Synthesis of Bioactive Sesterterpenolides from ent-Halimic Acid. 15-Epi-ent-cladocoran A and B

Abstract

The bioactive sesterterpenoid gamma-hydroxybutenolides 15,18-bisepi-ent-Cladocoran A and B, 1 and 2, and 15-epi-ent-Cladocoran A and B, 57 and 55, were synthesized from ent-halimic acid. The synthesized sesterterpenolids 2, 55, 57, and 59 inhibited cellular proliferation (IC(50) congruent with 2 micro M) of a number of human leukaemic and solid tumor cell lines.

Halimane diterpenoids: sources, structures, nomenclature and biological activities

“…A structural characteristic of this group of compounds (208)(209)(210)(211)(212)(213)(214)(215)(216)(217)(218)(219) is that all of them show oxygenated functions at C5, except diasin (219, from Croton diasii), 176 which we include in this group precisely for not having any unsaturation in the decalin system ( Fig. 15, Table S4 †).…”

“…109,209 (3) Bioactive sesterterpenolides. 123,[210][211][212] (4) Sesterterpenolides and glycerophospholipids hybrid compounds. 213 (5) Rearranged derivatives: ent-labdanes, 214 abeopicrasanes 215 and propellanes.…”

Synthesis of an ent-Halimanolide from ent-Halimic Acid

“…Addition of 3-furyl lithium [10,11,12] to 12 gives a mixture of the hydroxy derivatives 13 and 14 . The C-12 configuration in 13 and 14 was established by comparation of their physical properties with the ones of similar compounds [13,14]. Oxidation of the mixture of 13 and 14 with TPAP gives 2 , -101.4 (c 0.2, CHCl 3 ), that was identical in all its physical properties to the natural compound 15,16-epoxy-12-oxo- ent -halima-5(10),13(16),14-trien-18,2β-olide, -151.5 (c 0.017, CHCl 3 ), already described [8].…”

Total Synthesis of (+)-Greek Tobacco Lactone

“…16 Alternative conditions involving the use of phosphoryl chloride in pyridine gave a 52% yield together with some endo-product. 17 In conclusion, a protecting-group-free total synthesis of (+)-Greek tobacco lactone (1) from aldehyde 3 was achieved in four steps and 34% overall yield (22% when diol 7 was recrystallized to improve the dr). 18 The starting aldehyde 3 can be prepared by our previously reported Mukaiyama-Michael methodology.…”