Acetone → 10aH-2,12a-Methano-1H,4H-cyclopropa(5,6)(1,3)dioxolo(2',3')cyclopenta(1',2':9,10)cyclodeca(1,2-d)(1,3)dioxin-15-one, 1a,2,7a,13,14,14a-hexahydro-1,1,6,6,9,9,11,13-octamethyl-, (1aR-(1aalpha,2alpha,7aalpha,7bR*,10aalpha,12aalpha,13alpha,14aalpha))-

HRID 2224677Notes

Reaction equation

HRID 2224677 reaction equation
[CH3:1][C@H:2]1[C@:14]23[CH:17]=[C:18]([CH3:21])[C@H:19]([OH:20])[C@@:13]2([OH:22])[C@H:12]([OH:23])[C:11]([CH2:24][OH:25])=[CH:10][C@H:9]([C:15]3=[O:16])[C@@H:5]2[C:6]([CH3:8])([CH3:7])[C@@H:4]2[CH2:3]1.O.[C:27]1(C)[CH:32]=CC(S(O)(=O)=O)=C[CH:28]=1.[CH3:38][C:39]([CH3:41])=O>>[CH3:1][CH:2]1[C:14]23[CH:17]=[C:18]([CH3:21])[CH:19]4[O:20][C:39]([CH3:41])([CH3:38])[O:22][C:13]24[CH:12]2[C:11]([CH2:24][O:25][C:27]([CH3:32])([CH3:28])[O:23]2)=[CH:10][CH:9]([C:15]3=[O:16])[CH:5]2[C:6]([CH3:8])([CH3:7])[CH:4]2[CH2:3]1

Participants

4

Reactant 3

HCID 180AcetoneHCID 442042IngenolHCID 521998p-Toluenesulfonic acid monohydrate

Product 1

HCID 15708110aH-2,12a-Methano-1H,4H-cyclopropa(5,6)(1,3)dioxolo(2',3')cyclopenta(1',2':9,10)cyclodeca(1,2-d)(1,3)dioxin-15-one, 1a,2,7a,13,14,14a-hexahydro-1,1,6,6,9,9,11,13-octamethyl-, (1aR-(1aalpha,2alpha,7aalpha,7bR*,10aalpha,12aalpha,13alpha,14aalpha))-

Procedure

Ingenol can be converted to ingenol-3,4-acetonide by treatment with 4-toluenesulphonic acid hydrate and acetone to give ingenol-3,4:5,20-diacetonide followed by treatment with perchloric acid in methanol or zinc bromide in dichloromethane and methanol according to the method of Opferkuch et al. (1981). Ingenol-3,4-acetonide could be converted to ingenol-3,4-acetonide-20-trityl ether by treatment with trityl chloride and 4-(N,N-dimethylamino)pyridine in dry pyridine, acylated in an analogous manner to that described in Example 1 or Example 3 to give the ingenol-3,4-acetonide-20-trityl ether 5-acylate then treated with methanolic perchloric acid according to the method of Example 15 or Example 18 to give the ingenol 5-acylate. The ingenol 5-acylate could then be converted to the ingenol-3,4-acetonide 5-acylate by treatment with 4-toluenesulphonic acid hydrate and acetone according to the method of Opferkuch et al. (1981). The ingenol-3,4-acetonide 5-acylate could be converted to the 20-chloro-20-deoxy-3,4-acetonide 5-acylate by the method of Example 15.

Sources & evidence

ORD record
ord-41fa84a8394a42439fd264eda940fe63
Source dataset
uspto-grants-2008_05
Patent number
US07378445B2

Reaction notes

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