Ethyl 10α-hy-droxy-4,9-dimethyl-14-oxo-3,8,15-trioxa-tetra-cyclo-[10.3.0.0.0]penta-decane-13-spiro-5'-pyrazole-3'-carboxyl-ate.

The ten-membered ring in the title mol-ecule, CHClNO, adopts an approximate chair-chair conformation, whereas the five-membered furan and pyrazole rings display envelope conformations. The mean plane of the furan ring is almost perpendicular to that of the pyrazole ring, as indicated by the dihedral angle between them of 86.45 (9)°.

Synthesis and biological evaluation of 9α- and 9β-hydroxyamino-parthenolides as novel anticancer agents.

A series of 9α-hydroxyamino-parthenolides 3-10, 9β-hydroxyamino-parthenolides 11-13 and 9α-hydroxy-1β,10α-epoxyamino-parthenolides 15-19 were efficiently synthesized starting from 9α-hydroxyparthenolide 1 and 9β-hydroxyparthenolide 2, which were isolated from Anvillea radiata. Compounds 1-13 and 15-19 were evaluated for their in vitro anticancer activity by the MTT colorimetric assay against one murine and six human cancer cell lines. This work provides new details about the structural requisites for anticancer activity.

(1S,2R,3R,6R,7S,8R,10S,11S)-13-{[4-(4-Chloro-phen-yl)piperazin-1-yl]meth-yl}-10-hy-droxy-4,9-dimethyl-3,8,15-trioxatetra-cyclo-[10.3.0.0(2,4).0(7,9)]penta-decan-14-one.

The title compound, C(25)H(33)ClN(2)O(5), was synthesized from 9α-hy-droxy-parthenolide (9α-hy-droxy-4,8-dimethyl-12-methyl-ene-3,14-dioxatricyclo-[9.3.0.

10α-Hy-droxy-13-{[4-(2-hy-droxy-phen-yl)piperazin-1-yl]meth-yl}-4,9-dimethyl-3,8,15-trioxatetra-cyclo-[10.3.0.0(2,4).0(7,9)]penta-decan-14-one.

The title compound, C(25)H(34)N(2)O(6), was synthesized from 9α-hy-droxy-parthenolide (9α-hy-droxy-4,8-dimethyl-12-methyl-ene-3,14-dioxatricyclo-[9.3.0.

12-{[4-(2-Fluoro-phen-yl)piperazin-1-yl]-meth-yl}-9α-hy-droxy-4,8-dimethyl-3,14-dioxatricyclo-[9.3.0.0]tetra-dec-7-en-13-one.

The title compound, C(25)H(33)FN(2)O(4), was synthesized from 9α-hy-droxy-parthenolide (9α-hy-droxy-4,8-dimethyl-12-methyl-ene-3,14-dioxatricyclo-[9.3.0.

10α-Hy-droxy-13-{[4-(4-meth-oxy-phen-yl)piperazin-1-yl]meth-yl}-4,9-dimethyl-3,8,15-trioxatetra-cyclo-[10.3.0.0.0]penta-decan-14-one.

The title compound, C(26)H(36)N(2)O(6), was synthesized from 9α-hy-droxy-parthenolide (9α-hy-droxy-4,8-dimethyl-12-methylen-3,14-dioxa-tricyclo-[9.3.0.

9α-Hy-droxy-12-{[4-(4-meth-oxy-phen-yl)piperazin-1-yl]meth-yl}-4,8-dimethyl-3,14-dioxatricyclo-[9.3.0.0]tetra-dec-7-en-13-one.

The title compound, C(26)H(36)N(2)O(5), was synthesized from 9α-hy-droxy-parthenolide (9α-hy-droxy-4,8-dimethyl-12-methyl-ene-3,14-dioxatricyclo-[9.3.0.

9β-Hy-droxy-6,9-dimethyl-3-methyl-ene-3a,4,8,9,9a,9b-hexa-hydro-azuleno[4,5-b]furan-2(3H)-one.

The title compound, C(15)H(18)O(3), was synthesized from 9α-hy-droxy-parthenolide (9α-hy-droxy-4,8-dimethyl-12-methylen-3,14-dioxa-tricyclo-[9.3.0.

10α-Hy-droxy-4,9-dimethyl-13-(morph-o-lin-4-ylmeth-yl)-3,8,15-trioxatetra-cyclo-[10.3.0.0.0]penta-decan-14-one.

The title compound, C(19)H(29)NO(6), was synthesized from 9α-hy-droxy-parthenolide (9α-hy-droxy-4,8-dimethyl-12-methyl-ene-3,14-dioxatricyclo-[9.3.0.

10α-Hy-droxy-4,9-dimethyl-13-(pipyridin-1-ylmethyl)-3,8,15-trioxatetra-cyclo-[10.3.0.0.0]tetra-decan-14-one.

The title compound, C(20)H(31)NO(5), was synthesized from 9α-hy-droxy-parthenolide (9α-hy-droxy-4,8-dimethyl-12-methylen-3,14-dioxa-tricyclo-[9.3.0.

10α-Hy-droxy-4,9-dimethyl-13-[(4-phenyl-piperazin-1-yl)meth-yl]-3,8,15-trioxatetra-cyclo-[10.3.0.0.0]tetra-decan-14-one.

The title compound, C(25)H(34)N(2)O(5), was synthesized from 9α-hy-droxy-parthenolide (9α-hy-droxy-4,8-dimethyl-12-methyl-ene-3,14-dioxatricyclo-[9.3.0.

(1S,2R,3R,8R,10S)-3-Chloro-2,8-dihy-droxy-3,7-dimethyl-11-methyl-idene-13-oxabicyclo-[8.3.0]tridec-6-en-12-one.

The title compound, C(15)H(21)ClO(4), was synthesized from 9α-hy-droxy-parthenolide (9α-hy-droxy-4,8-dimethyl-12-methylen-3,14-dioxatricyclo-[9.3.0.

9-Hy-droxy-4,8-dimethyl-12-(pyrrolidin-1-ylmeth-yl)-3,14-dioxatricyclo-[9.3.0.0]tetra-dec-7-en-13-one.

The title compound, C(19)H(29)O(4), was synthesized from 9α-hy-droxy-parthenolide (9α-hy-droxy-4,8-dimethyl-12-methylen-3,14-dioxatricyclo-[9.3.0.

9-Hy-droxy-4,8-dimethyl-12-(piperidin-1-ylmeth-yl)-3,14-dioxatricyclo-[9.3.0.0]tetra-dec-7-en-13-one.

The title compound, C(20)H(31)NO(4), was synthesized from 9α-hy-droxy-parthenolide (9α-hy-droxy-4,8-dimethyl-12-methylen-3,14-dioxa-tricyclo-[9.3.0.

10α-Hy-droxy-4,9-dimethyl-13-[(pyrrol-idin-1-yl)meth-yl]-3,8,15-trioxatetra-cyclo-[10.3.0.0.0]penta-decan-14-one.

The title compound, C(19)H(29)NO(5), was synthesized from 9α-hy-droxy-parthenolide (9α-hy-droxy-4,8-dimethyl-12-methyl-ene-3,14-dioxatricyclo-[9.3.0.

5,9-Dihy-droxy-9-methyl-3,6-dimethyl-ene-3a,4,5,6,6a,7,8,9,9a,9b-deca-hydro-azuleno[4,5-b]furan-2(3H)-one.

The title compound, C(15)H(20)O(4), was synthesized from 9α-hy-droxy-parthenolide (9α-hy-droxy-4,8-dimethyl-12-methyl-ene-3,14-dioxatricyclo-[9.3.0.

(Z)-6-Hy-droxy-1a,5-dimethyl-8-[(morpholin-4-yl)meth-yl]-2,3,6,7,7a,8,10a,10b-octa-hydro-oxireno[2',3':9,10]cyclo-deca-[1,2-b]furan-9(1aH)-one.

The title compound, C(19)H(29)NO(5), was synthesized from 9α-hy-droxy-parthenolide (9α-hy-droxy-4,8-dimethyl-12-methylen-3,14-dioxatricyclo-[9.3.0.

5,8-Dimethyl-3-methyl-ene-2-oxo-3,3a,4,5,5a,6,8a,8b-octa-hydro-2H-1-oxa-s-indacene-5-carbaldehyde.

The title compound, C(15)H(18)O(3), was synthesized from 9α-hy-droxy-parthenolide (9α-hy-droxy-4,8-dimethyl-12-methyl-ene-3,14-dioxatricyclo-[9.3.0.

12-Anilinomethyl-9α-hy-droxy-4,8-dimethyl-3,14-dioxatricyclo-[9.3.0.0]tetra-dec-7-en-13-one.

The title compound, C(21)H(27)NO(4), was synthesized from 9α-hy-droxy-parthenolide, which was isolated from the chloro-form extract of the aerial parts of Anvillea radiata. The asymmetric unit contains two independent mol-ecules. In each, the ten-membered ring displays an approximative chair-chair conformation.

9α-Acet-oxy-1β,10α-ep-oxy-parthenolide.

The title compound, C(17)H(22)O(6), was semi-synthesized from 9-hy-droxy-arthenolide, which was isolated from the chloro-form extract of the aerial parts of Anvillea radiata. The mol-ecule contains fused five- and ten-membered rings: the five-membered lactone ring has a twisted conformation, whereas the ten-membered ring displays an approximate chair-chair conformation. The dihedral angle between the rings is 24.

9β-Hy-droxy-1β,10α-ep-oxy-parthenolide.

The title compound, C(15)H(20)O(5) (systematic name: 5-hydroxy-1a,4a-dimethyl-7-methyleneperhydrodioxireno[5,6:9,10]cyclo-deca[1,2-b]furan-8-one), was obtained by the reaction of 3-chloro-perbenzoic acid with 9β-hy-droxy-parthenolide. The five-membered ring adopts a twist conformation, whereas the ten-membered ring displays an approximate chair-chair conformation. In the crystal structure, mol-ecules are linked into chains propagating along the b axis by inter-molecular O-H⋯O hydrogen bonds.

2-Isopropyl-4-meth-oxy-5-methyl-phenyl benzoate.

The title compound, C(18)H(20)O(3), a hemisynthetic product, was obtained by the reaction of benzoyl chloride and p-methoxy-thymol. The structure comprises two benzene rings bridged by a carboxyl group; the dihedral angle between the rings is 73.54 (8)°.