Pactamycin, first reported in 1962, is a potent antitumor antibiotic produced by the soil bacterium Streptomyces pactum. Structurally, it contains a cyclopentitol core unit, a 3-aminoacetophenone (3AAP), a 6-methylsalicylic acid (6-MSA), and a N,N-dimethyl urea. The aminocyclopentitol ring is derived from glucose, possibly via N-acetyl glucosamine (GlcNAc), the 3-aminoacetophenone (3AAP)...
In this report, three studies are presented that aid in the development of drug discovery and their synthesis. In each, the importance of the marriage between computations and experiments is highlighted. Continued efforts in this vein are essential for future efforts towards improving human health.
The first case study investigated...
Studies toward synthesis of subunits of sanglifehrin A, an immunosuppressant featuring a highly substituted [5,5]-spirolactam moiety as well as a 22-membered macrocycle are described. The macrolactone contains a peptidic backbone characterized by an unusual [beta]-substituted (S)-piperazic acid and (S)-m-hydroxyphenylalanine units. These studies resulted in the synthesis of advanced intermediate 358...
My work on computing complex catalyzed organic transformations reveals that only a few subtle chemical factors, e.g. non-classical hydrogen bonding, (hyper)conjugation and steric effects, common across different catalyst manifolds are critical for catalysis and selectivity. Rational manipulation and exploitation of these factors has led to improved catalyst designs, which has...
Part I: Racemic and asymmetric syntheses of a new substance with prospective antidepressant properties were achieved. In vitro assays with synthetic racemates (±)-25 and (±)-26 suggested that the former is a relatively selective inhibitor of serotonin transporter whereas the latter is a more balanced inhibitor of both serotonin and norepinephrine...
Studies toward the total syntheses of highly potent cytotoxic alkaloids
including the bromopyrrole alkaloids and indole alkaloids were conducted and are
described. Studies carried out in the course of this dissertation consist of five total syntheses of natural products that include bromopyrrole alkaloids nagelamide A, D and agelastatin D as...
This dissertation describes the racemic and enantioselective synthesis cavicularin. Cavicularin is a macrocyclic bisbibenzyls family member natural product. It has been an attractive synthetic target due to its intriguing structure: the macrocyclic core imparts sufficient strain on the system to force one benzene rings to adopt a boat-shaped conformation, out...
Studies towards the total synthesis of (+)-Phomactin A (1), D (6), and G (9), fungal metabolites with unique molecular architecture and pronounced biological activity, are described. These studies resulted in the synthesis of advanced intermediates 354 and 356, which contain all of the carbon atoms of 1, 6 and 9....