Methanol → Spongistatin 3

HRID 1728779Notes

Reaction equation

[CH3:1][C@@H:2]1[C@@H:51]([OH:52])[CH2:50][C@@:48]2([OH:53])[O:49][C@@H:3]1[CH2:4][CH2:5][CH2:6][CH:7]=[CH:8][C@@H:9]1C[C@@]3([O:19][C@H:18]([CH2:20][C:21]([C@@H:23]([CH3:83])[C@@H:24]([O:79][C:80]([CH3:82])=[O:81])[C@H:25]([CH3:78])[C:26]([CH2:28][C@@H:29]4[O:34][C@@:33]5([O:39][C@@H:38]([CH2:40][C:41]([O:43][C@H:44]6[C@H:57]([OH:58])[C@@H:56]([CH2:59][C:60]([CH:62]([C@H:64]([OH:70])/[CH:65]=[CH:66]/[C:67]([Cl:69])=[CH2:68])C)=[CH2:61])[O:55][C@@H:46]([C@@H:47]2[OH:54])[C@@H:45]6[CH3:71])=[O:42])[CH2:37][C@H:36]([O:72]C(C)=O)[CH2:35]5)[CH2:32][C@:31]([OH:77])([CH3:76])[CH2:30]4)=[CH2:27])=[O:22])[CH2:17][C@H:16]([O:84][CH3:85])[CH2:15]3)[CH2:12][C@@H:11]([OH:86])[CH2:10]1.[CH3:87][OH:88]>>[CH3:1][C@H:2]1[C@H:51]([OH:52])[CH2:50][C@:48]2([OH:53])[O:49][C@H:3]1[CH2:4][CH2:5][CH2:6][CH:7]=[CH:8][C@H:9]1[O:88][C@:87]3([O:19][CH:18]([CH2:20][C:21]([C@@H:23]([CH3:83])[C@H:24]([O:79][C:80]([CH3:82])=[O:81])[C@@H:25]([CH3:78])[C:26]([CH2:28][C@H:29]4[O:34][C@:33]5([O:39][CH:38]([CH2:40][C:41]([O:43][C@H:44]6[C@H:57]([OH:58])[C@@H:56]([CH2:59][C:60]([CH2:62][C@@H:64]([OH:70])/[CH:65]=[CH:66]/[C:67]([Cl:69])=[CH2:68])=[CH2:61])[O:55][CH:46]([C@H:47]2[OH:54])[C@@H:45]6[CH3:71])=[O:42])[CH2:37][C@@H:36]([OH:72])[CH2:35]5)[CH2:32][C@@:31]([OH:77])([CH3:76])[CH2:30]4)=[CH2:27])=[O:22])[CH2:17][C@@H:16]([O:84][CH3:85])[CH2:15]3)[CH2:12][C@H:11]([OH:86])[CH2:10]1

Participants

Reactant 2

HCID 887Methanol2×

HCID 44368838HCID 44368838, compound

Product 1

HCID 6479881Spongistatin 3Yield 6%

Procedure

The cell growth inhibitory (P388 leukemia) dichloromethane fraction prepared from a 400 kg (wet wt) scaleup recollection (1988) of Spongia sp conducted in the Republic of Maldives was separated by a series of steric exclusion and partition chromatographic steps employing SEPHADEX LH-20 to obtain P388 active fractions reminiscent of spongistatin 1. A careful HPLC sequence using C-8 SILICA GEL (PREPEX and ULTREMEX) and 1:1 methanol water to 5:5:8 methanol-acetonitrile-water afforded 4.34 mg (1.08×10-6 % yield) of amorphous spongistatin 2: mp 140°-141° C.; [α]D +24.5°,(C 0.39, CH3OH); UV (CH3OH, log ε) λ, 220 (4.21), λ, 273 (2.95) nm; IR (film) 3426, 2937, 1736, 1651, 1603, 1381, 1234, 1177, 1086 cm-1, high resolution FABMS m/z 1227.6040 [M+K]+ corresponding to C63H96O21K (calcd mass 1227.6082). In contrast to that of spongistatin 1, no [M-35]+ ion was found. Spongistatin 3 was also obtained (2.69 mg, 6×10-8 % yield) as a colorless and noncrystalline powder; mp 148°-149° C.; [α]D +28.1° (c 0.15, CH3OH); UV (CH3OH, log ε) λ, 226 (3.14), λ268 (2.24) nm; IR (film) 3426, 2934, 1734, 1653, 1591, 1387, 1231, 1173, 1090 cm-1 ; HRFAB ms, m/z 1219.5556 [M+K]+ corresponding to C61H93ClO20K (calcd mass 1219.5584).

Sources & evidence

ORD record: ord-68e9d8fba5884c03bd3a033f22c54ea2
Source dataset: uspto-grants-1994_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05328929

Reaction notes

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