Nucleosides. 117. Synthesis of 4-oxo-8-(β-D-ribofuranosyl)-3H-pyrazolo[1,5-a]-1,3,5-triazine (OPTR) via 3-amino-2N-carbamoyl-4-(β-D-ribofuranosyl)pyrazole (ACPR) derivatives

Reaction of 2-formyl-2-(2,3-O-isopropylidene-5-O-trityl-D-ribofuranosyl)acetonitrile (VII) with semicarbazide hydrochloride followed by sodium ethoxide treatment afforded an α,β-mixture of 3-amino-2N-carbamoyl-4-(2,3-O-isopropylidene-5-O-trityl-D-ribofuranosyl)pyrazole (IX). Conversion of IX to 4-oxo-8-(2,3-O-isopropylidene-5-O-trityl-D-ribofuranosyl)-3H-pyrazolo[1,5-a]-1,3,5-triazine (XIII) was achieved by treatment of IX with ethylorthoformate. The β-isomer IXb gave only the β-isomer XIIIb, and the α-isomer IXa was converted exclusively into the α-isomer XIIIa. Upon deprotection with 3% n-butanolic hydrogen chloride, both IXa and IXb gave the same mixture of the α- and β-isomers of 3-amino-2N-carbamoyl-4-(D-ribosyl)pyrazole, which were separated by chromatography. The syntheses of the hitherto unknown compounds, 3-amino-2N-carbamoylpyrazole (IVa) and its 4-methyl analog (IVb) are also reported. Experimental details of the synthesis of 3-amino-4-(2,3-O-isopropylidene-5-O-trityl-β-D-ribofuranosyl)pyrazole (XIIb), an important intermediate for “purine-like” C-nucleosides, are also described.     

A comparison of two methods for the preparation of 3-Deazapurine ribonucleosides

The reaction of the trimethylsilyl derivative of 4,6-dichloroimidazo[4,5-c]pyridine with 2,3,5-tri-O-benzoyl- D -ribofuranosyl bromide gave four nucleosides-the α- and β-anomers of the 1-isomer and the α- and β-anomers of the 3-isomer (3.9:2.7:1.5:1). In contrast, the fusion reaction of 4,6-dichloroimidazo[4,5-c ]pyridine with 1,2,3,5-tetra-O-acetyl-β- D -ribofuranose gave a high yield of the 1-β-isomer, which was converted to the known 3-deazaadenosine (4-amino-l-β- D -ribofuranosylimidazo[4,5-c]pyridine).     

Syntheses of 6-Amino-1-(β-D-ribofuranosyl)-1H-pyrazolo[3,4-d]-1,3-oxazin-4-one,an isostere of oxanosine,and the guanosine analog 6-amino-1-(β-d-ribofuranosyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one via ring closure of pyrazole-5-thioureido intermediates

6-Amino-1-(β-D-ribofuranosyl)-1H-pyrazolo[3,4-d]-1,3-oxazin-4-one ( 4 ), an isostere of the nucleoside antibiotic oxanosine has been synthesized from ethyl 5-amino-1-(2,3-O-isopropylidene-β-D-ribofuranosyl)pyrazole-4-carboxylate ( 6 ). Treatment of 6 with ethoxycarbonyl isothiocyanate in acetone gave the 5-thioureido derivative 7 , which on methylation with methyl iodide afforded ethyl 1-(2,3-O-isopropylidene-β-D-ribofuranosyl)-5-[(N'-ethoxycarbonyl-S-methylisothiocarbamoyl)amino]pyrazole-4-carboxylate ( 8 ). Ring closure of 8 under alkaline media furnished 6-amino-1-(2,3-O-isopropylidene-β-D-ribofuranosyl)-1H-pyrazolo[3,4-d]-1,3-oxazin-4-one ( 10 ), which on deisopropylidenation afforded 4 in good yield. 6-Amino-1-(β-D-ribofuranosyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one ( 5 ) has also been synthesized from the AICA riboside congener 5-amino-1-(2,3-O-isopropylidene-β-D-ribofuranosyl)pyrazole-4-carboxamide ( 12 ). Treatment of 12 with benzoyl isothiocyanate, and subsequent methylation of the reaction product with methyl iodide gave 1-(2,3-O-isopropylidene-β-D-ribofuranosyl)-5-[(N'-benzoyl-S-methylisothiocarbamoyl)amino]pyrazole-4-carboxamide ( 15 ). Base mediated cyclization of 15 gave 6-amino-1-(2,3-O-isopropylidene-β-D-ribofuranosyl)-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-one ( 14 ). Deisopropylidenation of 14 with aqueous trifluoroacetic acid afforded 5 in good yield. Compound 4 was devoid of any significant antiviral or antitumor activity in culture.     

Stereoselective synthesis of pyrrolo[2,3-d]pyrimidine α- and β-D-ribonucleosides from anomerically pure D-ribofuranosyl chlorides: Solid-Liquid Phase-Transfer Glycosylation and 15N-NMR Spectra

Solid-liquid phase-transfer glycosylation (KOH, tris[2-(2-methoxyethoxy)ethye]amine ( = TDA-1), MeCN) of pyrrolo[2,3-d]pyrimidines such as 3a and 3b with an equimolar amount of 5-O-[(1,1 -dimethylethyl)dimethylsilyl]-2,3-O-(1-methylethylidene)-α-D -ribofuranosyl chloride (1) [6] gave the protected β-D -nucleosides 4a and 4b , respectively, stereoselectively (Scheme). The β-D -anomer 2 [6] yielded the corresponding α-D -nucleosides 5a and 5b with traces of the β-D -compounds. The 6-substituted 7-deazapurine nucleosides 6a , 7a , and 8 were converted into tubercidin (10) or its α-D -anomer (11) . Spin-lattice relaxation measurements of anomeric ribonucleosides revealed that T₁ values of H? C(8) in the α-D -series are significantly increased compared to H? C(8) in the β-D -series while the opposite is true for T₁ of H? C(1′). ¹⁵N-NMR data of 6-substituted 7-deazapurine D -ribofuranosides were assigned and compared with those of 2′-deoxy compounds. Furthermore, it was shown that 7-deaza-2′deoxyadenosine ( = 2′-deoxytubercidin; 12 ) is protonated at N(1), whereas the protonation site of 7-deaza-2′-deoxyguanosine ( 20 ) is N(3).     

2,4-Disubstituted Pyrrolo[2,3-d]pyrimidine α-D- and β-D-Ribofuranosides Related to 7-Deazaguanosine

Nucleobase-anion glycosylation (KOH, tris[2-(2-methoxyethoxy)ethyl]amine (TDA-1), MeCN) of the pyrrolo[2,3-d]pyrimidines 4a – d with 5-O-[(1,1-dimethylethyl)dimethylsilyl]-2,3-O-(1-methylethylidene)-α-D -ribo-furanosyl chloride ( 5 ) gave the protected β-D -nucleosides 6a – d stereoselectively (Scheme 1). Contrary, the β-D -halogenose 8 yielded the corresponding α-D -nucleosides ( 9a and 9b ) apart from minor amounts of the β-D -anomers. The deprotected nucleosides 10a and 11a were converted into 4-substituted 2-aminopyrrolo[2,3-d]-pyrimidine β-D -ribofuranosides 1 . 10c , 12 , 14 , and 16 and into their α-D -anomers, respectively (Scheme 2). From the reaction of 4b with 5 , the glycosylation product 7 was isolated, containing two nucleobase moieties.     

Synthesis of 5-Methyluridine and Its 5′-Mercapto-, 2-Amino-, and 4′,5′-Unsaturated Analogues

The stereospecific cis-hydroxylation of 1-(2,3-dideoxy-β-D -glyceropent-2-enofuranosyl)thymine (1) into 1-β-D -ribofuranosylthymine (2) by osmium tetroxide is described. Treatment of 2′,3′-O, O-isopropylidene-5-methyl-2,5′-anhydrouridine (8) with hydrogen sulfide or methanolic ammonia afforded 5′-deoxy-2′,3′-O, O-isopropylidene-5′-mercapto-5-methyluridine (9) and 2′,3′-O, O-isopropylidene-5-methyl-isocytidine (10) , respectively. The action of ethanolic potassium hydroxide on 5′-deoxy-5′-iodo-2′,3′-O, O-isopropylidene-5-methyluridine (7) gave rise to the corresponding 1-(5-deoxy-β-D -erythropent-4-enofuranosyl)5-methyluracil (13) and 2-O-ethyl-5-methyluridine (14) . The hydrogenation of 2 and its 2′,3′-O, O-isopropylidene derivative 4 over 5% Rh/Al₂O₃ as catalyst generated diastereoisomers of the corresponding 5-methyl-5,6-dihydrouridine ( 17 and 18 ).     

Synthesis of indazole C-nueleosides and analogues

1-Deoxy-1-diazo-3,6-anhydro-4,5,7-tri-O-benzoyl-D-allo-heptulosc (III) has been prepared from 2,5-anhydro-3,4,6-tri-O-benzoyl-D-allonic acid. 1,3-Dipolar cycloaddition of III to benzyne afforded the indazole C-nucleoside analog V. Cycloaddition of methyl 6-deoxy-6-diazo-2,3-O-isopropylidene-β-D-ribohexofuranosid-5-ulose (IV) to the benzyne generated from 5-methyl-anthranilic acid gave a mixture of the β-isomeric C-glycosylindazoles VI and VII along with traces of the corresponding α-anomers VIa and VIIa. Finally, a multistep transformation of the acyclic carbohydrate moiety of 2,3,4,5-tetra-O-acetyl-1-(indazol-3-yl)-keto-D-ribopentulose (I, R = H, n = 3 , D-ribo) led to the C-nucleoside indazole, 3-(2,3-O-isopropylidene-β-D-ribofuranosyl)-indazol (X), as the major product.     

A New Total Synthesis of D-threo-L-talo-Octose

A new approach to the total, asymmetric synthesis of D -threo-L -talo-octose ((?)- 1 ) and its derivatives is presented. It is based on the chemoselective Wittig-Horner monoolefination of a 5-deoxy-D -ribo-hexodialdose derivative 4 obtained by selective reduction of (?)-5-deoxy-2.3-O-isopropylidene-/β-D -ribo-hexofuranurono-6,1-lactone ((?)- 3 ). Allylic bromination of the resulting methyl (E)-oct-6-enofuranuronate (+)- 5 followed by intramolecular nucleophilic displacement of the so-obtained bromides gave a 13.3:1 mixture of (?)-methyl (E)-l,4-anhydro-6,7-dideoxy-2,3-O-isopropylidene-β-L -talo-oct-6-enopyranuronate ((?)- 8 ) and methyl (E)-l,4-anhydro-6,7-dideoxy-2,3-O-isopropylidene-α-D -allo-oct-6-enopyranuronate ( 9 ). The double hydroxylation of the enoate (?)- 8 followed Kishi's rule and gave the corresponding D -threo-β-L -talo-octopyranuronate derivative (?)- 11 with a good diastereoselectivity. Reduction of ester (?)- 11 and deprotection led to pure (?)- 1 .     

4-Oxa(thia)-9-oxa-2-azabicyclo[4.2.1]nonane-3-on(thion) derivatives

The synthesis of 7,8-dihydroxy-2-(2-methoxycarbonylethyl)-4,9-dioxa-2-azabicyclo[4.2.1]nonane- 3-thione ( 16 ) and of its parents 9-oxa-4-thia-3-thione 17 , and 9-oxa-4-thia-3-one 18 is described. The conversion of 5′-deoxy-5′-iodo-2′,3′-O, O-isopropylidene-5,6-dihydrouridin ( 1 ) into the 2-O-methyl-5,6-dihydrouridine 5 , the 5′-O-acetyl-5,6-dihydrouridine 4 , and into the N-(5-O-acetyl-2,3-O, O-isopropylidene-β-D -ribofuranosyl)-N-(2-methoxycarbonyl thyl)-urea ( 6 ) invoked 2′,3′-O, O-isopropylidene-2,5′-anhydro-5,6-dihydrouridine ( 2 ) as the common intermediate.     

Desoxy-nitrozucker. 13. Mitteilung. Herstellung ungeschützter und partiell geschützter 1-Desoxy-1-nitro-D-aldosen sowie Röntgenstrukturanalysen einiger ihrer Vertreter

Preparation of Unprotected and Partially Protected 1-Deoxy-1-nitro-D -aldoses and Some Representative X-Ray Structure Analyses The unprotected and partially protected 1-deoxy-1-nitro derivatives of α-and β-D -glucopyranose (see 15 and 14 ), β-D -mannopyranose (see 16 ), N-acetyl-β-D -glucosamine (see 17 ), β-D -galactofuranose (see 19 ), β-D -ribofuranose (see 20 ), α-D -arabinofuranose (see 21 ), 4,6-O-benzylidene-β-D -glucose (see 40 ), N-acetyl-4,6-O-benzylidene-β-D -glucosamine (see 41 ), and 4,6-O-benzylidene-β-D -galactose (see 42 ) were prepared by ozonolysis of the corresponding nitrones which were obtained from the acid-catalyzed reaction of p-nitrobenzaldehyde with the hydroxylamine 4 , the unprotected oximes 3 and 5–9 and the 4,6-O-benzylidene oximes 35–37 , respectively (Schemes 1–3). The gluco- and manno-nitrones 10 and 12 were isolated, and their ring size and their anomeric and (E/Z) configurations were determined by NMR spectroscopy and by their transformation into their corresponding nitro derivatives. The structure of the deoxynitroaldoses were determined by NMR spectroscopy, polarimetry, and, in the case of 14 , 16 , and 17 , by formation of the 4,6-O-benzylidene ( 14 → 40 ) or 4,6-O-isopropylidene ( 16 → 43 , 17 → 23 ) derivatives (Scheme 3). Acetylation of the nitroglucopyranose 14 , the 2-acetamido-nitroglucopyranose 17 , and the nitrogalactofuranose 19 gave the crystalline peracetylated nitroaldoses 22 , 24 , and 45 , respectively (Scheme 4, Figs. 1 and 3); acetylation of the nitromannopyranose 16 gave the nitro-arabino-glycal 44 (Scheme 4). The structure of the peracetylated nitroglucopyranose 22 , the nitroglucosamine 25 , the nitrogalactofuranose 45 , and the nitroribofuranose 20 were confirmed by X-ray analysis (Figs. 1 4). In all cases, including the β-D -glucopyranose derivative 22 , considerably shortening of the (endocyclic) C(1)-O bond was observed. Base-catalyzed anomerization of the β-D -configurated nitroglucopyranose 14 , the nitromannopyranose 16 , the benzylidene acetal 40 of nitroglucose, and the 2,3,4,6-tetraacetylated glucosamine derivative 24 gave the corresponding nitro-α-D -aldoses 15 , 26 , 47 , and 25 , respectively (Scheme 4).     

Synthesis of 8-amino-4-methylthio-6-methyl-2-(β-D-ribofuranosyl)-2,6-dihydro-1,2,3,5,6,7-hexaazaacenaphthylene and an unusual reductive ring-opening of the 1,2,3,5,6,7-hexaazaacenaphthylene ring system

The tricyclic nucleoside 8-amino-4-methylthio-6-methyl-2-(β-D-ribofuranosyl)-1,2,3,5,6,7-hexaazaacenaphthylene ( 3 ) was synthesized from 3-cyano-4,6-bis(methylthio)-1-(β-D-ribofuranosyl)pyrazolo[3,4-d]pyrimidine ( 1 ). Attempts to synthesize 8-amino-6-methyl-2-(β-D-ribofuranosyl)-1H-2,6-dihydro-1,2,3,5,6,7-hexaazaacenaphthylene ( 5 ) ([an aza analog of 6-amino-4-methyl-8-(β-D-ribofuranosyl)-1,3,4,5,8-pentaazaacenaphthylene (TCN)], which is a potent antitumor agent), by the treatment of 3 with Raney nickel did not afford the desired aza analog of TCN. Instead, it was established that a reductive cleavage of the pyridazine moiety of 3 had occurred to give 4-methylamino-6-methylthio-1-(β-D-ribofuranosyl)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxamidine ( 6 ). Assuming that solubility was a problem in the reductive step, the isopropylidene derivative of 3 , 8-amino-6-methyl-4-methylthio-2-(2,3-O-isopropylidene-β-D-ribofuranosyl)-2,6-dihydro-1,2,3,5,6,7-hexaazaacenaphthylene ( 8 ), was treated with Raney nickel, only to observe that a similar reductive ring cleavage of 8 had occurred to afford 4-methylamino-6-methylthio-1-(2,3-O-isopropylidene-β-D-ribofuranosyl)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxamidine ( 10 ) and 4-methylamino-1-(2,3-O-isopropylidene-β-D-ribofuranosyl)-1H-pyrazolo[3,4-d]pyrimidine-3-carboxamidine ( 11 ). Structural assignments for all products were established by physico-chemical procedures.     

Synthesis and Biological Evaluation of 2-(2-Deoxy-β-D-ribofuranosyl)pyridine-4-carboxamide

A new protected 2-deoxy-D -ribose derivative, 5-O-[(tert-butyl)diphenylsilyl]-2-deoxy-3,4-O- isopropylidene-aldehydo-D -ribose ( 5 ), was synthesized starting from 2-deoxy-D -ribose. This compound was coupled with 2-lithio-4-(4,5-dihydro-4,4-dimethyloxazol-2-yl)pyridine giving a D /L -glycero-mixture 7 of 5-O-[(tert-butyl)diphenylsilyl]-2-deoxy-1-C-[4-(4,5 -dihydro-4,4-dimethyloxazol-2-yl)pyridin-2-yl]-3,4-O-isopropylidene- D -erythro-pentitol. The mixture 7 was 1-O-mesylated with methanesulfonyl chloride and subsequently treated with CF₃COOH/H₂O and ammonia to afford the α/β-D -anomers 10 of 2-(2-deoxy-D -ribofuranosyl)pyridine-4-carboxamide. Both anomers were purified and separated by HPLC and identified by NMR and DCI-MS. Anomer β-D - 10 was evaluated against a series of tumor-cell lines and a variety of viral strains. No antitumor or antiviral activity was observed.     

Die Herzglykoside des Pfeilgiftes von Lophopetalum toxicum LOHER. 13. Mitteilung über Celastraceen-Inhaltsstoffe

The Heart Glycosides of the Arrow Poison of Lophopetalum toxicum LOHER From the cytotoxic and positive inotropic acting bark extract of the Philippinan Lophopetalum toxicum eight heart glycosides have been isolated and their structures have been elucidated mainly by field-desorption-MS- and ¹- and ¹³C-NMR spectroscopy. Besides the known k-Strophanthidin ( 1 ), Antiarigenin ( 6 ) and β-Antiarin (Antiarigenin-3-β-O-α-L -rhamnoside, 10 ) the following mono- and diglycosides could be identified: strophanthidin-3-β-O-α-6-desoxy-D -allopyranoside (strophalloside, 2 ), strophanthidin-3-β-O-β-6-desoxy-D -glucopyranoside (= Strophanthidin chinovoside, 3 ), strophanthidin-3-β-O[-4Oβ-D -allopyranosyl-β-6-desoxy-D -allopyranoside] ( 4 ), strophanthidin-3-β-O-[3-O-β-D -glucopyranosyl-β-6-desoxy-D -talopyranoside] ( 5 ), antiarigenin-3-β-O-[3-O-β-D -gulopyranosyl-β-6-desoxy-D -talopyranoside] ( 7 ), antiarigenin-3-β-O-[4O-β-D -allopyranosyl-β-6-desoxy-D -allopyranoside] ( 8 ), and antiarigenin-3-β-O-β-6-desoxy-D -allopyranoside (antiallosid) ( 9 ). The structure of strophanthidinchinovoside ( 3 ) could be confirmed by synthesis.     

Molluscicidal Saponins from Talinum tenuissimum DINTER

Two new saponins, β-D -glucopyranosyl 3-O[O-βD -xylopyranosyl-(1→3)-O-(β-D -glucopyranosyluronic acid)]oleanolate ( 1 ) and 3-O-[O-β-D -xylopyranosyl-(1→3)-O-(β-D-glucopyranosyluronic acid)]oleanolic acid ( 2 ), have been isolated from the tubers of Talinum tenuissimum. The structures have been established mainly by ¹³C-NMR and FAB-MS. The monodesmosidic saponin 2 exhibits very strong molluscicidal activity against the schistosomiasis-transmitting snail Biomphalaria glabrata.     

Expeditious Synthesis of a Trisubstrate Analogue for α(1→3)Fucosyltransferase

Abstract

The synthesis of cyclohexyl 2-acetamido-2-deoxy-3-O-{2-O-[2-(guanosine 5′-O-phosphate)ethyl]-α-L-fucopyranosyl}-β-D-glucopyranoside (1), a potential inhibitor of α(1→3)fucosyltransferases, is described. Target compound 1 was assembled via fucosylation of cyclohexyl 2-acetamido-2-deoxy-4,6-O-isopropylidene-β-D-glucopyranoside (6) with ethyl 2-O-[2-(benzoylhydroxy)ethyl]-3,4-O-isopropylidene-1-thio-β-L-fucopyranoside (5) followed by debenzoylation, subsequent condensation of the resulting compound with 3′,4′ -di-O-benzoyl-5′ -O-(2-cyanoethyl-N,N-diisopropylphosphoramidite)-2-N-diphenylacetylguanosine (10) and deprotection.     

<Superscript>1</Superscript>H NMR study on intramolecular hydrogen bonding in 2,3-<Emphasis Type="Italic">O</Emphasis>-isopropylidene-D-ribofuranosides and their 5(4)-hydroxy derivatives

¹H NMR study showed the possibility for intramolecular hydrogen bonding in 5(4)-hydroxy derivatives of 2,3-O-isopropylidene-β-D-ribofuranose in CDCl₃. The obtained data were used to interpret differences in the ¹H NMR spectra of structurally related 5-halo-2,3-O-isopropylidene-D-ribofuranosides and four newly synthesized diastereoisomeric 5-bromo-5-deoxy-4-hydroxy-2,3-O-isopropylidene-D-ribofuranosides.     

Selectively Deoxygenated Derivatives of β-Maltosyl-(1→4)-Trehalose as Biological Probes

ABSTRACT

The four derivatives of β-maltosyl-(1→4)-trehalose have been synthesized, which are monodeoxygenated at the site of one of the primary hydroxyl groups. The tetrasaccharides were constructed in [2+2] block syntheses. Thus, 6′″-deoxy-β-maltosyl-(1→4)-trehalose was prepared by selective iodination of allyl 2,3,6,2′,3′-penta-O-acetyl-β-maltoside (3) followed by catalytic hydrogenolysis and coupling with 2,3-di-O-benzyl-4,6-O-benzylidene-α-D-glucopyranosyl 2′,3′,6′-tri-O-benzyl-α-D-glucopyranoside (9), and 6″-deoxy-β-maltosyl-(1→4)-trehalose by selective iodination of allyl 4′,6′-O-isopropylidene-β-maltoside (14), coupling with 9, and one-step hydrogenolysis at the tetrasaccharide level. For the synthesis of 6′-deoxy-β-maltosyl-(1→4)-trehalose, the diol 2,3-di-O-benzyl-4,6-O-benzylidene-α-D-glucopyranosyl 2′,3′-di-O-benzyl-α-D-glucopyranoside (22) was selectively iodinated and glycosylated with acetobromomaltose followed by catalytic hydrogenolysis. The 6-deoxy-β-maltosyl-(1→4)-trehalose was obtained upon selective iodination of a tetrasaccharide diol.     

arabinonucleosides

The α-D-arabinonucleosides of cytosine ( 6 ) and 5-fluorouracil ( 9 ) were prepared from the 2,3,-5-tri-O-benzoyl-D-arabinofuranosyl halides, in keeping with the trans rule. The 2′-O-methyl-)3-D-arabinonucleosides of 5-fluorouraeil (β- 14 ) and adenine (β- 21a ) were prepared from 3,5-di-O-(4-ehlorobenzoyl)-2-O-methyl-α-D-arabinofuranosyl chloride, although in both cases a lesser amount of the α-anomer was also found. Reaction of 3,5-di-O-(4-chlorobenzoyl)-2-deoxy-2-(methylthio)-α-D-arabinofuranosyl chloride, prepared in four steps from methyl 2,3-anhydro-α-D-ribofurano-side ( 15 ), with N-benzoyladenine gave slightly more of the β- than the α-arabinonucleoside 20b . The β-anomer was converted to 9-[2-deoxy-2-(methylthio)-β-D-arabinofuranosyl]adenine. Only 1-α-D-arabinofuranosylcytosine ( 6 ) proved to be cytotoxic.     

Two new triterpenoids from the seeds of blackberry (Rubus fructicosus)

Two new ursane-type triterpenoids (1, 2) attached to isopropylidenedioxy group were isolated from the seeds of blackberry (Rubus fructicosus L., Rosaceae) along with two known ursane-type triterpenoids, 2,3-O-isopropylidenyl-2α,3α,19α-trihydroxyurs-12-en-28-oic acid (3) and 1β-hydroxyeuscaphic acid (4). The chemical structures of 1 and 2 were determined to be 2,3-O-isopropylidene-1β,2β,3β,19α-tetrahydroxyurs-12-en-28-oic acid and 1,2-O-isopropylidene-1β,2α,3α,19α-tetrahydroxyurs-12-en-28-oic acid, respectively, based on spectroscopic data. Additionally, their cytotoxic activity towards HL-60 human leukaemia cells was evaluated. Among them, 3 demonstrated a clear cytotoxic activity with 72.8 μM of IC₅₀ value.