Synthesis of novel benzoxaborole-containing phenylalanine analogues

The synthesis of novel benzoxaborole-containing phenylalanine analogues 2 and 3 has been developed. The key steps involve the preparation of appropriate precursors from the readily available amino acids and the formation of benzoxaborole ring directly in the corresponding amino acid fragment. The resulting compounds 2-3 show improved water solubility at physiological pH, suggesting their potential use as boron delivery agents for boron neutron capture therapy.     

Synthesis of novel pyrimidine nucleoside analogues

Two new tetrazolopyrimidinedeoxynucleosides were synthesized and their physico-chemical data are described. Results of preliminary analyses of their biological properties are also reported.     

Synthesis of novel halogenated cryptolepine analogues

Cryptolepine (5‐N‐methyl‐10‐H‐indolo[3,2‐b]quinoline) is an indoloquinoline alkaloid present in the roots of Cryptolepis Sanguinolenta. In its hydrochloride form the alkaloid presents a number of bioactivities. The alkaloid also has cytotoxic properties that are likely to be due to its abilities to intercalate into DNA and inhibit the enzyme topoisomerase II, as well as the synthesis of DNA. In this research project five novel analogues of cryptolepine were chosen for synthesis.     

Synthesis and NMR characterization of a novel crown-ether ring-fused uridine analogue

The chemical synthesis and ¹H NMR analysis of a novel bicyclic uridine derivative, with a 18-crown-6 ether moiety fused at the ribose 2- and 3-positions, as first example of a hitherto unknown class of ribose-modified nucleosides, are here described. NMR-based conformational analysis studies showed for the modified nucleoside a marked preference for an N-type sugar puckering and the nucleobase in the anti conformation, with the uracil favouring the coordination of a sodium ion hosted in the crown ether.     

Synthesis and antitumor activity of novel salvicine analogues

Systematic structure modification of the side train of the lead compound saprothoquinone provides a series of salvicine analogues,fifteen of them were first reported.Some compounds were demonstrated potent cytotoxicity against tumor cells with the 50%inhibition concentration in the micromolar range.Furthermore some compounds showed potent topoisomeraseⅡinhibitory effects.The preliminary structure-activity relationship of saprorthoquinone analogues was discussed according to their cytotoxicity against thr...     

Synthesis and cytotoxic activity of novel curcumin analogues

Five novel curcumin analogues bearing different substituents at 4-position of phenyl group were synthesized. Their structures were confirmed by NMR and HRMS spectrum. Their cytotoxic activities against six tumor cell lines were tested by the standard MTT assay in vitro. The results indicated that four analogues （1A-1C, 1E） with solubilizing moieties showed selective potent cytotoxicity against HepG2, HeLa and CT26 cell lines, and analogue 1A and 1C exhibited more potent cytotoxicity than curcumin against CT26 cell line. It was suggested that introduction of appropriate substituents to 4-position of phenyl group might be a potential option for structural modification of curcumin.     

Synthesis of novel isoxazolidine analogues of homonucleosides

A general method for the synthesis of nucleobase-derived nitrones 4a–e by treatment of N-(2-oxoethyl)nucleobases with N-methylhydroxylamine is reported. The nitrones 4a–e were applied in the synthesis of isoxazolidine homonucleosides. Moderate diastereoselectivities (de 28–82%) were observed for cycloadditions between nitrones 4a–e and allyl alcohol with cis-isoxazolidines predominating. The stereochemistry of the substituted isoxazolidines was established based on an analysis of 2D NOE experiments for uracil-containing cycloadducts 6a and 7a. Cycloadditions of uracil-based nitrone 4a with vinyl-, allyl-, vinyloxymethyl- and allyloxymethylphosphonates gave the respective phosphonylated cis-isoxazolidines as the major adducts.     

Synthesis of novel structurally simplified estrogen analogues

A library of 17 novel estrogen analogues 3 and 4 containing different substituents at rings A and D (steroid nomenclature) was prepared in a five- to seven-step synthesis. The key transformation is a Sonogashira-coupling of cyclic vinyl iodides of type 7 or 8 with phenylacetylenes of type 9. Reduction of the keto function in 3 led to the estradiol analogue 5.     

Synthesis of novel nithiazine analogues containing the 1,4-dihydropyridine structure,and their bioactivity as insecticides

A series of novel nithiazine analogues bearing the 1,4-dihydropyridine structure have been designed and synthesized by reaction of nithiazine, malononitrile or ethyl cyanoacetate, and benzaldehyde. The synthesized compounds were identified by ¹H NMR and IR spectroscopy, and elemental analysis. Preliminary bioassays indicated that most of the compounds had moderate insecticidal activity against Aphis craccivora. The relationship between molecular structure and biological activity is discussed.     

Synthesis and biological evaluation of novel macrocyclic paclitaxel analogues

[reaction: see text] This work describes the synthesis of two novel macrocyclic taxoid constructs by ring-closing olefin metathesis (RCM) and their biological evaluation. Computational studies examine conformational profiles of 1 and 2 for their fit to the beta-tubulin binding site determined by electron crystallography. The results support the hypothesis that paclitaxel binds to microtubules in a "T" conformation.     

新型类嘌呤脱氧核糖核苷类化合物的合成

以1,3,5-三-O-苯甲酰基-2-脱氧-2-β-氟-α-D-核糖为原料,通过溴代、与4-氯吡咯[2,3-d]嘧啶的钠盐偶合、4-氯的氨基化等反应,设计合成了一系列具有新型结构的4-取代-9-(2′-脱氧-2′-β-氟-β-D-呋喃糖基)吡咯[2,3-d]嘧啶类化合物,其化学结构经核磁共振、高分辨率质谱分析确证;并且初步探讨了反应条件和反应机理.结果表明,以无水四氢呋喃为溶剂,密闭高压回流反应,反应产率较高.     

Synthesis and biological evaluation of novel fumagillin and ovalicin analogues

A promising approach among the numerous efforts to cure cancer is the interruption of the tumour-induced formation of new blood vessels (angiogenesis). By suppressing angiogenesis with drugs, the tumour can neither grow to a life threatening size, nor metastasize. The natural product fumagillin 1 and the structurally related ovalicin 2 are two of the most potent anti-angiogenic compounds. Here, we report the design and synthesis of novel fumagillin and ovalicin analogues lacking reactive epoxy functionalities, which were thought to be responsible for the severe toxic side-effects observed. We also report a new synthetic approach and the determination of the anti-angiogenic properties of these compounds in endothelial cells.     

Synthesis and biological evaluation of novel benzoxazinic analogues of ellipticine

Original 1,4-benzoxazine analogues of ellipticine were prepared using a general synthetic route that relied on an anionic ring annulation as the key transformation. The interest of this approach lies on the possibility of an easy entrance to a wide range of derivatives from the phenol intermediate. In addition, this synthetic strategy offers a smart access to diverse structurally related heteroaryl annulated carbazole analogues of ellipticine just by replacing the starting heterocyclic core. Antiproliferative activities of newly synthesized derivatives were evaluated toward tumor cell lines.     

Synthesis and structure of novel organocycloborates

A series of alpha,omega-boryl(bromo)alkanes of the general formula R2B-(CH2)n-Br (n = 3, 4, 5, 6) was obtained in high yield following a standard hydroboration protocol. Upon treatment with Mg turnings and formation of the respective Grignard species, all alkanes with n = 4 to 6 underwent an unprecedented boron-centered cyclisation reaction with formation of boratacyclopentanes, -hexanes, and -heptanes, respectively. All new compounds were isolated in high yields as colourless, crystalline materials and characterised in solution by multinuclear NMR spectroscopy. Four representative examples were chosen for X-ray diffraction studies, thus providing the first structurally characterised ring systems of that size at a tetraalkyl borate centre.     

Synthesis of novel migrastatin and dorrigocin A analogues from D-glucal

The synthesis of a range of analogues of the migrastatin macrolide core has been achieved from tri-O-acetyl-D-glucal in order to facilitate structure-activity studies. Efficient macrolactone formation was achieved in the presence of a reactive olefin, by increasing steric hindrance in the olefin environment. Acyclic analogues of migrastatin, structurally related to dorrigocin A, have also been prepared from D-glucal. The dorrigocin A analogues were prepared using the combination of the cross metathesis of ethyl 6-heptenoate with a glycal derivative and a subsequent allylic rearrangement-alkene isomerisation reaction (Perlin reaction). A synthetic route is thus provided that will enable dorrigocin A analogues to be prepared in parallel to migrastatin analogues in the search for novel anti-cancer and anti-arthritic therapeutics. Biological evaluation of one migrastatin and one dorrigocin A sugar derived analogue show that they inhibit proliferation and serum-induced migration of tumour and synovial cells at higher concentrations than evodiamine. Dorrigocin A analogues displayed similar potency to analogues of the migrastatin core.     

Synthesis of novel anthracene derivatives of isoxazolino-carbocyclic nucleoside analogues

The synthesis of isoxazolino-carbocyclic nor-nucleosides incorporating an anthracene moiety was properly tuned through nitrosocarbonyl intermediates chemistry, and a variety of analogues were attained starting from stereodefined heterocyclic aminols through the linear construction of purine heterocyclic rings. The synthesis hinges on the exo selective 1,3-dipolar cycloaddition of the stable anthracenenitrile oxide to the N-benzoyl-2,3-oxazanorborn-5-ene and simple elaborations of the cycloadducts. A selection of nucleoside derivatives were initially tested for their inhibitory activity against a variety of viruses, including Hepatitis B and C, Human Papilloma virus as well as Influenza viruses of type A and B. Modest anti-viral activities were observed in Hepatitis assays while the activities in the cases of Influenza viruses were almost negligible. Good anti-viral activity was found for compound 11bC with no cellular toxicity at the dose tested in the case of Human Papilloma virus.     

Synthesis of novel analogues of zanamivir as neuraminidase inhibitors

<正>A versatile synthesis of novel zanamivir analogues modified at C-4 and C-8 positions was described.The formation of amides from the acid with corresponding amines,followed by click chemistry generated the triazole substituted compounds as novel analogues of neuraminidase inhibitors in good yields.