Synthesis, reactions and structure-activity relationships of 1-hydroxyspiro[2.5]cyclooct-4-en-3-ones: illudin analogs with in vitro cytotoxic activity.
1-Hydroxyspiro[2.5]cyclooct-4-en-3-ones-analogs of natural illudines--were prepared in good yields by cyclization of 1,3-dicarbonyl dianions or 1,3-bis-silyl enol ethers ('masked dianions') with 1,1-diacylcyclopropanes. Several spirocyclopropanes showed a significant antiproliferative activity against human leukemia HL60 cells in vitro. 1-Hydroxyspiro[2.5]cyclooct-4-en-3-ones represent highly reactive precursors of unstable spiro[5.2]cycloocta-4,7-dien-6-ones and reactions with a number of nucleophiles were studied.
Bose
Gopal
G
Institut für Chemie und Biochemie, Universität Greifswald, Soldmannstr. 16, 17487 Greifswald, Germany.
Bracht
Karin
K
Bednarski
Patrick J
PJ
Lalk
Michael
M
Langer
Peter
P
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D066298:In Vitro Techniques; D000081223:Polycyclic Sesquiterpenes; D012717:Sesquiterpenes / Q000737:chemistry / Q000494:pharmacology; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D000081223:Polycyclic Sesquiterpenes; D012717:Sesquiterpenes; D013141:Spiro Compounds; C052673:illudin M