Research Interest:

Antitumor and Antiviral Agents

At present we are engaged in the total synthesis of a large number of active antitumor 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. We are also investigating new methods for the preparation of l-carbohydrates and their corresponding modified nucleosides, e.g., l-5-F ddC, which have shown strong antiviral activity. As possible reagents for antisense oligonucleotide therapy, we are preparing both l-DNA and l-RNA. Finally we are preparing several isonucleosides and 4'-substituted 2'-deoxynucleosides as potential antiviral agents.

Other Biologically Active Compounds

The synthesis of several biologically active alkaloids is currently under investigation. Included among our 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. We are also pursuing total syntheses of some antiulcer compounds (the plaunol class of clerodane diterpenes), antiinflammatory agents (pseudopterosin A), and the unusual ketosterols xestobergsterol and contignasterol, which are inhibitors of histamine release. We are developing new processes for the efficient synthesis of various cardioactive agents, e.g., ouabain and several naturally occurring natriuretic agents. We have several collaborative programs, e.g., 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 finally to determine the structures and mechanism of action of several naturally occurring natriuretic agents.

New Synthetic Methods and Physical Organic Chemistry

We are studying several epoxide rearrangements, e.g., the preparation of asymmetric quaternary aldehydes from tertiary vinyl oxiranes. By this method, we have also determined that a benzylic cation is more stable than an allylic one, e.g., the ethenyl phenyl oxirane gave the single optically active product shown below. We 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. We are now extending this reaction to the synthesis of polypropionates by an iterative process so that compounds such as erythromycin and rifamycin could be prepared.
We are also studying the use of radical cyclization-fragmentation processes for the synthesis of several natural products of biological interest. Finally, we 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 one to carry out a wide variety of cyclizations, including cyclizations to produce 4- and 8-membered rings. We are also studying the possibility of asymmetric induction in these processes.

Detailed Biography:

Mike Jung received his Bachelor of Arts in 1969 from Rice University, doing research with Richard Turner, and then his PhD in 1973 from Columbia, where he worked with Gilbert Stork. After a one-year NATO postdoctoral fellowship with Albert Eschenmoser at the ETH in Zurich, he joined the faculty at UCLA in 1974. He has risen through the ranks at UCLA and is now a Distinguished Professor of Chemistry. He has served as a reviewer of proposals for various organizations, e.g., NSF, PRF, NIH Medicinal Chemistry Study Section, Research Corporation and others. He is on the Scientific Advisory Boards of several pharmaceutical firms and consults currently for more than 20 industrial laboratories in both the biotech and big pharma settings. Professor Jung is an authority on synthetic organic and medicinal chemistry and has more than 25 patents arising from both his consulting activities and his own research. His current interests include the easy preparation of hindered systems via both Diels-Alder reactions using a new mixed Lewis acid catalyst and via an unusual formal [3,3]-sigmatropic rearrangement. He has also pioneered the use of epoxide rearrangements in synthesis (e.g., the non-aldol aldol) and has investigated new types of gem-disubstituent effects in synthesis. He has published more than 250 articles in refereed journals and has given over 470 lectures on his research, including lectures in German and French. Finally one of his recent compounds is in Phase 1/2a clinical trials for the treatment of hormone refractory prostate cancer.