8-Methoxypsoralen → 1-[5-[[Bis(4-methoxyphenyl)-phenylmethoxy]methyl]-4-hydroxyoxolan-2-yl]-5-methylpyrimidine-2,4-dione

HRID 745472Notes

Reaction equation

O1C=CC=C1.[C@@H:6]1([N:14]2[CH:22]=[C:20]([CH3:21])[C:18](=[O:19])[NH:17][C:15]2=[O:16])[O:13][C@H:10]([CH2:11][OH:12])[C@@H:8]([OH:9])[CH2:7]1.COC1C2OC(C=CC=2C=C2C=COC=12)=O.[CH3:39][O:40][C:41]1[CH:62]=[CH:61][C:44]([C:45](Cl)([C:54]2[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=2)[C:46]2[CH:51]=[CH:50][C:49]([O:52][CH3:53])=[CH:48][CH:47]=2)=[CH:43][CH:42]=1>>[CH3:21][C:20]1[C:18](=[O:19])[NH:17][C:15](=[O:16])[N:14]([CH:6]2[O:13][CH:10]([CH2:11][O:12][C:45]([C:44]3[CH:61]=[CH:62][C:41]([O:40][CH3:39])=[CH:42][CH:43]=3)([C:46]3[CH:51]=[CH:50][C:49]([O:52][CH3:53])=[CH:48][CH:47]=3)[C:54]3[CH:55]=[CH:56][CH:57]=[CH:58][CH:59]=3)[CH:8]([OH:9])[CH2:7]2)[CH:22]=1

Participants

Reactant 4

HCID 41148-Methoxypsoralen

HCID 5789Thymidine

HCID 8029Furan

HCID 968311,1'-(Chlorophenylmethylene)bis(4-methoxybenzene)

Product 1

HCID 6275541-[5-[[Bis(4-methoxyphenyl)-phenylmethoxy]methyl]-4-hydroxyoxolan-2-yl]-5-methylpyrimidine-2,4-dione

Procedure

For example, the furan-side monoadduct between thymidine and 8-methoxypsoralen, prepared as described above, is reacted with 4,4'-dimethoxytrityl chloride at room temperature in an appropriate anhydrous solvent to give the 5'-dimethoxytrityl thymidine:8-methoxypsoralen monoadduct. Following purification by high pressure liquid chromatography this compound is reacted with chloro-N,N diisopropylamino methoxyphosphine at room temperature in an appropriate solvent to give the 5'-dimethoxytritylthymidine phosphoramidite: 8-methoxypsoralen monoadduct. This compound is then used as an activated protected nucleoside phosphoramidite in a typical phosphite triester polynucleotide synthesis. The stereochemistry of the 8-methoxypsoralen moiety is correct (i.e. cis-syn) for subsequent crosslink formation when hybridized to the complementary sequence.

Sources & evidence

ORD record: ord-42170b6c677e4809acba641b4cf0fc88
Source dataset: uspto-grants-1986_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US04599303

Reaction notes

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