Oldhamiphylline A: a novel hexacyclic alkaloid from Daphniphyllum oldhami

A novel Daphniphyllum alkaloid, oldhamiphylline A (1), together with five known alkaloids, deoxycalyciphylline B, deoxyisocalyciphylline B, calyciphylline, secodaphniphylline, and calycicine A, was isolated from the leaves of Daphniphyllum oldhami. The structure of 1 was established by spectroscopic methods, especially 2D NMR techniques (1H,1H-COSY, HMQC, HMBC, and NOESY).     

Iseluxine: a novel isoquinolinone alkaloid from Iseia luxurians

A novel isoquinolinone alkaloid, iseluxine (1), has been isolated from the epigeal parts of Iseia luxurians (MORIC.) O'DONELL (Convolvulaceae), a climber indigenous to the tropical Americas. Structural elucidation was achieved by HRMS, 1H NMR, 13C NMR, and HMBC spectroscopy. N- and/or O-methyl derivatives of 1 are already known from certain Magnoliidae families, e.g., the Fumariaceae, the Lauraceae, or the Papaveraceae. Iseluxine, the "missing link" in the biosynthesis of these methyl derivatives from dopamine, is the first isoquinolinone alkaloid characterized by a catechol substructure.     

IP6: A novel anti-cancer agent

Inositol hcxaphosphate (InsP₆ or IP₆) is ubiquitous. At 10 μM to 1 mM concentrations, IP₆ and its lower phosphorylated forms (IP_1–5) as well as inositol (Ins) are contained in most mammalian cells, wherein they are important in regulating vital cellular functions such as signal transduction, cell proliferation and differentiation. A striking anti-cancer action of IP₆ has been demonstrated both in vivo and in vitro, which is based on the hypotheses that exogenously administered IP₆ may be internalized, dephosphorylated to IP_1–5, and inhibit cell growth. There is additional evidence that Ins alone may further enhance the anti-cancer effect of IP₆. Besides decreasing cellular proliferation, IP₆ also causes differentiation of malignant cells often resulting in a reversion to normal phenotype. These data strongly point towards the involvement of signal transduction pathways, cell cycle regulatory genes, differentiation genes, oncogenes and perhaps, tumor suppressor genes in bringing about the observed anti-neoplastic action of IP₆.     

A 6-substituted-5,6-dihydro-2-pyrone from Cryptocarya strictifolia

The structure and absolute configuration of an alpha-pyrone isolated from Cryptocarya strictifolia was elucidated as 6R-(4'R,6'R-dihydroxy-8'-phenyloct-1'-enyl)-5,6-dihydro-2H-pyran-2 -one. Pinocembrin and lysicamine were also isolated.     

6-Hydroxy- and 6-methoxy-beta-carbolines as acetyl- and butyrylcholinesterase inhibitors

In the course of studies directed toward the discovery of novel acetyl- and butyrylcholinesterase (AChE and BChE) inhibitors for the treatment of Alzheimer's disease, we focused on beta-carbolines (BCs). 6-Oxygenated beta-carboline and beta-carbolinium derivatives based on the serotonin template were synthesized and tested in vitro for their ability to inhibit AChE and BChE, respectively. Particularly the carbolinium salts, which can be formed by intracerebral methylation out of the tertiary-BC prodrugs, show inhibitory activity levels reaching those of galantamine, physostigmine, and rivastigmine.     

A novel monoterpenoid indole alkaloid with anticancer activity from Melodinus khasianus

A novel monoterpenoid indole alkaloid with unprecedented 6/5/6/4/6 fused rings, khasuanine A (1), was isolated from the roots of Melodinus khasianus. The structure was determined by extensive analysis of its HR-MS, 1D-, and 2D-NMR spectra. Khasuanine A markedly inhibited the proliferation of PC3 cell with IC₅₀ value of 0.45 μM. Further study showed that khasuanine A was able to induce the apoptosis of PC3 cells by activation of caspase 3 and p53, and by inhibition of Bcl-2.     

A new 6-C-alkylation from an alkyl mannofuranoside 5,6-cyclic sulfate

Methyl 6-C-alkyl-6-deoxy-alpha-D-mannofuranoside derivatives have been synthesized from methyl 2,3-O-isopropylidene-5,6-O-sulfuryl-alpha-D-mannofuranoside (1). In a Path A, reaction of the 5,6-cyclic sulfate 1 with 2-lithio-1,3-dithiane afforded 2-(methyl 6-deoxy-2,3-O-isopropylidene-alpha-D-mannofuranosid-6-yl)-1,3-dith iane (2). Treatment of 2 with n-butyllithium then alkyl iodide gave the corresponding 2-(methyl 5-O-alkyl-6-deoxy-2,3-O-isopropylidene-alpha-D-mannofuranosid-6-yl )-1,3- dithiane. Reaction of 2 with n-butyllithium and 5,6-cyclic sulfate 1 furnished 2-[methyl 6-deoxy-2,3-O-isopropylidene-5-O-(methyl 6-deoxy-2,3-O-isopropylidene-alpha-D-manno-furanosid-6-yl)-alpha-D - mannofuranosid-6-yl]-1,3-dithiane. 2-(Methyl 6-deoxy-2,3-O-isopropylidene-5-O-methyl-alpha-D-mannofuranosid- 6-yl)-1,3-dithiane was converted into the lithiated anion, which after treatment with alkyl halide afforded the corresponding 2-alkyl-C-(methyl 6-deoxy-2,3-O-isopropylidene-5-O-methyl-alpha-D-mannofuranosid-6-y l)-1,3- dithiane. In a Path B, 5,6-cyclic sulfate 1 reacted with 2-alkyl-2-lithio-1,3-dithiane derivatives, which led after acidic hydrolysis to 2-alkyl-2-(methyl 6-deoxy-2,3-O-isopropylidene-alpha-D-mannofuranosid-6-yl)-1,3-dith iane accompanied by methyl 6-deoxy-2,3-O-isopropylidene-alpha-D-lyxo-hexofuranos-5-u loside as the by-product. This methodology was applied to synthesize 2-(methyl 6-deoxy-2,3-O-isopropylidene-5-O-methyl-alpha-D-mannofuranosid-6-y l)-2- (methyl 6-deoxy-2,3-O-isopropylidene-alpha-D-mannofuranosid-6-yl)-1,3-dith iane.     

A novel alkaloid, aristopyridinone A and anti-inflammatory phenanthrenes isolated from Aristolochia manshuriensis

A novel alkaloid, aristopyridinone A (1) and a new phenanthrene, aristolamide II (2), were isolated from Aristolochia manshuriensis (Guanmutong) together with eight known phenanthrenes (3-10). All structures were elucidated by spectroscopic methods. Compound 2 showed a selective inhibitory effect on elastase release by human neutrophils in response to fMLP with an IC₅₀ value of 4.11 μg/mL. Compound 7 exhibited significant inhibitory effects on superoxide anion generation and elastase release with IC₅₀ values of 0.12 and 0.20 μg/mL, respectively.     

Synthesis of 6-deoxy-L-idose and L-acovenose from 1,2: 5,6-di-O-isopropylidene-alpha-D-glucofuranose

A practical route toward the synthesis of 6-deoxy-L-idose and L-acovenose from 1,2:5,6-di-O-isopropylidene-alpha-D-glucofuranose is described. Key steps include the stereoselective hydrogenation of 6-deoxy-1,2:3,5-di-O-isopropylidene-alpha-D-xylo-hex-5-enofuranose, regioselective protection of 6-deoxy-1,2-O-isopropylidene-beta-L-idofuranose at 0-5, and epimerisation of 6-deoxy-5-O-tert-butyldimethylsilyl-1,2-O-isopropylidene-beta-L-idofuranose at C-3.     

6-羟基-3-琥珀酰吡啶单加氧酶HspB的结构研究

在蛋白晶体结构难以获得的情况下,通过设计突变体来获取6-羟基-3-琥珀酰吡啶单加氧酶Hsp B的结构信息。首先获取Hsp B蛋白的同源序列并进行比对,之后对Hsp B蛋白进行同源建模和从头建模,并与底物2,5-二羟基吡啶(HSP)进行对接模拟;通过分子模拟、序列比对和参考同源蛋白晶体三种方式,设计并构建Hsp B酶的25个突变体;通过突变体的表达纯化和酶动力学常数测定来研究Hsp B的结构性质。根据实验结果,推测FAD的正确结合在稳定Hsp B蛋白结构中具有重要的作用,同时推测底物HSP和辅酶NADH处于同一活性中心并与不同位点相互作用。吡啶衍生物是极具工业价值的化合物,生物催化法是合成吡啶衍生物的有效途径,而吡啶衍生物的生物催化研究较少,通过考察突变体的性质,推测了Hsp B的部分结构信息,为此类吡啶单加氧酶的工业改造和应用奠定了基础。     

Synthesis and NMR properties of novel 5,6-dihydroborauracil derivatives

Novel boron compounds - 5,6-saturated borauracil derivatives (4-bromo-5,6-dihydroborauracil, 4-hydroxy-5,6-dihydroborauracil and 4-methoxy-5,6-dihydroborauracil) are presented along with other boron compounds obtained from N-vinylurea: N-substituted β-boronic amino acid - 2-{[(dihydroxyborano-amino)(dihydroxyboranooxy)methyl]-amino}ethylboronic acid and substituted methoxy-borane O-[(1-amino-1-N-vinylamino)methyl]dihydroxyboronate.     

Ehretinine,a novel pyrrolizidine alkaloid from Ehretia aspera

The structure for ehretinine, 7-O-(p-methoxybenzoyl)-retronecanol, a new pyrrolizidine alkaloid isolated from leaves of Ehretia aspera has been established by a combination of spectroscopic and chemical methods. To our knowledge this constitutes the first report of the natural occurrence of a retronecanol ester.     

Buchananine,a novel pyridine alkaloid from Cryptolepis buchanani

A new alkaloid, buchananine, was isolated from the stems of Cryptolepis buchanani. Its structure was determined as 6-O-nicotinoyl-α-d-glucopyranose by chemical and spectroscopic investigations.     

Two 6-substituted 5,6-dihydro-alpha-pyrones from Ravensara anisata.

The leaves and bark dichloromethane extracts of Ravensara anisata showed antifungal activity against the yeast Candida albicans and the phytopathogenic fungus Cladosporium cucumerinum in bioautographic TLC assays. Activity-guided fractionation afforded two new alpha-pyrones: 6R*-(4R*-acetoxy-2S*-hydroxy- 8-phenyloctyl)-5,6-dihydro-2-H-pyran-2-one and 6R*-(2S*-acetoxy-4R*- hydroxy-8-phenyloctyl)-5,6-dihydro-2-H-pyran-2-one. Their structures have been established by NMR spectroscopy, chemical methods and X-ray crystallographic analysis. The antifungal activity against C. albicans and C. cucumerinum was determined for both compounds.     

A newly synthesized,potent tyrosinase inhibitor: 5-(6-Hydroxy-2-naphthyl)-1,2,3-benzenetriol

In searching for new agents with a depigmenting effect, we synthesized a derivative of resveratrol, 5-(6-hydroxy-2-naphthyl)-1,2,3-benzenetriol (5HNB) with a potent tyrosinase inhibitory activity. 5HNB inhibited mushroom tyrosinase with an IC₅₀ value of 2.95 μM, which is more potent than the well-known anti-tyrosinase activity of kojic acid (IC₅₀ = 38.24). The results of the enzymatic inhibition kinetics by Lineweaver–Burk analysis indicated 5HNB inhibits tyrosinase non-competitively when l-tyrosine was used as the substrate. Based on the strong inhibitory action of 5HNB, it is expected that 5HNB can suppress melanin production in which tyrosinase plays the essential role. Our expectation was confirmed by the experimentations with B16 melanoma cells in which 5HNB inhibited melanin production. We propose that 5HNB might have skin-whitening effects as well as therapeutic potential for treating skin pigmentation disorders.     

4-Hydroxy-3-methylbenzofuran-2-carbohydrazones as novel LSD1 inhibitors

Histone lysine specific demethylase 1 (LSD1 or KDM1A) is a potential therapeutic target in oncology due to its overexpression in various human tumors. We report herein a new class of benzofuran acylhydrazones as potent LSD1 inhibitors. Among the 31 compounds prepared, 14 compounds exhibited excellent LSD1 inhibitory activity with IC₅₀ values ranging from 7.2 to 68.8 nM. In cellular assays, several compounds inhibited the proliferations of various cancer cell lines, including PC-3, MCG-803, U87 MG, PANC-1, HT-29 and MCF-7. This opens up the opportunity for further optimization and investigation of this class compounds for potential cancer treatment.