| 1. |
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| 2. |
- Verotta, L, et al.
(författare)
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Modulation of chemoselectivity by protein additives. Remarkable effects in the oxidation of hyperforin
- 2004
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Ingår i: Journal of Organic Chemistry. - : American Chemical Society (ACS). - 1520-6904 .- 0022-3263. ; 69:23, s. 7869-7874
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Tidskriftsartikel (refereegranskat)abstract
- Protein additives have a dramatic effect on the H2O2 oxidation of hyperforin, either protecting the enolized phloroglucinol core from oxidation (human albumin) or promoting (HRP and ovalbumin) reaction pathways derived from the intermediacy of the enollactone 4, a minor component of the oxidation mixture in the absence of protein additives. To rationalize the exquisite specificity of several steps and their mechanistic oddity, an organocatalytic effect is postulated. The use of protein additives allows a straightforward and multigram preparation of the enollactone 6, an interesting multifunctionalized scaffold for bioactivity induction and/or modulation.
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| 3. |
- Verotta, L, et al.
(författare)
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Oxidative fragmentation of the bridged beta-triketone core of hyperforin
- 2004
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Ingår i: European Journal of Organic Chemistry. - : Wiley. - 1434-193X .- 1099-0690. ; 2004:6, s. 1193-1197
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Tidskriftsartikel (refereegranskat)abstract
- The beta-triketone core of the antidepressant phloroglucinol hyperforin (1) undergoes a series of peroxide-induced oxidative rearrangements leading to compound 5, which is formed by opening of ring A, and compound 6, which is formed by removal of the C-1 carbonyl bridge. A mechanistic rationale for this process is proposed. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004).
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| 4. |
- Verotta, L, et al.
(författare)
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Synthesis and biological evaluation of hyperforin analogues. Part I. Modification of the enolized cyclohexanedione moiety
- 2002
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Ingår i: Journal of Natural Products. - : American Chemical Society (ACS). - 0163-3864 .- 1520-6025. ; 65:4, s. 433-438
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Tidskriftsartikel (refereegranskat)abstract
- Modification of the St. John's wort acylphloroglucinol constituent, hyperforin (1), by acylation, alkylation, and oxidation resulted in detrimental effects on the inhibition of the synaptosomal accumulation of serotonin, showing the existence of definite structure-activity relationships in this in vitro test system and highlighting the role of the enolized cyclohexanedione moiety for activity on neurotransmitter reuptake.
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| 5. |
- Appendino, G, et al.
(författare)
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Structure-activity relationships of ring C-secotaxoids. 1. Acylative modifications
- 2004
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Ingår i: Journal of Natural Products. - : American Chemical Society (ACS). - 0163-3864 .- 1520-6025. ; 67:2, s. 184-188
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Tidskriftsartikel (refereegranskat)abstract
- The acylative modification of IDN 5390 (3a), a 7,8-secotaxoid under preclinical development, was investigated. A modest decrease of potency was observed upon acylation of the primary and the enolic hydroxyls, suggesting that, just like in paclitaxel, the hydroxyl groups in the upper right-hand sector are not critical for cytotoxicity. The activity of these analogues, and especially of the chemically robust carbonates 3c and 3d, makes it unlikely that the activity of IDN 5390 is due to in vivo oxidation to a fledgling 7-aldehyde and re-aldolization to the corresponding taxane derivative.
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| 6. |
- Appendino, G, et al.
(författare)
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The reductive fragmentation of 7-hydroxy-9,10-dioxotaxoids.
- 2003
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Ingår i: European Journal of Organic Chemistry. - : Wiley. - 1434-193X .- 1099-0690. ; 2003:22, s. 4422-4431
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Tidskriftsartikel (refereegranskat)abstract
- The retro-aldol reductive fragmentation of different structural types of 7-hydroxy-9,10-dioxotaxoids was investigated, showing that the reaction is typical of taxanes and requires cerium(III) promotion with NaBH4 in protic medium and alkylboron (aluminium) hydrides in aprotic solvents. The resulting 7,8-seco-taxanes are key intermediates for the synthesis of a novel class of anticancer taxanes endowed with a unique pattern of in vivo biological activity. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
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| 7. |
- Danieli, B, et al.
(författare)
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Synthesis and biological evaluation of paclitaxel-thiocoichicine hybrids
- 2004
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Ingår i: Chemistry and Biodiversity. - : Wiley. - 1612-1872 .- 1612-1880. ; 1:2, s. 327-345
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Tidskriftsartikel (refereegranskat)abstract
- The bifunctional taxoid-colchicinoid hybrids 6-8 were synthesized and evaluated in assays of cytotoxicity and tubulin assembly/disassembly. All compounds showed a high degree of cytotoxicity, but, while 6 and 7 behaved as bifunctional tubulin binders not unlike an equimolecular mixture of taxol and thiocolchicine, 8 was surprisingly devoid of tubulin activity, acting on a distinct and yet to identify molecular target.
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