Ketone 8 (5 g, 12.4 mmol) and HCOOMe (3.1 mL, 49.8 mmol) in dry benzene (60 mL) were reacted in presence of
NaH (57–63% in oil, 2.1 g, 49.8 mmol), in a similar way as described for the synthesis of 14a and 14b, to give a mixture
1
of 17a and 17b as an amorphous solid in a 10:1 ratio, according to H NMR data. This material was purified by flash
column chromatography [silica gel, n-hexane with gradient AcOEt (5–35%)] and used for the next reaction as a mixture of
isomers (summary yield of 17a and 17b was 5.0 g, 93%). Individual isomers 17a (0.091 g, 19%) and 17b (0.06 g, 12%)
were obtained by flash column chromatography the sample of the reaction mixture (0.49 g, ratio 17a:17b = 2:1) [silica gel,
32
[
α
]D
n-hexane with gradient AcOEt (5-30%)] and re-crystallised from CH
(
3
OH. M.p. (compound 17a) 141.4–145.7ºC.
1
+120º
c 0.10, CHCl
=4.4, OH), 8.29 (dd, 1H, J26, OH=4.4, J26, 1'=0.7, H-26), 3.63 (s, 3H, CH
3
).HRMS: m/z calcd for C26
H
38
O
5
: 430.2714; found: 430.2712. H NMR (CDCl
-25), 2.49 (dd, 1H, J11a, 9 =12.9, J=12.4, H-11a),
3
): δ = 14.21 (d, 1H, JOH,
2
2
6
3
2
.45-2.28 (m: 2H, 2.40 (dd, 1H, J=20.3, J4a, 5=10.5, H-4a); 2.35 (ddd, 1H, J=15.8, J23, 22=9.8, J23, 22′=5.3, H-23)), 2.28-
2
2
2
(
[
2 2
.15 (m: 2H, 2.23 (ddd, 1H, J=15.8, J23′, 22′=9.2, J23′, 22=6.8, H-23'); 2.19 (d, 1H, J=15.3, H-1)), 2.08-1.75 (m: 8H, 2.04
2
2
dd, 1H, J=15.3, J1', 26=0.7, H-1'); [1.97]–H-17; 1.92 (dd, 1H, J=12.4, J11e, 9=4.9, H-11e); [1.89]–H-16; [1.88]–H-6;
2
1.83]–H-5; [1.83]–H-8; [1.79]–H-22), 1.70 (m, 1H, H-15), 1.57 (m, 1H, H-7e), 1.45-1.20 (m: 8H, 1.41 (dd, 1H, J=20.3,
J
4e, 5=7.8, H-4e); 1.40 (ddd, 1H, J9, 11a=12.9, J9, 8=11.2, J9, 11e=4.9, H-9); [1.37]–H-22'; [1.34]–H-6'; [1.32]–H-16'; [1.31]–H-
4; [1.30]–H-15'; [1.26]–H-20), 1.12 (s, 3H, CH -19), [1.10]–H-7a, 1.00 (s, 3H, CH -18), 0.82 (d, 3H, J21, 20=6.6, H-21).
): δ = 213.55 (s, C-12), 187.76 (s, C-3), 182.32 (d, C-26), 174.47 (s, C-24), 106.33 (s, C-2), 57.98 (d, C-
1
3
3
1
3
C NMR (CDCl
3
1
3
6 28
4), 57.36 (s, C-13), 51.31 (q, C-25), 46.37 (d, C-17), 43.84 (d, C-9), 38.01 (t, C-11), 37.92 (d, C-5), 35.47 (d, C-20),
5.35 (s, C-10), 35.01 (d, C-8), 34.92 (t, C-1), 33.45 (t, C-4), 31.16 (t, C-23), 30.39 (t, C-22), 27.34 (t, C-16), 25.20 (t, C-
), 24.98 (t, C-7), 24.09 (t, C-15), 21.72 (q, C-19), 18.45 (q, C-21), 11.59 (q, C-18). Compound 17b: M.p. 171.6-176.7ºC.
1
+106º (c 0.10, CHCl ). HRMS: m/z calcd for C H O : 430.2714; found: 430.2712. H NMR (CDCl ): δ = 15.45 (d,
3
26 38
5
3
2
-25), 2.55 (dd, 1H, J11a, 9=12.9, J=12.4, H-11a),
1
2
H, JOH, 26 = 4.0, OH), 8.68 (d, 1H, J26, OH = 4.0, H-26), 3.62 (s, 3H, CH
3
2
.49 (ddd, 1H, J5,6a~J5,6e~2.9, J5,2a=1.5, H-5), 2.41-2.28 (m: 2H, 2.34 (dddd, 1H, J=19.9, J2a, 1a=12.7, J2a, 1e=6.1, J2a, 5=1.5,
2
2
H-2a); 2.33 (ddd, 1H, J=15.8, J23, 22=9.8, J23, 22′=5.3, H-23)), 2.28-2.15 (m: 2H, 2.24 (ddd, 1H, J=19.9, J2e, 1a=6.2, J2e,
2
1
2
e
=2.1, H-2e); 2.22 (ddd, 2H, J=15.8, J23′, 22′=9.2, J23′, 22=6.8, H-23′)), 2.06-1.93 (m: 2H, [1.97] –H-17; 1.96 (dd, 1H,
J=12.4, J11e, 9=4.6, H-11e)), 1.93-1.84 (m: 3H, [1.90]–2H-H-6; [1.89]–H-16), 1.84-1.73 (m: 2H, [1.80] –H-8; [1.78]–H-
2
2), 1.73-1.55 (m: 2H, [1.66] –H-15; 1.62 (ddd, 1H, J=14.1, J1a, 2a=12.7, J1a, 2e=6.2, H-1a)), 1.55-1.18 (m: 8H, 1.48 (ddd,
2
1
2
2
H, J9, 11a=12.9, J9, 8=11.2, J9, 11e=4.6, H-9); [1.48] –H-7e; 1.41 (ddd, 1H, J=14.1, J1e, 2a=6.1, J1e, 2e=2.1, H-1e), [1.34]–H-
2’; [1.29] –H-15’; [1.28]–H-16’; [1.27] –H-14; [1.25]–H-20), 1.09 (s, 3H, CH
3
-19), 1.00 (s, 3H, CH
): δ = 213.63 (s, C-12), 188.24 (s, C-3), 185.41 (d, C-26),
74.42 (s, C-24), 109.09 (s, C-4), 58.04 (d, C-14), 57.33 (s, C-13), 51.28 (q, C-25), 46.33 (d, C-17), 44.33 (d, C-9), 40.74
d, C-5), 38.19 (t, C-11), 35.44 (d, C-20), 35.25 (d, C-8), 34.86 (s, C-10), 32.22 (t, C-1), 31.13 (t, C-23), 30.36 (t, C-22),
3
-18), 0.91 (m, 1H,
1
3
3 3
H-7a), 0.81 (d, 3H, J21, 20 = 6.6, CH -21). C NMR (CDCl
1
(
2
1
7.90 (t, C-2), 27.29 (t, C-16), 25.48 (t, C-7), 24.08 (t, C-15), 23.70 (t, C-6), 21.90 (q, C-19), 18.43 (q, C-21), 11.54 (q, C-
8).
4
.1.19. Reaction of 2- and 4-hydrohymethylene derivatives (17a and 17b) with hydroxylamine
A mixture of 17a and 17b (860 mg, 2.0 mmol, a:b=1.6:1) in MeOH (30mL) and H
NH OH*HCl (155 mg, 2.2 mmol) for 3 h at 40ºC (the reaction course was monitored by TLC). The reaction mixture was
concentrated under reduced pressure (v~5 mL) and then diluted with CH Cl /Et O (40 mL, 1:3, v/v) and washed with
saturated aqueous NaHCO and brine. The organic phase was dried over anhydrous MgSO and evaporated to dryness to
give a mixture of 18a and 18b (0.81 g, 95%) as a yellow solid. According to H NMR data, the reaction mixture contained
8a:18b in the ratio 1.5:1. This material was used for the next reaction as a mixture of isomers without further
purification. Individual isomers 18a (0.124 g, 25%) and 18b (0.102 g, 21%) were obtained by flash column
chromatography the sample of the reaction mixture (0.49 g) [silica gel, benzene with gradient CH Cl (0–100%)] and re-
+66º (c 0.10, CHCl ).HRMS: m/z calcd
):2 δ = 7.98 (s, 1H, H-26), 3.63 (s, 3H, CH -25), 2.75 (ddd,
H, J = 18.2, J4a, 5 = 10.7, J4a,1a = 2.5, H-4a), 2.61 (ddd, 1H, J = 18.2, J4e, 5 = 6.7, J4e,1a = 1.5, H-4e), 2.49 (d, 1H, J =
2
O (1 mL) was reacted with
2
2
2
2
3
4
1
1
2
2
28
crystallisation from CH
3
OH. M.p. (compound 18a) 167.2ºC (decomposition).
3
1
for C26
H
37NO
4
: 427.2717; found: 427.2718. H NMR (CDCl
3
3
2
2
1
1
2
2
6.3, H-1e), 2.48 (dd, 1H, J = 12.2, J11a,9a = 13.7, H-11a), 2.34 (ddd, 1H, J = 15.8, J23, 22 = 9.8, J23, 22′ = 5.3, H-23), 2.21
2
2
(
ddd, 1H, J = 15.8, J23′, 22′ = 9.2, J23′, 22= 6.8, H-23′), 2.11 (ddd, 1H, J = 16.3, J1a,4a = 2.5, J1a,4e = 1.5, H-1a), 2.06-1.83 (m:
2
2
6
[
H, 2.01 (dddd, 1H, J = J6a,7a = 13.7, J6a, 7e = J6a, 5 = 4.5, H-6a); [1.99] –H-5; 1.96 (dd, 1H, J = 12.2, J11e,9a = 4.4, H-11e);
2
1.94] –H-17; [1.90] –H-16; [1.89] –H-8), 1.78 (dddd, 1H, J = 13.3, J22,23 = 9.8, J22,23’ = 6.8, J22, 20= 3.0, H-22), 1.73-1.54
(
m: 2H, [1.69] –H-15; [1.62] –H-7), 1.49 (m, 1H, H-6e), 1.40-1.10 (m: 7H, [1.34] –H-22′; [1.34] –H-9; [1.30] –H-16′;
[
1.30] –H-15′; [1.27] –H-14; [1.24] –H-20; [1.19] –H-7′), 1.18 (s, 3H, CH
.6, H-21). C NMR (CDCl
3
3
-19), 1.00 (s, 3H, CH
): δ = 213.37 (s, C-12),174.48 (s, C-24), 166.09 (s, C-3), 149.13 (d, C-26), 109.40 (s, C-2),
7.94 (d, C-14), 57.34 (s, C-13), 51.32 (q, C-25), 46.33 (d, C-17), 43.66 (d, C-9), 39.36 (d, C-5), 38.53 (t, C-11), 36.62 (s,
3
-18), 0.80 (d, 3H, J21, 22 =
1
3
6
5
C-10), 35.48 (d, C-20), 35.04 (d, C-8), 31.17 (t, C-23), 30.37 (t, C-1), 30.37 (t, C-22), 27.35 (t, C-16), 25.51 (t, C-6), 25.16
(t, C-7), 24.04 (t, C-15), 23.36 (t, C-4), 22.21 (q, C-19), 18.44 (q, C-21), 11.65 (q, C-18). Compound 18b: M.p. 213.1-
2
8
1
: 427.2717; found: 427.2714. H NMR (CDCl
α
2
7
[
15.6ºC.
.99 (s, 1H, H-26), 3.62 (s, 3H, CH
+119º (c 0.12, CHCl
3
). HRMS: m/z calcd for C26
H37NO
4
3
): δ =
2
3
-25), 2.72-2.50 (m: 4H, [2.68]-H-2, 2.60 (dd, 1H, J11a, 9=13.3, J=12.3, H-11a(β)),
2
2
2.56]-H-5, [2.54]-H-2), 2.34 (ddd, 1H, J=15.8, J23, 22=9.8, J23, 22′=5.3, H-23), 2.21 (ddd, 1H, J=15.8, J23′, 22′=9.2, J23′,
2
2
2
2
=6.8, H-23’), 2.04-1.66 (m: 8H, 2.01 (dddd, J=J6a, 7a=14.0, J6a, 7e= J6a, 5=4.3, H-6a(β)), 2.00 (dd, 1H, J=12.3, J11e,
2
9
=4.7, H-11e(α)), [1.93]-H-17, [1.84]-H-1, 1.84 (dddd, J=14.0, J6e, 7a=J6e, 7e=J6e, 5=3.2, H-6e(α)), [1.85]-H-16, [1.78]-H-
2, 1.74 (dddd, 1H, J8, 7a=11.7, J8, 9=J8, 14=11.0, J8, 7e=3.4, H-8)), 1.63 (m, 1H, H-15), 1.56-1.46 (m: 2H, [1.58]-H-1, 1.51
2
(
2
dddd, 1H, J=13.5, J7e, 8=3.4, J7e, 6a~J7e, 6e~3, H-7e(β))), 1.39-1.11 (m: 9H, 1.35 (ddd, 1H, J9, 11a=13.3, J9, 8=11.0, J9,
1e=4.7, H-9), [1.27]-H-15, [1.27]-H-16, [1.23]-H-20, [1.22]-H-22, [1.16]-H-14, 1.15 (s, 3H, CH -19)), 1.00 (s, 3H, CH
): δ = 213.69 (s, C-12),174.46 (s, C-24), 166.94 (s, C-3), 148.26 (d,
1
3
3
-
1
3
1
8), 0.80 (d, 3H, J21, 22 = 6.6, H-21). C NMR (CDCl
3
C-26), 114.54 (s, C-4), 57.90 (d, C-14), 57.24 (s, C-13), 51.31 (q, C-25), 46.28 (d, C-17), 44.08 (d, C-9), 38.72 (d, C-5),
14