At present, Dr. Michael Jung's lab is engaged in the total synthesis of a large number of active anti-tumor and antiviral agents.
The current cytotoxic targets include dichlorolissoclimide, tedanolide and 13-deoxytedanolide, aplysiapyranoids A-D, discodermide, dysidiolide, sclerophytin A, cylindramide A and halomon and its alkene derivatives. The antiviral compounds are oxetanocin A and its analogues, both the carbocyclic ones, e.g., cyclobut-A and G, and the C-oxetanocins (related to oxetanocin H), methylene-expanded oxetanocins, several modified N-nucleosides (2', 3'-dideoxycytidine and analogues, AZT, d4T and their analogues, l-3-TC), carbovir and the cyclophellitols. Jung and his colleagues are also investigating new methods for the preparation of l-carbohydrates and their corresponding modified nucleosides (e.g., l-5-F dd), which have shown strong antiviral activity. The researchers are preparing both l-DNA and l-RNA as possible reagents for antisense oligonucleotide therapy. Finally, the researchers are preparing several isonucleosides and 4'-substituted 2'-deoxynucleosides as potential antiviral agents.
Jung is currently investigating the synthesis of several biologically active alkaloids. Included among his synthetic goals are the following the novel dimeric bis-amino acid isodityrosine, the antitumor agents bouvardin and deoxybouvardin, the ACE inhibitor K-13, the platelet aggregation inhibitor herquline and the antifungal agent piperazinomycin. He and his colleagues are also pursuing total syntheses of some antiulcer compounds (the plaunol class of clerodane diterpenes), anti-inflammatory agents (pseudopterosin A) and the unusual ketosterols xestobergsterol and contignasterol, which are inhibitors of histamine release. The researchers are developing new processes for the efficient synthesis of various cardioactive agents (e.g., ouabain) and several naturally occurring natriuretic agents. Jung and his associates have several collaborative programs to prepare modified peptides as potential inhibitors of carboxy methyl transferases, to develop a new method of delivering antibacterial agents to resistant bacterial strains and to determine the structures and mechanism of action of several naturally occurring natriuretic agents.
Jung's laboratory is studying several epoxide rearrangements - the preparation of asymmetric quaternary aldehydes from tertiary vinyl oxiranes, for example. By this method, the researchers have also determined that a benzylic cation is more stable than an allylic one. The researchers have also developed a new method for the preparation of aldols by a non-aldol process. Thus, conversion of an aldehyde to the epoxy alcohol via Wittig reaction and reduction followed by Sharpless epoxidation generates the substrate for the rearrangement which is effected by treatment with trialkylsilyl triflates and base to give the protected aldol products in high yield. Jung's lab is now extending this reaction to the synthesis of polypropionates by an iterative process so that compounds such as erythromycin and rifamycin could be prepared.
Jung and his colleagues also are studying the use of radical cyclization-fragmentation processes for the synthesis of several natural products of biological interest. The researchers are investigating the synthetic potential of substituent effects (gem-dialkyl, -dialkoxy, -dithioalkoxy, -dicarboalkoxy, bis (dialkylamino), etc.) and polar solvent effects on cyclizations, including the novel acceleration of the intramolecular Diels-Alder reactions of furfuryl methyl fumarates by the use of polar solvents. Dialkoxy substitution, both gem and vic, allows researchers to carry out a wide variety of cyclizations, including cyclizations to produce 4- and 8-membered rings. Jung's lab is also studying the possibility of asymmetric induction in these processes.
Selected Cancer-Related Publications:
Jung ME, Murakami M. Total synthesis of (+/-)-hedychilactone B: stepwise allenoate diene cycloaddition to prepare trimethyldecalin systems. Org Lett. 2007 Feb 1;9(3):461-3.
Jung ME, Murphy JM. Functional Group Selectivity in Reactions of Epoxides with Tungsten Hexachloride Tetrahedron Lett. 2007;48: 8388-8391.
Jung ME, Yoo D. Synthesis of the C1-C12 fragment of the tedanolides. Aldol-non-aldol aldol approach. Org Lett. 2007 Aug 30;9(18):3543-6. Epub 2007 Aug 3.
Tsay JM, Trzoss M, Shi L, Kong X, Selke M, Jung ME, Weiss S. Singlet oxygen production by Peptide-coated quantum dot-photosensitizer conjugates. J Am Chem Soc. 2007 May 30;129(21):6865-71. Epub 2007 May 4.
Jung ME, Murakami M. Total synthesis of (+/-)-hedychenone: trimethyldecalin terpene systems via stepwise allenoate diene cycloaddition. Org Lett. 2006 Dec 7;8(25):5857-9.