Total synthesis of (+)-ampullicin and (+)-isoampullicin: two fungal metabolites with growth regulatory activity isolated from Ampulliferina sp. 27.
The total synthesis of the growth regulators (+)-ampullicin 1 and (+)-isoampullicin 2 from (R)-(-)-carvone 5 was accomplished by application of an 18-step sequence with 4.5% overall yield. The crucial step of the synthetic strategy lies on the internal displacement of tosylate 13 by means of the lactone enolate. In this way, access was opened to the tricyclic core present in these biologically active sesquiterpenic amides. A Horner-Emmons reaction between the carbaldehyde 16 and the phosphonate 22 led us to the stereoselective preparation of (+)-ampullicin 1. Standard transformation of 1 into the thermodynamically more stable geometric isomer (+)-isoampullicin 2 was trivial. The absolute configuration of both amides was established by X-ray analysis of a sample of synthetic (+)-isoampullicin 2.
Bermejo
F A
FA
Departamento de Química Orgánica, Facultad de Ciencias Química, Universidad de Salamanca, Spain. fcobmjo@gugu.usal.es
Rico-Ferreira
R
R
Bamidele-Sanni
S
S
García-Granda
S
S
D018360:Crystallography, X-Ray; D005658:Fungi / Q000737:chemistry*; D006133:Growth Substances / Q000138:chemical synthesis* / Q000737:chemistry; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry; D012717:Sesquiterpenes / Q000138:chemical synthesis* / Q000737:chemistry
D006133:Growth Substances; D007202:Indicators and Reagents; D011758:Pyrroles; D012717:Sesquiterpenes; C443718:ampullicin