Synthesis of the A,B-ring-truncated OSW saponin analogs and their antitumor activities.

The A,B-ring-truncated OSW saponin analogs (1, 18a, and 18b) were synthesized. These greatly simplified trans-hydrindane disaccharides retained considerable inhibitory activity against the growth of HeLa and Jurkat T cells (IC(50)=0.8-21.

Antibacterial diterpenoids from Sagittaria pygmaea.

There were five new diterpenoids, 18-beta-D-3',4'-diacetoxyxylopyranosyl-ent-kaur-16-ene (1), 18-beta-L-3',5'-diacetoxyarabinofuranosyl-ent-kaur-16-ene (2), 18-beta-D-3',6'-diacetoxyglucopyranosyl-ent-kaur-16-ene (3), ent-isopimar-8(14),15-dien-19-oic acid (4), and 5alpha-hydroxy-ent-rosa-15-en-18-oic acid (5), isolated from the whole herb of Sagittaria pygmaea. Their structures and relative configurations were established based on spectroscopic studies, chemical methods, and X-ray crystallographic analysis. Compound 2 exhibited significant antibacterial activity against the oral pathogens, Streptococcus mutans ATCC 25 175 and Actinomyces viscosus ATCC 27 044, with MIC values against both pathogens of 15.

Exploration of the correlation between the structure, hemolytic activity, and cytotoxicity of steroid saponins.

The hemolytic activity of a collection of 63 steroid saponins was determined. The correlations between these structures and their hemolytic and cytotoxic activities are discussed. It has been demonstrated that the hemolytic activity of steroid saponins is highly dependent on their structures, that is, the sugar length, the sugar linkage, the substitutes on the sugar, as well as the aglycone.

Synthesis of OSW saponin analogs with modified sugar residues and their antiproliferative activities.

Eight monosaccharide analogs of the potent antitumor OSW saponins (2-9) were synthesized. One analog, 2-O-acetyl-alpha-l-arabinopyranoside 3, showed antiproliferative activity against the Jurkat cells (IC(50)=0.078microM) comparable to that of the disaccharide derivative (1).

Aryl C-glycosylation of phenols with glycosyl trifluoroacetimidates.

Aryl C-glycosylation of a variety of phenols with glycosyl trifluoroacetimidates in the presence of TMSOTf was examined, leading to the corresponding ortho-hydroxyaryl C-glycosides in variable yields.

Synthesis and cytotoxicities of dioscin derivatives with decorated chacotriosyl residues.

Two series of dioscin derivatives (4a-o and 5a-o) with selected modifications at the 6' and 4''' positions of the chacotriosyl residue, respectively, were synthesized. All the 6'-N-acyl-dioscin derivatives did not show considerable inhibitory activities at 10 microM, while most of the 4'''-O-(2-N-acyl)ethyl-dioscin derivatives behaved as potent as dioscin, against the growth of tumor cells.

Facile conversion of spirostan saponin into furostan saponin: synthesis of methyl protodioscin and its 26-thio-analogue.

[reaction: see text] A facile approach for the conversion of a spirostan saponin into its furostan counterpart, as illustrated by the transformation of dioscin to methyl protodioscin (and its 26-thio-analogue), has been developed.

Synthesis of 3-O-(beta-D-xylopyranosyl-(1-->2)-beta-D-glucopyranosyl)-3'-O-(beta-D-glucopyranosyl)tamarixetin, the putative structure of aescuflavoside A from the seeds of Aesculus chinensis.

3-O-(beta-D-xylopyranosyl-(1-->2)-beta-D-glucopyranosyl)-3'-O-(beta-D-glucopyranosyl)tamarixetin, the putative flavonal glycoside named aescuflavoside A, isolated from the seeds of Aesculus chinensis, is synthesized via regioselective glycosylation of 7-O-benzyltamarixetin with glycosyl bromides under phase-transfer-catalyzed conditions.

Toward synthesis of the regular sequence of heparin: synthesis of two tetrasaccharide precursors.

Two fully protected tetrasaccharides, which represent precursors for the synthesis of the regular sequence of heparin, were synthesized via coupling of a pair of disaccharide trichloroacetimidates with a thioglycoside and a glucosamine derivative, respectively, in a sequential manner.

OSW saponins: facile synthesis toward a new type of structures with potent antitumor activities.

[reaction: see text] OSW saponins, featuring a 16beta,17alpha-dihydroxycholest-22-one aglycon and an acylated beta-D-xylopyranosyl-(1-->3)-alpha-L-arabinopyranosyl residue attached to the 16-hydroxyl group, have recently been discovered from a group of lily plants, which show potent antitumor activities with a novel mechanism of action. This paper describes an aldol approach to the stereoselective construction of the 16alpha,17alpha-dihydroxycholest-22-one structure from 16alpha-hydroxy-5-androsten-17-ones and propionates. Elaboration of the aldol adducts toward OSW-1, involving installation of the isoamyl ketone side chain, inversion of the 16-hydroxyl configuration, and selective protection of the C22-oxy function, has been explored and accomplished.

Effects of polyphyllin D, a steroidal saponin in Paris polyphylla, in growth inhibition of human breast cancer cells and in xenograft.

Paris polyphylla is a traditional Chinese Medical herb that has been used in treating cancer for thousands of year. Without studies on the anticancer effects of Paris polyphylla being initiated before, we have first studied the component of Paris polyphylla and have spotted out a steroidal saponin, polyphyllin D. As long as the chemical structure and the improved synthesis of polyphyllin D were ascertained, both in vitro to in vivo studies were performed.

Total synthesis of CRM646-A and -B, two fungal glucuronides with potent heparinase inhibition activities.

[reaction: see text] CRM646-A (1) and -B (2), two fungal glucuronides with a dimeric 2,4-dihydroxy-6-alkylbenzoic acid (orcinol p-depside) aglycone showing significant heparinase and telomerase inhibition activities, were synthesized for the first time. The successful approach involved construction of the phenol glucuronidic linkage, via coupling of the orsellinate derivative 27 with glucuronate bromide 7, before assembly of the phenolic ester linkage in the depside aglycone. Attempts via direct glycosylation of the depside aglycone derivatives were not successful.

Three dammarane-type saponins from Gynostemma pentaphyllum.

Three new dammarane-type saponins, compounds 1 - 3, were isolated from the aerial parts of Gynostemma pentaphyllum. Their structures were determined using NMR analysis and acid hydrolysis. The structure and stereochemistry of compound 1 were confirmed by X-ray crystallography.

Apoptosis induced by a new member of saponin family is mediated through caspase-8-dependent cleavage of Bcl-2.

OSW-1 is a new member of cholestane saponin family, which is cytotoxic against several types of malignant cells. We reported herein that OSW-1 induced apoptosis of mammalian cells in a concentration- and time-dependent manner. The drug-induced apoptosis was mediated through the mitochondrial pathway, involving the cleavage of Bcl-2.

Triterpenoids from Sanguisorba officinalis.

Seven triterpenoids, i.e., 3beta-[(alpha-L-arabinopyranosyl)oxy]-19beta-hydroxyurs-12,20(30)-dien-28-oic acid (1), 3beta-[(alpha-L-arabinopyranosyl)oxy]-urs-11,13(18)-dien-28-oic acid beta-D-glucopyranosyl ester (2), 2alpha,3alpha,23-trihydroxyurs-12-en-24,28-dioic acid 28-beta-D-glucopyranosyl ester (3), 3beta-[(alpha-L-arabinopyranosyl)oxy]-urs-12,19(20)-dien-28-oic acid (4), 3beta-[(alpha-L-arabinopyranosyl)oxy]-urs-12,19(29)-dien-28-oic acid (5), 3beta-[(alpha-L-arabinopyranosyl)oxy]-19alpha-hydroxyolean-12-en-28-oic acid (6), 2alpha,3beta-dihydroxy-28-norurs-12,17,19(20),21-tetraen-23-oic cid (7), together with three known ones (8-10), were isolated from the roots of Sanguisorba officinalis.

Synthesis of tamarixetin and isorhamnetin 3-O-neohesperidoside.

Two isomeric flavonol 3-O-glycosides, tamarixetin and isorhamnetin 3-O-neohesperidoside (1 and 2), were synthesized. The natural product from Costus spicatus assigned as the former compound is revised to the latter structure.

Kinetic analysis of an efficient DNA-dependent TNA polymerase.

alpha-l-Threofuranosyl nucleoside triphosphates (tNTPs) are tetrafuranose nucleoside derivatives and potential progenitors of present-day beta-d-2'-deoxyribofuranosyl nucleoside triphosphates (dNTPs). Therminator DNA polymerase, a variant of the 9 degrees N DNA polymerase, is an efficient DNA-directed threosyl nucleic acid (TNA) polymerase. Here we report a detailed kinetic comparison of Therminator-catalyzed TNA and DNA syntheses.

Syntheses of chlorogenin 6alpha-O-acyl-3-O-beta-chacotriosides and their antitumor activities.

Chlorogenin 3-O-beta-chacotrioside (1) and its 6alpha-O-acyl derivatives (2-6) were concisely synthesized. Introduction of a hydroxyl or acyloxy group onto the C-6 of the steroidal aglycone of dioscin decreased significantly the cytotoxicity of the parent saponin (dioscin).

Synthesis of anemoclemoside B, the first natural product with an open-chain cyclic acetal glycosidic linkage.

Anemoclemoside B (1), the first natural product containing a brand-new glycosidic linkage, the open-chain cyclic acetal linkage, was synthesized.

Synthesis of alpha-L-threofuranosyl nucleoside triphosphates (tNTPs).

[structure: see text] The alpha-l-threofuranosyl nucleoside triphosphates of T, G, and D (tTTP, tGTP, and tDTP) were synthesized from the described 2'-O-DMT-protected derivatives using the Eckstein method, while the corresponding C derivative (tCTP) was prepared from the 2'-O-acetyl derivative. The prepared alpha-l-threofuranosyl nucleoside triphosphates, despite being one carbon shorter than the native 2'-deoxyfuranosyl nucleoside triphosphates, are effective substrates for selected DNA polymerases.

An in vitro selection system for TNA.

(3'-2')-alpha-l-Threose nucleic acid (TNA) is an unnatural polymer that possesses the rare ability to base-pair with RNA, DNA, and itself. This feature, coupled with its chemical simplicity, makes TNA of interest as a possible progenitor of RNA during the early history of life. To evaluate the functional potential of TNA, we have developed a system for the in vitro selection of TNA.

Polyphyllin D is a potent apoptosis inducer in drug-resistant HepG2 cells.

In a search for new anticancer agents, we identified a novel compound polyphyllin D (PD) (diosgenyl alpha-L-rhamnopyranosyl-(1-->2)-(alpha-L-arabinofuranosyl)-(1-->4)]-[beta-D-glucopyranoside) that induced DNA fragmentation and phosphatidyl-serine (PS) externalization in a hepatocellular carcinoma cell line HepG2 derivative with drug resistance (R-HepG2). PD is a saponin originally found in a tradition Chinese medicinal herb Paris polyphylla. It has been used to treat liver cancer in China for many years.

Multiple-stage tandem mass spectrometry for differentiation of isomeric saponins.

Four isomers of steroidal saponins were differentiated using multiple-stage tandem mass spectrometry combined with electrospray ionization (ESI-MS(n)). With the addition of lithium salt, the [M+Li](+) ions of saponins were observed in the ESI spectra. MS(n) spectra of these [M+Li](+) ions provided detailed structural information and allowed differentiation of the four isomeric saponins.