Study on the Ring-opening of α-L-arabinopyranoside Benzylidene Acetals

OSW-1 was isolated from the bulbs of Ornithogalum saundersiae by Satoshi Kubo of Japan in 1992,which is 100 times more potent than other anticancer agents available in clinical use,such as CTP and TAX. The oligosaccharides of OSW-1 is composed of 2-O-acetyl-α-L-arabinopyranoside and 2-O-4-methoxybenzoyl-β-D-xylopyranosyl by 1-3. We study on the Synthesis of the oligosaccharides of OSW-1. Now we suggest the possible pathway of 2-O-acetyl-α-L-arabinopyranoside, especially study on the ring-opening of its benzylidene acetals.     

Analysis of antitumor active OSW-1 and its analogues by liquid chromatography coupled with electrospray and atmospheric pressure chemical ionization quadrupole mass spectrometry

Three cholestane glycosides including OSW-1 with antitumor activity and two new analogues with modified steroidal side chains, thienyl OSW-1 and silylated thienyl OSW-1, were synthesized. Analyses were performed using optimized, reversed-phase liquid chromatography (LC) with electrospray ionization and atmospheric pressure chemical ionization quadrupole mass spectrometry (MS). The ionization mode and polarity, cone voltage, and chromatographic conditions were evaluated. The optimum LC/MS conditions to obtain valuable ions, indispensable for identifying the structures, are described. The key fragmentation pathways, which will be useful for confirming the detailed structures of steroidal glycosides, are also proposed.     

DNA: 23-Oxa-OSW-1生物靶标?

虎眼万年青皂苷OSW-1来源于百合科植物虎眼万年青, 是一种具有良好抗肿瘤活性的皂苷成分. 其类似物23-Oxa-OSW-1具有OSW-1一样潜在的活性, 对恶性肿瘤细胞具有很强的抑制作用, IC50为0.052～0.4 μmol•L－1. 但OSW-1的生物靶标还没有报道. 利用一维和二维 1H NMR技术首次发现23-Oxa-OSW-1与DNA间有很强的相互作用. NMR数据分析表明23-Oxa-OSW-1中木糖部分可能参与了与DNA的结合.     

New disaccharide blocks for OSW-1 and its analogs

A new disaccharide block for OSW-1 natural steroidal antitumor agent was described. Regioisomeric 2- and 3-O-p-methoxybenzoyl derivatives of phenyl 1-thio-??-d-xylopyranoside and phenyl 2-O-acetyl-1-thio-??-l-arabinopyranoside derivatives blocked at positions 3 and 4 by R₃Si groups were synthesized with a view to use them in the preparation of OSW-1 analogs modified at the disaccharide fragment.     

Practical synthesis of 16,22-diketocholesterol acetate, a precursor of anticancer saponin OSW-1, from diosgenin

An improved method using dibromide protection of the 5,6-double bond has been developed for the synthesis of the title compound, which is a key intermediate in the synthesis of saponin OSW-1 from diosgenin.     

A new strategy for synthesizing the steroids with side chains from steroidal sapogenins: synthesis of the aglycone of OSW-1 by using the intact skeleton of diosgenin

The protected aglycone of saponin OSW-1, a new antitumor natural product, was synthesized in 13 linear steps in 9.5% overall yield by utilizing the intact skeleton of diosgenin. This strategy demonstrated a higher efficiency than the routine synthesis of steroids with side chains.     

Three-dimensional structures of OSW-1 and its congener

The 3D structures of an antitumor glycosylsterol OSW-1 and its closely related congener were investigated by NMR studies and an X-ray crystallographic analysis. The disaccharide moiety was found as a structural scaffold for the formation of a hydrophobic cluster by the biologically required functionalities.     

Disaccharide blocks for analogs of OSW-1

The acetalization of phenyl 1-thio-α-L-arabinopyranoside with 2,3-butanedione in the medium of MeOH-CH(OMe)₃-CSA proceeded with the prevailing formation of the corresponding 3,4-bisacetal that further was converted in compounds, which were regio- and stereoisomers of disaccharide block of OSW-1.     

A total synthesis of OSW-1

A new and practical method was developed to synthesize OSW-1, a natural saponin with potent antitumor activities, from (+)-dehydroisoandrosterone, l-arabinose, and D-xylose on gram scale. The synthesis was achieved in 10 linear steps with an overall yield of 6.4% starting from (+)-dehydroisoandrosterone.     

Synthesis of 5(6)-dihydro-OSW-1 by using the intact skeleton of tigogenin

5(6)-Dihydro-OSW-1 (1), an analogue of OSW-1 with the potent anticancer activity, was synthesized by utilizing the intact skeleton of tigogenin in 13 steps in 9.0% overall yield. This synthesis demonstrated an effective and reasonable synthetic strategy for bioactive steroids with side chains as compared with their routine synthesis.     

Synthesis of vespertilin conjugates with OSW-1 disaccharide blocks

The reaction of vespertilin with 2-O-acetyl-3,4-bis-O-(triethylsilyl)-α-l-arabinopyranosyl trichloroacetimidate gave the corresponding glycoside. Removal of the silyl protecting group from the latter and glycosylation of the resulting diol with trichloroacetimidate derived from D-xylose afforded 3,4-regioisomeric glycosides containing OSW-1 disaccharide blocks.     

A highly efficient synthesis of 22-deoxy-OSW-1 by utilizing the intact skeleton of diosgenin

22-Deoxy-OSW-1 (1), an analogue of OSW-1 with the potent anticancer activity, was synthesized by utilizing the intact skeleton of diosgenin in 11 steps in 13.7% overall yield. This synthesis demonstrated an effective and reasonable synthetic strategy for bioactive steroids with side chains.     

A new synthesis of potent antitumor saponin OSW-1 via Wittig rearrangement

OSW-1 and its analogues in which thiophene ring was introduced at the side chain were synthesized employing Wittig rearrangement of 17E(20)-ethylidene-16α-(4′-methyl-2′-thienyl)methyloxy steroid. The synthesis required nine steps from the known 17E(20)-ethylidene-16α-hydroxy steroid in 15.6% overall yield.     

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. In particular, the present route was found convenient for the synthesis of OSW saponin analogues with a C22-ester side chain. Thus, the 23-oxa-analogue of OSW-1 (40) was prepared starting from the industrial dehydroisoandrosterone (1) in a linear eight-step sequence and in 26% overall yield. Analogues with a variety of modified side chains were prepared, via aldol condensation with propionates of varying length, thiopropionate, and acetate (for preparation of 68-75) or via aminolysis of the 22,16-lactone 26 (for preparation of the 23-N-analogues). Cross metathesis (CM) reaction was also found feasible for modification at the final stage from C22-allyl ester 70. Valuable structure-activity relationships (SAR), together with the practical synthetic approach, have thus been provided to set a new stage for further studies on this new type of antitumor structures.     

Total synthesis of the anticancer natural product OSW-1

The highly potent anticancer natural saponin OSW-1 has been successfully synthesized from commercially available 5-androsten-3beta-ol-17-one 79 in 10 operations with 28% overall yield. The key steps in the total synthesis included a highly regio- and stereoselective selenium dioxide-mediated allylic oxidation of 80 and a highly stereoselective 1,4-addition of alpha-alkoxy vinyl cuprates 68 to steroid 17(20)-en-16-one 12E to introduce the steroid side chain. This total synthesis demonstrated once again the versatile synthetic applications of alpha-halo vinyl ether chemistry developed in our laboratories.     

Stereoselective approach to potential scaffold of A-nor B-aromatic OSW-1 analogues via [4+2] cycloaddition of o-quinodimethane

A-nor B-aromatic steroidal skeleton was efficiently constructed by means of o-quinodimethane chemistry with exclusive stereoselectivity. The benzocyclobutene substrate for generation of the o-quinodimethane intermediate and subsequent [4+2] cycloaddition could be synthesized via (E)-selective Julia–Kocienski olefination and diastereoselective Grignard addition reactions. The synthesized tricyclic steroid-like compound with a trans-diol substructure would be utilized for divergent syntheses of potentially antitumor OSW-1 analogues with the truncated steroidal aglycone.     

Synthesis of pennogenin utilizing the intact skeleton of diosgenin

Pennogenin (1) is an aglycone of bioactive com-ponents of Chinese traditional medicine named Chonglou(Paris),[1] which belongs to C-17-hy- droxyl-steroidal sapogenin. It is well known that Chonglou as well as the related herbs containing pennogenin and its glycosides have been used as haemostatic agents in clinic. They also exhibit antibi-otic and antitumor activity[1,2]. With the demand amount of Chonglou as well as the related drugs increasing while the plant resource decreasing day by day…     

New Strategy for Synthesis of the Disaccharide Moiety of the Highly Potent Anticancer Natural Product OSW-1

The facile synthesis of a partially protected OSW-1 disaccharide moiety, having a 2-O-p-methoxybenzoyl-β-D-xylopyranosyl-(1 → 3)-2-O-acetyl-L-arabinopyranoside structure, was elaborated by glycosylation in a β-stereoselective fashion. The xylopyranose donors were synthesized by a short synthetic approach via convenient selective 1,2-diacetal protection of 3,4-trans-diequatorial hydroxyl group. Regioselective ring opening of 1,2-diacetal-protected substrates efficiently led to the arabinopyranose acceptor with a free 3-hydroxyl group. Glycosylation of the xylopyranose donor with the arabinopyranose acceptor provided the β-disaccharide.     

Li~3Al的几何结构和垂直激发态光谱的量子化学研究

在ab initio DZP水平上, 用能量梯度法对Li~3Al的三种几何构型进行了优化, 并对其中两个能量较低的构型用单、双激发组态相互作用(CISD)进行了垂直跃迁能和振子强度计算, 结果表明: Li~3Al(C~2~v)中存在着三个强度较大的跃迁, 分别是从基态跃迁到1^1B~1, 2^1B~1, 5^1A~1态。Li~3Al(D~3~h)中存在着四个强度较大的跃迁, 分别是从基态跃迁到1^1B~2, 2^1A~1, 3^1B~2, 3^1A~1态。这些强度较大的跃迁均为粒子穴跃迁。     

红外光谱酰胺Ⅲ带用于蛋白质二级结构的测定研究

用甲醇对BSA和RaseA等蛋白质进行变性处理,结合蛋白质酰胺带的拟合结果对酰胺带各二级结构的谱峰进行了初步指认:1330～1290cm^-1为α-螺旋;1295～1265cm^-1为β-转角;1270～1245cm^-1为无规卷曲;1250～1220cm^-1为β-折叠.依据这些谱峰归属,对一些已知二级结构的蛋白质进行了测定,所得结果与X射线衍射数据以及酰胺带的定量结果基本一致.