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...
The first part of this manuscript is about the total synthesis of the Arundo donax bis(indole) natural products. The A. donax alkaloids were prepared using the first example of an ynindole Diels–Alder reaction. Each were then separated, isolated, and determined to have stable enantiomeric conformations at room temperature (Chen, J.;...
Nitroaromatic compounds have important chemical applications and can be found in nature as pollution sources. Synthetic nitroaromatic compounds have been used in a variety of materials including explosives, pharmaceuticals, dyes, plastics, and pesticides. These compounds can find their way into the environment through normal or improper disposal methods.
Poly-aromatic compounds...
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...
Coibamide A is a highly methylated cyclic depsipeptide isolated from Panamanian marine filamentous cyanobacteria as part of an International Cooperative Biodiversity Groups (ICBG) program based in Panama. This structurally unique agent exhibits potent cancer cell toxicity with an unprecedented selectivity profile in the National Cancer Institute (NCI) 60 cell line...
Natural products (a.k.a. secondary metabolites) are produced by living organisms that are not essential for their growth, development, or reproduction, but may play a role in their survival or adaptability in nature. Many secondary metabolites isolated from plants and microbes have found use as molecular probes, drug leads, or medicine...
Pharmaceuticals, molecular catalysts, and secondary metabolites often contain nitrogen. The problems faced synthesizing compounds which contain nitrogen was because of the Lewis base reactivity of nitrogen lone pairs, and the acidic protons of some nitrogenous functional groups. We developed two methods for the synthesis of nitrogeous compounds. Additionally, we successfully...
Historically, the difficulty of obtaining pure cultures of abundant marine
microbial plankton has an obstacle to reconstructing the underlying
mechanisms of biogeochemistry in the ocean. While a number of dominant
marine species from the ocean surface have been cultured, the dominant
microbial plankton of the dark ocean proved far more...
An increased understanding of secondary metabolism in fungi is important for both biological and societal reasons. The ascomycete genus, Tolypocladium, is an ideal system to explore secondary metabolism characterization, ecology, evolution and regulation. The genus produces and has the genomic potential to produce a wide array of metabolites. Paired with...
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)...