Synthesis of the 1,6,8-trioxadispiro[4.1.5.2]tetradec-11-ene ring system present in the spirolide family of shellfish toxins and its conversion into a 1,6,8-trioxadispiro[4.1.5.2]-tetradec-9-en-12-ol via base-induced rearrangement of an epoxide.
The synthesis of the 1,6,8-trioxadispiro[4.1.5.2]tetradec-11-enes 12 present in the shellfish toxins spirolides B and D 2, is reported. The two spirocentres were constructed via iterative radical oxidative cyclization of hydroxyalkyl dihydropyran 14 and hydroxyalkyl spiroacetal 13 using iodobenzene diacetate and iodine. This procedure initially afforded a 1 : 1 : 1 : 1 mixture of bis-spiroacetals 12a : 12b : 12c : 12d, however subsequent acid catalysed equilibration afforded a 3 : 1 : 0.9 thermodynamic mixture of 12a : 12b : 12c. The major bis-spiroacetal 12a underwent stereoselective epoxidation using dimethyldioxirane to alpha-epoxide 33a. Subsequent base induced rearrangement of this epoxide 33a using lithium diethylamide in pentane afforded allylic alcohol 34a, that was converted to the more thermodynamically favoured homoallylic alcohol 11a upon treatment with lithium pyrrolidinylamide in tetrahydrofuran. Homoallylic alcohol 11a possesses a hydroxyl group at C-12 as required for introduction of the tertiary alcohol group present at this position in spirolides B 1 and D 2.
Brimble
Margaret A
MA
Department of Chemistry, University of Auckland, 23 Symonds St., Auckland, New Zealand. m.brimble@auckland.ac.nz
Furkert
Daniel P
DP
D000080:Acetals / Q000737:chemistry; D000475:Alkenes / Q000138:chemical synthesis* / Q000737:chemistry; D000818:Animals; D004852:Epoxy Compounds / Q000737:chemistry*; D008387:Marine Toxins / Q000737:chemistry*; D008968:Molecular Conformation; D012758:Shellfish; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000737:chemistry
C496747:1,6,8-trioxadispiro(4.1.5.2)-tetradec-9-en-12-ol; C496746:1,6,8-trioxadispiro(4.1.5.2)tetradec-11-ene; D000080:Acetals; D000475:Alkenes; D004852:Epoxy Compounds; D008387:Marine Toxins; D013141:Spiro Compounds; C467770:spirolide B; C467769:spirolide D