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Dissertation Information for Hongjun Zhang

NAME:
- Hongjun Zhang

DEGREE:
- Ph.D.

DISCIPLINE:
- Chemistry

SCHOOL:
- Emory University (USA) (2006)

ADVISORS:
- Albert Padwa

COMMITTEE MEMBERS:
- Dennis C. Liotta
- Simon B. Blakey

MPACT Status: Fully Complete

Title: Application of the Intramolecular Diels-Aider Reaction (IMDAF) of 2-Amidofurans toward Alkaloid Synthesis

Abstract: The synthetic value of employing the intramolecular Diels-Alder reaction (IMDAF) of 2-substituted amdiofurans as a critical synthetic step for alkaloid synthesis has been investigated. Using this protocol, the successful synthesis of four biologically important alkaloids lycoricidine, 7-deoxypancratistatin, strychnopivotine, and strychnine was accomplished. This method was also used as an approach toward the construction of the Ergoline skeleton. The total synthesis of lycoricidine and 7-deoxypancratistatin, two congeners of the Amaryllidaceae family, featured a highly efficient one-pot Stille coupling/IMDAF cascade to assemble the core skeleton. The correct relative stereochemistry at the C 3 , C 4 , and C 4a positions was set via a stereocontrolled dihydroxylation reaction followed by an N -acyliminium ion reduction. Utilization of the carbomethoxy group allowed the key IMDAF reaction to occur under mild conditions, thereby allowing the successful isolation of the cycloadduct. The presence of the carbomethoxy group also directed the stereoselective reduction of the N-acyliminium ion obtained by the ring opening reaction. A tandem hydrolysis/ decarbonylation/ elimination sequence was developed so as to install the requisite C 1 -C 10b double bond of lycoricidine. The synthesis of lycoricidine was achieved in 14 steps with an overall 12.6% yield. In the synthesis of 7-deoxypancratistatin, a stereospecific decarbonylation was carried out using Rh(PPh 3 ) 3 Cl to set the crucial trans -fused B,C ring junction present in the target molecule. The total synthesis of strychnopivotine and strychnine featured the rapid construction of the ABCE tetercyclic skeleton by an IMDAF reaction of a 2-substituted amidofuran containing a tethered indole as the dienophile. The C 16 carbonyl group derived from the amidofuran was utilized to facilitate E-ring closure by a Pd-catalyzed enolate coupling. Incorporation of the crucial C 17 aldehyde group present in strychnine could be accomplished by a Wittig olefination of the keto group. Both syntheses were completed in a highly concise fashion. Thus, the synthesis of strychnine was carried out in 14 steps while 13 steps was necessary for the first total synthesis of strychnopivotine. The routes developed in this Ph D thesis will allow for the future syntheses of many other Strychnos alkaloids. Finally, an efficient approach toward the formation of the tricyclic core of the Ergot alkaloids was developed by employing a sequential aminodiene Diels-Alder cycloaddition reaction. Substitution on the aryl A ring of the Ergot alkaloids occurred by employing various substituted 2-amidofurans as the starting material. Unfortunately, total synthesis of lysergic acid was ultimately thwarted by an uncooperative Heck reaction.

MPACT Scores for Hongjun Zhang

A = 0
C = 0
A+C = 0
T = 0
G = 0
W = 0
TD = 0
TA = 0
calculated 2008-02-03 19:37:09

Advisors and Advisees Graph