Research Summary
Qian Zhang
My research focuses on the development of molecules with biological activities in various areas.
During the course of my research, I also develop new methodologies to facilitate the synthesis of
complex bioactive molecules.
Project 1: Synthesis of biological active 1,4-naphthoquinone derivatives
Based on a [2+3] cycloaddition reaction, several
new synthetic methodology was developed
(Figure 1). One of the method enables the
synthesis of bioactive 1-alkyl-1H-naphtho[2,3d][1,2,3]triazole-4,9-diones
and
N-aryl-2aminomethylene-1,3-indanediones using water as
the solvent with good yields and minimum
requirement of purification. For the other method,
by employing Lewis acid, synthesis of N-alkyl 2aminomethylene-1,3-indanediones
and
2alkylamino-1,4-naphthoquinones is achieved in
one-pot fashion. The new methodologies are
feasible for scale-up synthesis of compounds
with biological interests. These work has been
published in two Tetrahedron Letters papers.
Project 2: Synthesis of biological active carbohydrates based antimicrobial agents
Bacterial resistance has become a more and more
serious problem. It has been found that chemical
modification, such as adding a linear carbon
chain, can generate so called “amphiphilic
carbohydrates” which could possibly show
enhanced antibacterial properties or even show
antifungal activity. I plan to use green and
completely renewable unprotected natural sugars,
along with acyl chloride differing at chain length,
through a one-step reaction, to build a library of
carbohydrate esters. This library of compounds
will be tested for antimicrobial effect (Scheme 1,
Step 2). I have already identified one lead
compound which is both antibacterial and
antifungal. The future work will be focused on
developing a green synthesis for this lead
compound.
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Project 3: Synthesis of amphiphilic kanamycin derivatives as antifungal agents
A concise and novel method for site-selective alkylation of tetraazidokanamycin has been
developed that leads to the divergent synthesis of three classes of amphiphilic kanamycin
derivatives (Scheme 2). These new amphiphilic kanamycin derivatives bearing different alkyl
chains length has been synthesized and tested as antibiotics. Surprisingly, the antibacterial effect
of the synthesized kanamycin derivatives decline or disappear compared with the original
kanamycin A, but some of the compounds show very strong activity as antifungal agents. This
part of work is in manuscript preparation stage.
Project 4: Using fluorogenic probes for the investigation of selective biomass degradation
by fungi
A
library
of
fifteen
commercially purchased and
synthetic fluorogenic probes
was employed for the
investigation of biomass
degradation using extracts of
white-rot fungi (Figure 2).
These probes were selected or
designed to mimic the
dominant linkages in celluloses, hemicelluloses, and lignin, the three most abundant
polymers found in biomass. The results show that white-rot fungi display a high preference
for cleaving mannose- and glucose-based probes, which mimic hemicelluloses. Low
degrees of cleavages were noted for xylose- and cellobiose-based probes. No cleavages
were observed for probes that mimic the linkages in lignin. The observed rate of
degradation is the following: hemicellulose-based probes ≫ cellulose-based probes >
lignin-based probes. This finding suggests that by controlling the time of incubating the
fungal enzymes and biomass, it is possible to selectively release and separate
hemicelluloses while keeping cellulose and lignin intact. In summary, this study supports
the use of fungal enzymes as a tool for developing an effective and green process for
isolating and utilizing hemicelluloses from biomass.
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