Trioxsalen: Difference between revisions
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The synthesis of the [[psoralen]] containing a methyl rather than a methoxy group on the aromatic ring starts with construction of the [[coumarin]] ring. |
The synthesis of the [[psoralen]] containing a methyl rather than a methoxy group on the aromatic ring starts with construction of the [[coumarin]] ring. |
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[[File:Trioxsalen synthesis.svg|thumb|center|700px|Trioxsalen synthesis:<ref>{{Cite DOI|10.1021/jo01060a028}}</ref> Kurt D Kaufman {{US patent|3201421}}]] |
[[File:Trioxsalen synthesis.svg|thumb|center|700px|Trioxsalen synthesis:<ref>{{Cite DOI|10.1021/jo01060a028}}</ref> Kurt D Kaufman {{US patent|3201421}}]] |
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[[Knoevenagel condensation]] of [[malonic acid]] with the substituted [[salicylaldehyde]] ('''1''') affords initially the unsaturated acid '''2'''. This is then cyclised to the coumarin '''3''' without prior purification. Decarboxylation completes preparation of the coumarin ring. Alkylation of the phenol by means of [[allyl bromide]] gives the allyl ether ('''5'''). This is converted to the C-allyl compound |
[[Knoevenagel condensation]] of [[malonic acid]] with the substituted [[salicylaldehyde]] ('''1''') affords initially the unsaturated acid '''2'''. This is then cyclised to the coumarin '''3''' without prior purification. Decarboxylation completes preparation of the coumarin ring. Alkylation of the phenol by means of [[allyl bromide]] gives the allyl ether ('''5'''). This is converted to the C-allyl compound by the thermal [[Claisen rearrangement]]; acetylation with [[acetic anhydride]] affords '''6'''. [[Bromination]] followed by [[saponification]] of the acetate leads to the dibromophenol ('''7'''). Solvolysis of this compound in base leads to the displacemnt of halogen by phenoxide to give the [[dihydrofuran]] ('''8'''). |
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== References == |
== References == |
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Revision as of 04:03, 17 April 2015
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| Names | |
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| IUPAC name
2,5,9-trimethyl-7H-furo[3,2-g]chromen-7-one
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| Identifiers | |
3D model (JSmol)
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| ChEBI | |
| ChEMBL | |
| ChemSpider | |
| DrugBank | |
| ECHA InfoCard | 100.021.327 |
| KEGG | |
PubChem CID
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| UNII | |
CompTox Dashboard (EPA)
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| Properties | |
| C14H12O3 | |
| Molar mass | 228.24328 |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Trioxsalen (trimethylpsoralen, Trioxysalen or Trisoralen) is a furanocoumarin and a psoralen derivative. It is obtained from several plants, mainly Psoralea corylifolia. Like other psoralens it causes photosensitization of the skin. It is administered either topically or orally in conjunction with UV-A (the least damaging form of ultraviolet light) for phototherapy treatment of vitiligo[1] and hand eczema.[2] After photoactivation it creates interstrand cross-links in DNA, which can cause programmed cell death unless repaired by cellular mechanisms. In research it can be conjugated to dyes for confocal microscopy and used to visualize sites of DNA damage.[3] The compound is also being explored for development of antisense oligonucleotides that can be cross-linked specifically to a mutant mRNA sequence without affecting normal transcripts differing at even a single base pair.[4]
Synthesis
The synthesis of the psoralen containing a methyl rather than a methoxy group on the aromatic ring starts with construction of the coumarin ring.
Knoevenagel condensation of malonic acid with the substituted salicylaldehyde (1) affords initially the unsaturated acid 2. This is then cyclised to the coumarin 3 without prior purification. Decarboxylation completes preparation of the coumarin ring. Alkylation of the phenol by means of allyl bromide gives the allyl ether (5). This is converted to the C-allyl compound by the thermal Claisen rearrangement; acetylation with acetic anhydride affords 6. Bromination followed by saponification of the acetate leads to the dibromophenol (7). Solvolysis of this compound in base leads to the displacemnt of halogen by phenoxide to give the dihydrofuran (8).
References
- ^ "Trioxsalen - Compound Summary". PubChem.
- ^ Van Coevorden, AM; Kamphof, WG; Van Sonderen, E; Bruynzeel, DP; Coenraads, PJ (2004). "Comparison of oral psoralen-UV-A with a portable tanning unit at home vs hospital-administered bath psoralen-UV-A in patients with chronic hand eczema: an open-label randomized controlled trial of efficacy". Archives of dermatology. 140 (12): 1463–6. doi:10.1001/archderm.140.12.1463. PMID 15611423.
- ^ Thazhathveetil, AK; Liu, ST; Indig, FE; Seidman, MM (2007). "Psoralen conjugates for visualization of genomic interstrand cross-links localized by laser photoactivation". Bioconjugate chemistry. 18 (2): 431–7. doi:10.1021/bc060309t. PMID 17373769.
- ^ Higuchi, M; Yamayoshi, A; Kobori, A; Yamaoka, T; Murakami, A (2005). "Synthesis and properties of photo-reactive antisense oligonucleotides containing 2'-O-psoralen-conjugated adenosine". Nucleic acids symposium series (2004). 49 (49): 331–2. doi:10.1093/nass/49.1.331. PMID 17150768.
- ^ Template:Cite DOI
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