George A. Kraus

A simple, effective, new, palladium-catalyzed conversion of enol silanes to enones and enals

Abstract Enol silanes derived from aldehydes and ketones are readily converted to the corresponding α,β-unsaturated carbonyl compounds by 10% Pd(OAc) 2 in the presence of one atmosphere of oxygen in DMSO as the solvent.

PHOTOSENSITIZATION IS REQUIRED FOR INACTIVATION OF EQUINE INFECTIOUS ANEMIA VIRUS BY HYPERICIN

Abstract— Hypericin, a photoreactive polycyclic quinone, was found to dramatically reduce infectivity of cell‐free stocks of equine infectious anemia virus. However, the antiviral activity of hypericin was completely dependent on the presence of light. Short periods of photosensitization resulted in a partial loss of reverse transcriptase activity and complete inhibition of viral infectivity. These results suggest that the photodynamic effect of hypericin interferes with more than one stage in the virus replication cycle.

Live-cell imaging of Pol II promoter activity to monitor gene expression with RNA IMAGEtag reporters

We describe a ribonucleic acid (RNA) reporter system for live-cell imaging of gene expression to detect changes in polymerase II activity on individual promoters in individual cells. The reporters use strings of RNA aptamers that constitute IMAGEtags (Intracellular MultiAptamer GEnetic tags) that can be expressed from a promoter of choice. For imaging, the cells are incubated with their ligands that are separately conjugated with one of the FRET pair, Cy3 and Cy5. The IMAGEtags were expressed in yeast from the GAL1, ADH1 or ACT1 promoters. Transcription from all three promoters was imaged in live cells and transcriptional increases from the GAL1 promoter were observed with time after adding galactose. Expression of the IMAGEtags did not affect cell proliferation or endogenous gene expression. Advantages of this method are that no foreign proteins are produced in the cells that could be toxic or otherwise influence the cellular response as they accumulate, the IMAGEtags are short lived and oxygen is not required to generate their signals. The IMAGEtag RNA reporter system provides a means of tracking changes in transcriptional activity in live cells and in real time.

Antiretroviral activity of synthetic hypericin and related analogs

Hypericin and pseudohypericin are naturally occurring polycyclic quinones which have recently been shown to inhibit the infectivity of several retroviruses, including human immunodeficiency virus. To better understand the antiviral mechanisms of these compounds, hypericin and a series of analogous quinones were synthesized and tested for anti-retroviral activity against equine infectious anemia virus (EIAV). Treatment of EIAV-infected cells with hypericin reduced the production of infectious virus by 99.99%. None of the analogs were found to inhibit virus replication. These results suggest that the complete ring structure of hypericin is required, but not sufficient, for antiviral activity.

An Improved Reductive Methylation Procedure for Quinones

Abstract The reductive methylation of quinones bearing electron donating groups such as hydroxyl or alkoxyl groups proceeds in good yields. The improved conditions greatly extend the scope of this useful reaction.

The synthesis of amino acids by 1,3-dipolar cycloadditions of azomethine ylides

Abstract Thiazolium ylides react with a variety of dipolarophiles to afford adducts. After filtration chromatography, a tricyclic adduct is obtained. The tricyclic adducts react with potassium t-butoxide/t-butanol to provide dihydropyrroles. The adducts also react with tributyltin hydride to form compounds in which the thiazolidine ring has been cleaved. These adducts can be hydrolyzed under acidic conditions to form pyrrolidines. The desulfurization procedure is significant in that none of the relative asymmetry derived from the dipolar cycloaddition is lost. The synthesis of α-allokainic acid has been achieved from adduct 16s .

Synthesis of the core bicyclic system of hyperforin and nemorosone

A direct synthesis of analogs of hyperforin and nemorosone containing the key bicyclic unit was accomplished from 2-carboxyethylcyclohexanone and benzoylcyclohexanone. Key steps included a manganic acetate-mediated cyclization and the formation of the beta-bromo enone.

Hypericum in infection: Identification of anti-viral and anti-inflammatory constituents.

The Iowa Center for Research on Botanical Dietary Supplements seeks to optimize Echinacea, Hypericum, and Prunella botanical supplements for human-health benefit, emphasizing anti-viral, anti-inflammatory, and anti-pain activities. This mini-review reports on ongoing studies on Hypericum. The Center uses the genetically diverse, well-documented Hypericum populations collected and maintained at the USDA-ARS North Central Regional Plant Introduction Station (NCRPIS), and the strength of research in synthetic chemistry at Iowa State University to tap natural diversity, to help discover key constituents and interactions among constituents that impact bioactivity and toxicity. The NCRPIS has acquired more than 180 distinct populations of Hypericum, with a focus on Hypericum perforatum L. (Hypericaceae), representing about 13% of currently recognized taxa. Center chemists have developed novel synthetic pathways for key flavones, acyl phloroglucinols, hyperolactones, and a tetralin that have been found in Hypericum, and these compounds are used as standards and for bioactivity studies. Both light-dependent and light-independent anti-viral activities have been identified by using bioactivity-guided fractionation of H. perforatum and a HIV-1 infection test system. Our Center has focused on light-independent activity, potentially due to novel chemicals, and polar fractions are undergoing further fractionation. Anti-inflammatory activity has been found to be light-independent, and fractionation of a flavonoid-rich extract revealed four compounds (amentoflavone, chlorogenic acid, pseudohypericin, and quercetin) that interacted in the light to inhibit lipopolysaccharide-induced prostaglandin E2 activity. The Center continues to explore novel populations of H. perforatum and related species to identify constituents and interactions of constituents that contribute to potential health benefits related to infection.

Bridgehead radicals in organic, chemistry. An efficient construction of the ABDE ring system of the lycoctonine alkaloids

Abstract The reaction of bridgehead radicals with allylic stannanes generates an intermediate for the synthesis of the ABDE ring of the lycoctonine alkaloids.

Quinone photochemistry. A general synthesis of acylhydroquinones

The synthesis of dihydroxy ketones such as 1 is usually accomplished by a sequence involving Friedel-Crafts acylation and hydrolysis.’ Disciplines Chemistry | Environmental Chemistry | Inorganic Chemistry | Organic Chemistry | Other Chemistry | Polymer Chemistry Comments Reprinted (adapted) with permission from The Journal of Organic Chemistry, 57(11); 3256-3257. Doi: 10.1021/jo00037a058. Copyright 1992 American Chemical Society. This article is available at Iowa State University Digital Repository: http://lib.dr.iastate.edu/chem_pubs/619 3256 J. Org. Chem. 1992,57,3256-3257 to give a continuous stream emanating from the condenser tip (for heat insulation the pressure-equalizing side arm of the addition funnel was wrapped with several layers of paper towel). The Teflon stopcock on the addition funnel was opened only slightly 80 as to minimize the entry of the hexane vapors from this inlet and yet fully drain all eluted solvent into the still-pot. Once started, the system was allowed to continue until all of the purple Cso had collected in the still-pot (20-30 h). The still-pot was then removed and the solvent evaporated6 to afford ca. 170 mg of pure (HPLC, W-vis) Cso which was separated from the boiling chips by dissolution in CS2 followed by suction filtration and precipitation from the filtrate with pentane. A new 2OOO-mL two-neck round-bottom flask containing 1.5 L of hexane was then installed and the above process repeated to elute pure C,o from the column (70 h). The solvent was evaporated, and 30 mg of pure (HPLC, UV-vis) CT0 was isolated. So far we have performed about 15 of these separations, all with high reproducibility. We believe the reason for the success of the separation lies not only in the use of lowest polarity solvents but also in the elevated temperaturelo due to the Soxhlet extraction process. It is possible that our results would not have been nearly as good had we tried the related apparatus of ref 6. Acknowledgment. We thank the National Science Foundation for support through Grants DMR-88-20933, DMR-91-11097, and CHE89-08323. We also thank Miklos Csuja for the glassware modifications. alumina, 1344-28-1. Registry NO. Cm, 9968596-8; C,or115383-22-7; C, 7440-44-0; (10) Pirkle and Welch (Pirkle, W. H.; Welch, C. J. J. Org. Chem. 1991, 56,6973) have found that better separations of CW/C,~ occur at higher temperature. Quinone Photochemistry. A General Synthesis of Acylhydroquinones George A. Kraus* and Masayuki Kirihara Department of Chemistry, Iowa State University, Ames, Iowa 50011 Received September 30, 1991 The synthesis of dihydroxy ketones such as 1 is usually accomplished by a sequence involving Friedel-Crafts acylation and hydrolysis.’ This sequence works well in