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Dissertation Information for Shuli Mao

NAME:
- Shuli Mao

DEGREE:
- Ph.D.

DISCIPLINE:
- Chemistry

SCHOOL:
- Emory University (USA) (2006)

ADVISORS:
- Dennis C. Liotta

COMMITTEE MEMBERS:
- Albert Padwa
- Lanny S. Liebeskind

MPACT Status: Fully Complete

Title: Part I: Synthesis and anti-HIV activity of novel cyclobutyl nucleoside and nucleotide analogs. Part II: Synthesis of enantiomerically pure D-FDOC ((+)-2\',3\'-dideoxy-5-fluoro-oxacytidine)

Abstract: Part I of this dissertation describes the synthesis and anti-HIV activity of several novel cyclobutyl nucleoside analogs as anti-HIV agents. The synthesis of these analogs features a [2+2] ketene cycloaddition to construct the carbocyclic four-membered ring and an efficient S N 2 strategy to couple the four-membered ring with a variety of nucleoside bases, including pyrimidine and purine bases. The EC 50 values in human PBM cell lines ranged from 27.7 to 100 ìM with no toxicity in PBM, CEM and Vero cells up to 100 ìM. Interestingly, all the cyclobutyl pyrimidine (uracil and cytosine) nucleoside analogs did not show any anti-HIV activity, however, some of the cyclobutyl purine (adenine and guanine) nucleoside analogs did show some mild anti-HIV activity. The fluorine substitution on the four-membered ring did not change the anti-HIV activity significantly compared with that without fluorine substitution. In addition, insertion of an extra CH 2 group either on the nucleoside base portion or the 3\'-hydroxymethyl portion resulted in the loss of anti-HIV activity for the adenine analogs. Part II of this dissertation discusses the improvement on the enantiomeric purity of D-FDOC, a very potent anti-HIV candidate, by using a tandem kinetic resolution/crystallization technique. In addition, the unwanted enantiomer was racemized to give an equal amount of the D- and L-enantiomer by subjecting the starting material to a similar coupling reaction conditions.

MPACT Scores for Shuli Mao

A = 0
C = 0
A+C = 0
T = 0
G = 0
W = 0
TD = 0
TA = 0
calculated 2008-03-16 15:59:10

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