28282-65-7Relevant academic research and scientific papers
Synthesis of [3H]-illudin S, [3H]-acylfulvene, [3H]and[14C]- hydroxymethylacylfulvene (MGI 114)
McMorris, Trevor C.,Yu, Jian,Herman, David M.,Kelner, Michael J.,Dawe, Robin,Minamida, Akira
, p. 279 - 285 (2007/10/03)
Tritiated derivatives of the toxic sesquiterpene illudin S (1) have been prepared by fermentation of Omphalotus illudens in the presence of [3H]- sodium acetate. [3H]-illudin S was converted to antitumor [3H]-acylfulvene (4) by treatment with dilute sulfuric acid. Antitumor [14C]- hydroxymethylacylfulvene (5) was best prepared by reacting acylfulvene with [14C]-paraformaldehyde in dilute sulfuric acid.
An approach toward the Illudin family of sesquiterpenes using the tandem cyclization - Cycloaddition reaction of rhodium carbenoids
Padwa,Curtis,Sandanayaka
, p. 1317 - 1325 (2007/10/03)
The Rh(II)-catalyzed reaction of 1-acetyl-1-(diazoacetyl)cyclopropane with 5,5-dimethylcyclopentenone afforded the product of a 1,3-dipolar cycloaddition in high yield. The reaction involves formation of a rhodium carbenoid and subsequent transannular cyclization of the electrophilic carbon onto the adjacent keto group to generate a five-membered cyclic carbonyl ylide which undergoes a subsequent 1,3-dipolar cycloaddition reaction. The regiochemical results encountered can be rationalized on the basis of FMO considerations. Treatment of the cycloadduct with p-toluene-sulfonic acid results in loss of water followed by a subsequent acid-catalyzed cyclopropyl ketone rearrangement to give dihydrobenzofuran 21. The product distribution derived from the SmI2-induced reduction of the dipolar cycloadduct was found to depend on the reaction conditions. Under kinetic conditions, the reduction resulted in opening of the cyclopropyl ring adjacent to the carbonyl group. However, under thermodynamic conditions, cleavage of the oxy bridge corresponded to the major pathway. The cycloaddition-reduction protocol provides a rapid assembly of the basic core unit of ptaquilosin having most of the functionality in place. Generation of a carbanion adjacent to the oxy bridge leads to opening of the oxabicyclic ring system in a highly regioselective manner. A short synthesis of (±)-illudin M and the closely related isodehydroilludin M is described in which the key step involves a dipolar cycloaddition using a carbonyl ylide.
Total synthesis of (±)-illudin M
Kinder,Bair
, p. 6965 - 6967 (2007/10/02)
(+)-Illudin M (1) was synthesized in six steps starting from 1-acetyl-1-(diazoacetyl)cyclopropane (4) and 4-bromo-5,5-dimethyl-2-cyclopentenone (5). The key step of the synthesis featured a carbonyl ylide 1,3-dipolar cycloaddition reaction that was mediat
Structure-Activity Relationships of Illudins: Analogs with Improved Therapeutic Index
McMorris, Trevor C.,Kelner, Michael J.,Wang, Wen,Estes, Leita A.,Montoya, Mark A.,Taetle, Raymond
, p. 6876 - 6883 (2007/10/02)
Illudin S and M are extremely toxic sesquiterpenes produced by Omphalotus illudens.At low pH they behave as bifunctional alkylating agents, but at physiological pH they do not react with oxygen or nitrogen nucleophiles.Illudins react spontaneously with sulfur nucleophiles, gluthathione or cysteine, at or slightly below pH 7, and toxicity to HL 60 cells can be modulated by altering glutathione levels in cells.Analogs of illudin M, e.g. the deoxy and, particularly, the dehydro derivatives, are less reactive to thiols and correspondingly less toxic to HL 60 cells than the parent compound.Dehydroilludin M has been found to be quite effective at inhibiting tumor growth in vivo at doses well tolerated at athymic nude mice.
