Despite intense efforts to increase vaccine coverage, measles virus (MV) still causes significant morbidity and mortality in the world, sometimes as the result of severe, chronic, lethal disease. In an effort to develop therapies to supplement immunization strategies, a number of 5′-nor carbocyclic adenosine analogues were evaluated for anti-MV activity in CV-1 monkey kidney cells. Of those compounds tested, those either unsubstituted at C4 or possessing a hydroxyl, azido or amino substituent at that position were the most active, with particularly significant inhibition of MV, strain Chicago-1. The EC50 values against this strain ranged from <0.1 to 1 mg/ml, as determined by cytopathic effect reduction assay, and confirmed by neutral red uptake. By virus yield reduction assay (+)-(1 S,2S,3R,4S)-4-(6′-amino-9'H-purin-9′- yl)cyclopentane-1,2,3-triol (2) (-)-(1R,2S,3R)-1-(6′- amino-9'H-purin-9′-yl)-2,3-dihydoxycyclopent-4- ene (3) (-)-(1R,2S,3R)-1-(6-amino-9H-purin-9- yl)cyclopentane-2,3-dihydoxycyclopentane (5) and (-)-(1R,2R,3R,4S)-4-amino-1-(6-amino-9H-purin-9- yl)cyclopentane-2,3-diol (8) were the most potent compounds tested, all with EC90 values of <0.4 mg/ml. Compounds 3 and 5 were also tested against other MV strains, and similarly inhibited those strains except for four designated as Bil, Edmonston, SA and X-1108. Compound 8 did not potently inhibit these other MV strains. In addition, 3, 5 and 8 demonstrated synergistic (additive) inhibition of MV replication in combination with ribavirin at several concentrations. Compounds 3, 5 and 8 were also potent MV inhibitors even when added to infected cells 24 h after virus exposure. None of these three compounds was virucidal at concentrations that inhibited viral replication as determined by virus yield reduction assay. Most compounds tested were also not toxic at concentrations >100 mg/ml in actively growing and stationary-phase cells. Results suggest that these compounds may be clinically useful anti-MV virus agents.

Three flavonoid phospholipase A2 (PLA2) inhibitors were isolated from a MeOH extract of the bark of the Samoan medicinal plant Erythrina variegata. Two of these compounds, 4‘-hydroxy-3‘,5‘-diprenylisoflavonone (abyssinone V) (1) and 3,9-dihydroxy-2,10-diprenylpterocarp-6a-ene (erycrystagallin) (3), have been previously reported as antimicrobial agents from plants belonging to other Erythrina species. The isoflavonone 4‘-hydroxy-6,3‘,5‘-triprenylisoflavonone (2) is a new compound, and its structure was determined by spectroscopic techniques. The IC50 values for the PLA2 enzyme were 6, 10, and 3 μM for 1−3, respectively.

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A variety of olefins react with thiols in the presence of a catalytic amount of H-Rho-zeolite to afford the corresponding antiMarkovnikov addition products in good to excellent yields.The last few years have witnessed a considerable upsurge of interest in the area of zeolite induced organic transformations. 1 In a series of publications from our group, 2 we have exploited the catalytic potential of zeolites for various organic synthetic transformations, e.g. thioacetalization of carbonyl compounds, sulfoxidation of thioethers, deketalization, tetrahydropyranylation of alcohols, oxidative cleavage of tosylhydrazones, methoxymethylation of alcohols, chemo-and stereoselective epoxidation and acetylation of aldehydes etc. In continuation, we wish to report a mild, convenient and heterogeneous catalytic methodology for the synthesis of anti-Markovnikov addition products by the reaction of thiols and olefins using Rho-zeolite.In general, the protic acid 3 or Lewis acid 4 catalyzed addition of thiols across double bonds is known to give thioethers having structures which are in accordance with Markovnikov's rule. However, in the presence of freeradical initiator, thiols have been reported to add to double or triple bonds in anti-Markovnikov fashion by a freeradical mechanism. 5 A variety of hydroboration reagents developed for this reaction are also reported to give the anti-Markovnikov product. 6 However, the use of conventional protic or Lewis acid catalysts entails the problem of corrosivity, work-up and effluent pollution. Consequently, there is genuine need for an efficient and heterogeneous catalytic method for this reaction using inexpensive and nonpolluting reagents. Now we report that H-Rhozeolite serves as an efficient catalyst for the thiol addition to olefins (Scheme). SchemeThus, when the olefins were treated with thiols in the presence of catalytic amount of H-Rho-zeolite, the corresponding anti-Markovnikov products were obtained in good to excellent yields (Table). In a typical reaction procedure, to a stirred solution of olefin 1 (20 mmol) in nhexane (25 ml) were added H-Rho-zeolite (0.5 equivalent by wt. of olefin) and thiol 2 (25 mmol) and the mixture was refluxed with stirring for the indicated length of time (Table). The reaction was monitored by TLC and G. C. After the completion of reaction, zeolite was filtered off and washed with n-hexane; the filtrate was then washed with 10% aq. NaOH solution to remove excess thiol and then further washed with water, brine and dried over Na 2 SO 4 . Removal of solvent and subsequent silica gel column chromatography afforded the pure product 3 which was analyzed by 1 H NMR. Much to our surprise, an anti-Markovnikov addition product was obtained which otherwise formed in the presence of peroxide. Due to steric constraints on the diffusional path of the molecules imposed by the different structural feature of the zeolite, the more bulkier Markovnikov adduct could not be retained in the zeolite pore and presumably for this reason only the anti-Markovnikov product w...