|
|
Type of Document Dissertation Author LI, Fangzheng Author's Email Address fli1@nd.edu URN etd-12072006-195133 Title New Synthetic Applications of Nitroso Diels-Alder Reactions Degree Doctor of Philosophy Department Chemistry and Biochemistry Advisory Committee
Advisor Name Title Richard E. Taylor Committee Chair Marvin J. Miller (Advisor) Committee Co-Chair Olaf Wiest Committee Member Xavier Creary Committee Member Keywords
- Nitroso Diels-Alder reaction
- Carbocyclic uracil polyoxin C
- (+)-Streptazolin
- Bioactive natural product derivatization
- Nitroso pyridines
- Total synthesis
Date of Defense 2006-10-26 Availability restricted Abstract NEW SYNTHETIC APPLICATIONS OF NITROSO DIELS-ALDER REACTIONSAbstract
by
Fangzheng Li
The focus of this dissertation is to develop new synthetic applications of nitroso Diels-Alder reactions, which have been powerful synthetic tools for the formation of 1,4-C-O and C-N bonds in a single step. Four projects have been evolved from this main research theme.
In Chapter two, efficient and practical chemoenzymatic syntheses of both enantiomerically pure 4-Boc-aminocyclopent-2-ene-1-ols are presented based on an acylnitroso Diels Alder reaction approach. Starting from one enantiomer, total syntheses of (+)-carbocyclic uracil polyoxin C and its α-epimer were accomplished in eight steps. The synthesis incorporates a Pd(0)-catalyzed allylic alkylation, a mild reduction of an α-nitro ester and a modification of Shaw and Warrener�s procedure for uracil formation.
Starting from the other enantiomer, the stereoselective total synthesis of a lipophilic antibiotic, (+)-streptazolin is described in Chapter 3. The synthetic sequence highlights an intramolecular aldol condensation strategy to construct the piperidine core and a silicon-tethered ring closing metathesis strategy to install the Z exocyclic ethylidene side chain of streptazolin. The overall yield was 4.8% for a total of 16 steps. Meanwhile, a highly efficient and selective pyridine nitroso DA reaction was used to synthesize novel streptazolin derivatives.
In the next Chapter, the stabilized iminonitroso Diels-Alder reaction, particularly the pyridine NDA (nitroso Diels-Alder) reaction, is demonstrated to be a remarkably efficient method for derivatization of complex diene-containing natural products. Natural products, turimycin H3, ergosterol, reductiomycin, colchicine and thebaine were found to react with nitrosopyridines in a highly efficient and completely regio- and stereo-selective fashion. In most cases, NDA cycloadducts were obtained in more than 90% purity without any work-up or purification. Meanwhile, pyridine NDA reactions of piperine, oligomycin A, rifampicin quinone and flavofungin were also investigated. Interestingly, apoptolidin was found to undergo ene reaction instead of DA reaction again in a highly efficient and stereroselctive fashion. Preliminary bioactivity evaluations of cycloadducts are also presented.
Finally, efforts toward developing a catalytic enantioselective acylnitroso Diels-Alder reaction by using three approaches are discussed in Chapter 5. Those approaches include a Cu Lewis acid based dual function catalyst system, a gem-C-acetoxynitroso DA reaction as an acyl nitroso DA reaction equivalent and a use of organocatalysts to incorporate chiral elements into the diene part of the acylnitroso DA reaction.
Files
Filename Size Approximate Download Time (Hours:Minutes:Seconds)
28.8 Modem 56K Modem ISDN (64 Kb) ISDN (128 Kb) Higher-speed Access LiFZ122006.pdf 2.07 Mb 00:09:35 00:04:56 00:04:19 00:02:09 00:00:11 indicates that a file or directory is accessible from the campus network only.