Tumor inhibitors. LXXXVI. Structural elucidation of novel tumor-inhibitory sesquiterpene lactones from Eupatorium cuneifolium

Abstract

rated t o a small volume and acidified to pH 4 using 0.1 N HCl.The precipitate thus formed was collected by centrifugation, washed several times with water, and dried in vacuo to give 30% yield of the product, 6, as a brown powder, mp >300'. In 0.1 N NaOH XmRX were found at 380 nm (e 10,117) and 275 (23,690), and in 0.1 N HC1 a t 346 and 271 nm; nmr 9.10 (s, one proton, Hl), 7.75 (d, two protons, J = 8 cps, HV,W), 7.48 (d, two protons, J = 8 cps, HI,,S,j, 4.62 (t, a proton of glutamic acid), and 2.65 ppm (c, four protons of glutamic acid). Hydrolysis of 6 by HC1 in glacial HOAc gave P-6-COOH, p-aminobenzoic acid, and glutamic acid. Compound 5 was prepared in the same manner using p-aminobenzoic acid as the nucleophile. The product whichelutedat0.43 M NaClshowed kmsx in 0.1 N NaOHat380nm (e 10,507) and 275 (22,809), and in 0.1 N HCl a t 350 and 275 nm. On acid hydrolysis 5 gave P-6-COOH and p-aminobenzoic acid.Synthesis of 9-Oxoisohomopterioc Acid (11). A. Preparation of a-Amino-p-toluic Acid.-p-Carboxybenzaldehyde (1.5 g) and 1.2 g of hydroxylamine hydrochloride were dissolved in 20 ml of EtOH and brought to reflux; a clear solution was obtained. To this was added dropwise 1.7 g of NaOH dissolved in 7 ml of water, over a period of 0.5 hr. Water (0.5 ml) was then added to bring the suspension into solution. Refluxing was continued for an additional 15 min and the reaction mixture was poured into 100 ml of ice-cold 20% HC1. The precipitate was collected by filtration and recrystallized from ILIeOH: yield 1.1 g; mp 223-224'; nmr (DMSO) 7.9 (q, four protons, J = 7 cps, aromatic), 8.3(6, one proton), and 10.2 ppm (s, one proton, carboxyl).The above oxime (1 g) was dissolved in 100 ml of 95% EtOH, 100 mg of 5y0 Pd/C was added, and hydrogenation was carried out for 18 hr at 30 psi. Filtration and washing the residue with two 20-ml portions of hot glacial HOAc gave a solution which was evaporated t o dryness. The solid thus obtained was triturated with absolute EtOH and filtered, producing 850 mg of solid. This was crystallized from water to give the white crystalline a-amino-p-toluic acid: mp 294-295'; Xmsx 234 nm (H20); nmr (TFA) 4.15 (9, J = 6 cps), 7.3 (d, J = 8 cps, two protons adjacent to the aminomethyl group), and 7.9 ppm (d, J = 8 cps, two protons adjacent to the carboxyl group).Treatment of this material with diazomethane gave the corresponding methyl ester, whose high-resolution mass spectrum showed the molecular ion a t 164.0708 (calculated for CoHloNO1, 164.0711), again representing the loss of a hydrogen from the benzylic position.B. Synthesis of 9-Oxoisohomopteroic Acid (ll).-a-Aminop-toluic acid and 8 (1 mmol of each) were treated as usual. After deprotection and chromatography on DEAE cellulose C1-, 11 eluted as a single band at 0.22 M NaCl, and was recovered from the pooled peak in about 36% yield. The uv spectral data revealed kmn, at 370 nm (e 10,750) and 270 (25,240) and Amin a t 320 and 250 nm in 0.1 N NaOH; nmr 9.25 (s, one proton, Hl), 8.15 (d, two protons, J = 8 cps, Hv,v), 7.7 (d, two protons, ...

Sesquiterpenes and Other Constituents from Dendranthema zawadskii var. latilobum

“…In conclusion, seven new compounds (1-7) and 13 known compounds (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) were isolated from the aerial parts of D. zawadskii var. latilobum, and their structures were determined by spectroscopic analysis.…”

“…The coupling constants across the protons at positions H-5-H-7 (J 5,6 =J 6,7 =10.3 Hz) were equivalent to the literature values for a rare, naturally occurring cis-Δ 4,5 ,cis-Δ 9,10 -germacradiene-trans-12,6-olide. [15][16][17] The relative stereochemistry of 1 was determined by comparison of the spectral data of 1 with those recorded for other known cis,cis-dienetype sesquiterpene lactones such as eupacunin, eupacunolin and eurecurvin, [15][16][17] as well as from the nuclear Overhauser effect spectroscopy (NOESY) spectrum (Fig. 2).…”

Structural requirements for biological activity among antileukemic glaucarubolone ester quassinoids

“…The interesting structure-activity correlations among the bruceolide esters led us to investigate in more detail a second series of quassinoids. Glaucarubinone (6),4 a saturated ester of glaucarubolone (12),4 showed moderate activity against the P-388 system. Glaucarubinone was isolated from Pierreodendron kerstingii (Simaroubaceae) as shown in Scheme I, and its side chain and A ring were modified chemically to study the role which each plays in the antileukemic activity of the glaucarubolone esters.…”

“…The details of the spectrum and the presence of mass spectral fragment ions at m/e 247 and 151, which are common ions in the mass spectra of glaucarubolone and related compounds,5 con-Scheme I. Isolation of Glaucarubinone (6) from P. kerstingii Pierreodendron kerstingii Little (12 kg) 95% EtOH marc H20 (3 1. ) CHCI3 (4 X 5.5 1.)…”

“…7:3 ratio of higher Rf to lower Rf material as judged by NMR spectroscopy. Similarly, reduction of glaucarubinone (6) gave a crystalline product which was characterized as dihydroglaucarubinone (16) by elemental analysis and spectral data and which was shown by TLC to be a two-component mixture. Again, the NMR spectra of the resulting products showed differences in the methyl region which were consistent with stereoisomer formation via attack on both the a and the ß faces of ring A during reduction.…”