Hz, H-2), 5.06 (d, J8 Hz, H-20),
4.98 (d, J8.7 Hz, H-26), 4.51 (d, J7.4 Hz, H-23), 3.79
(dd, J12.7 Hz, J29.6 Hz, H-14), 3.63 (s, COOCH3), 3.17
(dt, J13.3 Hz, J213 Hz, Ha-6), 2.86 (m, H-24), 2.74 (m,
H-21), 2.59 (dd, J14.1 Hz, J215.7 Hz, CH2COO), 2.25
(dd, J111.2 Hz, J215.7 Hz, CH2COO), 2.03 (ddd,
J12.4 Hz, J28.7 Hz, J37 Hz, H-25), 0.89 (SiC(CH3)3).
13C NMR (CDCl3): d 195.6 (C-9), 173.0 (COOCH3), 169.0
(C-1), 166.5 (C-8), 155.4 (C-22), 136.6 (C-19), 134.2
(C-29), 131.9 (C-28), 127.8 (C-20), 104.2 (C-23), 98.2
(C-10), 84.2 (C-32), 82.7 (C-15), 77.5, (C-26), 75.0
(C-33), 74.0 (C-13, C-14), 57.8, 57.3, 56.0 (3OCH3), 51.8
(COOCH3), 51.2 (C-2). FABMS: Calcd (MϩLi)ϩ Calcd for
C58H101NO13SiLi m/e 1082, found 1082.
D
23,24-22-Dihydro-22-(methoxycarbonyl)methyl-asco-
mycin (11). According to the procedure as described for 7, a
mixture of 10 (55 mg, 0.06 mmol) and 0.5 ml of 1 N HCl in
acetonitrile (1 ml) was stirred for 1 h, and then worked up.
The residue was purified by chromatography (hexane/ethyl
acetate 1:5) to give 39 mg (82%) 11 as colourless foam. 1H
NMR (CDCl3): d 5.56 (d, J16.1 Hz, H-23), 5.29 (dd,
J18.5 Hz, J216.1 Hz, H-24), 5.12 (br, d, J8.2 Hz,
H-26), 5.06 (d, J9.1 Hz, H-29), 4.91 (d, J1 Hz,
10-OH), 4.76 (d, J4.8 Hz, H-2), 4.69 (d, J10.4 Hz, H-
20), 4.43 (br, d, J10.5 Hz, He-6), 4.17 (s, OH), 3.75 (s,
COOCH3), 3.61 (dd, J12.1 Hz, J29.6 Hz, H-15), 3.56 (d,
J9.6 Hz, H-14), 2.65 (d, J1.3 Hz, COCH2), 1.66 (s,
18CH3), 1.51 (s, 19CH3), 1.04 (d, J6.3 Hz, 11CH3), 1.01
(d, J6.5 Hz, 17CH3), 0.92 (d, J7 Hz, 25CH3), 0.76 (t,
J7.5 Hz, H-40). 13C NMR (CDCl3): d 196.6 (C-9), 173.9
(COOCH3), 169.0 (C-1), 165.5 (C-8), 136.3 (C19), 132.6
(C-23), 131.6 (C-24), 131.0 (C-28), 129.6 (C-29), 128.6
(C20), 97.0 (C-10), 84.2 (C-32), 79,5 (C-26), 75.5 (C-22),
75.0 (C-15), 74.0 (C-33), 73.8 (C-13), 73.6 (C-14), 57.0,
56.6 (2OCH3), 56.1 (C-2 and OCH3), 52.0 (COOCH3),
50.7 (C-18), 49.1 (C-21), 42.3 (CH2COO), 39.0 (C-6),
38.2 (C-25), 34.9 (C-30, C-31), 34.7 (C-16), 34.5 (C-11),
32.3 (C-12), 31.2 (C-34), 30.6 (C-35), 28.1 (C-12), 27.8
(C-3), 24.4 (C-5), 22.2 (C-39), 21.4 (C-4), 21.1 (17CH3),
16.5, 16.4 (11CH3, 15CH3, 19CH3), 14.8 (28CH3), 13.8
(25CH3), 12.2 (C-40). FABMS: Calcd (MϩLi)ϩ Calcd for
C46H73NO13Li m/e 854, found 854.
24-Deoxy-24-(methoxycarbonyl)methyl-ascomycin (14).
A solution of 13a (110 mg, 0.1 mmol) in acetonitrile
(2 ml) was treated with 40% aqueous HF solution (20 ml)
at rt for 45 min. The mixture was neutralised with saturated
aqueous NaHCO3 solution and extracted with ethyl acetate
(3×5 ml). The combined organic layers were washed with
water and brine, dried over MgSO4 and evaporated in vacuo.
The crude product was purified by chromatography (hexane/
ethyl acetate 1:2) yielded 53 mg (63%) 14 as a colourless
foam.
According to the procedure above, a solution of 13b
(125 mg, 0.12 mmol) in acetonitrile (2 ml) was treated
with 40% aqueous HF (20 ml) for 45 min and then worked
up. Purification by chromatography afforded 14 61 mg
1
(62%). H NMR (CDCl3): two conformers (5:4), signals
of the major conformer: d 5.17 (s, H-26), 4.98 (m, H-20,
H-29), 4.45 (t, J3.7 Hz, H-2), 4.40 (d, br, J10.7 Hz, Heq-
6), 3.82 (dd, J12.4 Hz, J29.5 Hz, H-14), 3.67 (COOCH3),
3.01 (ddd, J14.5 Hz, J29 Hz, J311.5 Hz, H-32). 13C
NMR (CDCl3): d 212.3 (C-22), 196.4 (C-9), 173.1
(COOCH3), 169.4 (C-1), 165.6 (C-8), 138.7 (C-19), 131.6
(C-28), 128.7 (C-29), 123.7 (C-20), 98.0 (C-10), 84.2
(C-32), 79.8 (C-26), 75.9, 74.1 (C-13, C-15), 73.5 (C-33),
73.4 (C-14), 56.3 (C-2) 55.6 (C-21), 51.5 (COOCH3), 48.5
(C-18), 40.0 (CH2COO), 40.0 (C-6), 36.5 (C-25), 34.9
(C-31), 33.3 (C-16), 32.5 (C-12), 31.2 (C-34), 30.6
(C-35), 27.7 (C-17), 26.3 (C-3), 25.1 (C-39), 24.3 (C-5),
21.2 (C-4). FABMS: Calcd (MϩLi)ϩ Calcd for
C46H73NO13Li m/e 854, found 854.
Reaction with lithium perchlorate
A mixture of 9 (444 mg, 0.5 mmol) and 1-tert-butyl-
dimethylsilyloxy-1-methoxy-ethene (242 mg, 1.3 mmol) in
anhydrous CH2Cl2 (5 ml) was treated with lithium
perchlorate (1.7 mg 0.016 mmol). After stirring at rt for
30 min, the mixture was diluted with saturated aqueous
NaHCO3 solution and ethylacetate. The organic layer was
washed with water and brine, dried over MgSO4 and con-
certrated in vacuo. Upon chromatography of the residue
(hexane/ethyl acetate 6:1!4:1) 90 mg 13a (16.6%) and
154 mg 13b (29%) were obtained along 89 mg 12 (16%).