Jim-Min Fang

Structure and bioactivity of the polysaccharides in medicinal plant Dendrobium huoshanense.

Detailed structures of the active polysaccharides extracted from the leaf and stem cell walls and mucilage of Dendrobium huoshanense are determined by using various techniques, including chromatographic, spectroscopic, chemical, and enzymatic methods. The mucilage polysaccharide exhibits specific functions in activating murine splenocytes to produce several cytokines including IFN-gamma, IL-10, IL-6, and IL-1alpha, as well as hematopoietic growth factors GM-CSF and G-CSF. However, the deacetylated mucilage obtained from an alkaline treatment fails to induce cytokine production. The structure and bioactivity of mucilage components are validated by further fractionation. This is the first study that provides clear evidence for the structure and activity relationship of the polysaccharide in D. huoshanense.

A Concise and Flexible Synthesis of the Potent Anti-Influenza Agents Tamiflu and Tamiphosphor†

We report safer and more commercially viable synthetic methods for both antiinfluenza drugs Tamiflu and Tamiphosphor using bromobenzene as the starting material. This is an innovative procedure in which the bromine atom is converted to carboxyl or phosphonate groups at the later stage. All reactions are handled without using potentially hazardous intermediates or toxic reagents, and as most of the reactions occurred in a regioand stereoselective fashion to give crystalline products throughout the synthesis, the isolation procedures were relatively simple and cost effective.Like Tamiflu, Tamiphosphor can be taken orally, and functions as an inhibitor of the neuraminidase active site of the H5N1/ H1N1 viruses. However, Tamiphosphor proves to be more effective due to its higher enzyme inhibition. Survival rates and recovery rates of infected mice treated with Tamiphosphor both show better results.

SYNTHESIS OF XANTHENES, INDANES, AND TETRAHYDRONAPHTHALENES VIA INTRAMOLECULAR PHENYL–CARBONYL COUPLING REACTIONS

Benzaldehydes and acetophenones bearing tethered carbonyl chains underwent the intramolecular phenyl–carbonyl coupling reactions, by mediation of samarium diiodide and hexamethylphosphoramide, to afford the xanthenes and fused benzocarbocyclic compounds containing carbonyl and hydroxyl substituents.

Probing lectin and sperm with carbohydrate-modified quantum dots.

We report the encapsulation of quantum dots with biologically important β‐N‐acetylglucosamine (GlcNAc) in different ratios, together with studies of their specific/sensitive multivalent interactions with lectins and sperm by fluorimetry, transmission electron microscopy, dynamic light scattering microscopy, confocal imaging techniques, and flow cytometry. These GlcNAc‐encapsulated quantum dots (QDGLNs) specifically bind to wheat germ agglutinin, and cause fluorescence quenching and aggregation. Further studies of QDGLNs and the mannose‐encapsulated QDs (QDMANs) with sperm revealed site‐specific interactions, in which QDGLNs bind to the head of the sperm, while QDMANs spread over the whole sperm body.

Direct transformation of aldehydes to nitriles using iodine in ammonia water

Abstract Treatment of aromatic, heterocyclic, aliphatic, conjugated, and polyhydroxy aldehydes with iodine in ammonia water at room temperature for a short period gave the corresponding nitriles in high yields.

Uncommon diterpenes with the skeleton of six-five-six fused-rings from Taiwania cryptomerioides

Abstract Four diterpenoid aldehydes and one norditerpenoid ketone having the uncommon skeleton of six-five-six fused-rings were isolated from the leaves of Taiwania crytomerioides .

Stable Benzotriazole Esters as Mechanism-Based Inactivators of the Severe Acute Respiratory Syndrome 3CL Protease

Summary Severe acute respiratory syndrome (SARS) is caused by a newly emerged coronavirus that infected more than 8000 individuals and resulted in more than 800 fatalities in 2003. Currently, there is no effective treatment for this epidemic. SARS-3CLpro has been shown to be essential for replication and is thus a target for drug discovery. Here, a class of stable benzotriazole esters was reported as mechanism-based inactivators of 3CLpro, and the most potent inactivator exhibited a k inact of 0.0011 s−1 and a K i of 7.5 nM. Mechanistic investigation with kinetic and mass spectrometry analyses indicates that the active site Cys145 is acylated, and that no irreversible inactivation was observed with the use of the C145A mutant. In addition, a noncovalent, competitive inhibition became apparent by using benzotriazole ester surrogates in which the bridged ester-oxygen group is replaced with carbon.

Free radical type addition of toluenesulfonyl cyanide to unsaturated hydrocarbons

Abstract By catalysis of AIBN, tosyl cyanide adds in a regio- and stereoselective manner to unsaturated hydrocarbons, including alkenes, dienes and 1-hexyne. Accompanied intramolecular cyclization and ring cleavage were effected in reactions with norbornadiene, 1,5-cyclooctadiene and pinenes.

Diterpenes and related cycloadducts from Taiwania cryptomerioides

Seven new compounds were isolated from the leaves of Taiwania crypomerioides. Taiwaniaquinone D and taiwaniaquinone E are diterpenes having a six-five-six fused ring skeleton. Taiwaniadduct A is a [4 + 2] cycloaddition product of β-myrcene and taiwaniaquinone A. Taiwaniadduct B and taiwaniadduct C are isomers derived from [4 + 2] cycloadditions of trans-ozic acid and taiwaniaquinone A. Taiwaniadduct D is formally an ene reaction product of taiwaniadduct B. Taiwaniadduct E is a [5 + 2] cycloaddition product of taiwaniaquinone A and trans-ozic acid. The structure determination of these new compounds was based on spectral analyses and chemical transformation. A crystalline compound, prepared by bismethylation of taiwaniadduct D, was analysed by X-ray diffraction to establish the stereochemistry.

Design, synthesis, and evaluation of 3C protease inhibitors as anti-enterovirus 71 agents

Abstract Human enterovirus (EV) belongs to the picornavirus family, which consists of over 200 medically relevant viruses. A peptidomimetic inhibitor AG7088 was developed to inhibit the 3C protease of rhinovirus (a member of the family), a chymotrypsin-like protease required for viral replication, by forming a covalent bond with the active site Cys residue. In this study, we have prepared the recombinant 3C protease from EV71 (TW/2231/98), a particular strain which causes severe outbreaks in Asia, and developed inhibitors against the protease and the viral replication. For inhibitor design, the P3 group of AG7088, which is not interacting with the rhinovirus protease, was replaced with a series of cinnamoyl derivatives directly linked to P2 group through an amide bond to simplify the synthesis. While the replacement caused decreased potency, the activity can be largely improved by substituting the α,β-unsaturated ester with an aldehyde at the P1′ position. The best inhibitor 10b showed EC50 of 18nM without apparent toxicity (CC50 >25μM). Our study provides potent inhibitors of the EV71 3C protease as anti-EV71 agents and facilitates the combinatorial synthesis of derivatives for further improving the inhibitory activity.