187277-46-9

Usage

Uses

Used in Anticancer Applications:
IROFULVEN is used as an antineoplastic agent for the treatment of various types of cancer. It is particularly effective in inhibiting the growth of solid tumors by disrupting DNA synthesis and triggering apoptosis in cancer cells. This makes IROFULVEN a promising pharmaceutical candidate for cancer therapy.
Used in Pharmaceutical Industry:
In the pharmaceutical industry, IROFULVEN is used as a key component in the development of anticancer drugs. Its ability to target and destroy cancer cells while minimizing damage to healthy cells makes it a valuable asset in the creation of novel cancer treatments.
Used in Research and Development:
IROFULVEN is also utilized in research and development for the study of cancer biology and the development of new cancer therapies. Its unique mechanism of action provides valuable insights into the processes underlying cancer cell growth and death, which can be applied to the design of more effective treatments.

Upstream product

• 50-00-0 formaldehyd 
• 33781-60-1 (R)-6’-hydroxy-2’,4’,6’-trimethylspiro[cyclopropane-1,5’-inden]-7’(6’H)-one 
• 33781-60-1 acylfulvene 
• 1149-99-1 illudin S 

Downstream Products

• 501426-42-2 6-ethyl-2,5,7-trimethyl-1-methylene-1H-inden-4-ol 

Relevant academic research and scientific papers

A rapid synthesis of hydroxymethylacylfulvene (HMAF) using the allenic Pauson-Khand reaction. A synthetic approach to either enantiomer of this illudane structure

An allenic Pauson-Khand reaction has been employed in the preparation of (±)-hydroxymethylacylfulvene (HMAF), an anticancer agent that is currently in Phase II clinical trials for a variety of solid tumor types. The synthesis is effected in 11 steps from commercially available starting materials. In addition, an asymmetric route to the title compound has been established by intersecting the racemic synthesis with an enantiomerically pure intermediate. The preparation of the enantiomerically pure intermediate involved the Sharpless asymmetric dihydroxylation (AD) of a trisubstituted olefin of an enyne system. This approach provides access to both enantiomers of HMAF simply by changing the ligands in the Sharpless AD reaction. Optimized conditions for the stereospecific synthesis of E or Z trisubstituted enynes from an aliphatic ketone using either Peterson olefination or Horner-Wadsworth-Emmons protocols are reported. Finally, a better understanding of the stereoelectronic requirements of the allenic P-K reaction is recognized.

ILLUDIN ANALOGS, USES THEREOF, AND METHODS FOR SYNTHESIZING THE SAME

This invention provides illudin derivatives, intermediates, preparation methods, pharmaceutical compositions and uses thereof. Specific examples include novel synthetic routes to prepare illudin derivatives and an illudin derivative having a positive optical rotation, which has therapeutic value.

Enantioselective total synthesis of (-)-acylfulvene and (-)-irofulven

(Chemical Equation Presented) We report our full account of the enantioselective total synthesis of (-)-acylfulvene (1) and (-)-irofulven (2), which features metathesis reactions for the rapid assembly of the molecular framework of these antitumor agents. We discuss (1) the application of an Evans Cu-catalyzed aldol addition reaction using a strained cyclopropyl ketenethioacetal, (2) an efficient enyne ring-closing metathesis cascade reaction in a challenging setting, (3) the reagent IPNBSH for a late-stage reductive allylic transposition reaction, and (4) the final RCM/dehydrogenation sequence for the formation of (-)-acylfulvene (1) and (-)-irofulven (2).

Enantioselective total synthesis of (-)-acylfulvene and (-)-irofulven

(Chemical Equation Presented) Antitumor agents (-)-acylfulvene and (-)-irofulven are prepared in an approach that employs the powerful enyne ring-closing metathesis reaction to secure the spiro-bicyclic AB rings. Other key features of this synthesis include an efficient aldol-based introduction of the stereocenter at C2, a diazene-mediated reductive allylic transposition, and a ring-closing metathesis/oxidation sequence.

Synthesis of [3H]-illudin S, [3H]-acylfulvene, [3H]and[14C]- hydroxymethylacylfulvene (MGI 114)

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.

Total synthesis of hydroxymethylacylfulvene, an antitumour derivative of illudin S

(±)-Hydroxymethylacylfulvene is synthesized in 14 steps from 4-hydroxy-5-methyl-2-cyclopenten-1-one and 1-acetyl-1-(diazoacetyl)cyclopropane in 15% overall yield.