Fluorescent profiling of natural product producers

The identification of natural product producer organisms remains a problem for both isolation and natural product classification. A concise screen is developed through fluorescent modification of a set of natural products that offer a common activity. Through real-time multicolor microscopy, the processing, storage, and effects of a natural product are rapidly screened at the level of the strain and individual organism.     

Bridging the synthetic and biopolymer worlds with peptide-drug conjugates

Roberts and Li break the standard library mold by generating hybrid libraries of small molecules tethered to peptides. Hybrid libraries harness larger chemical and structural diversities and thus represent a new frontier in lead drug discovery.     

Identifying bryostatins and potential precursors from the bryozoan Bugula neritina

The bryozoan species Bugula neritina contains the anticancer agent bryostatin. Bryostatin has been extracted from these sessile marine invertebrates since the late 1960s from the Gulf of California, Gulf of Mexico, as well as various locations on the eastern and western rims of the Pacific Ocean. In this work we are focusing on animals harvested in the Gulf of Mexico near Alligator Point (Florida). Using Inductively Coupled Plasma-Mass Spectrometry (ICP-MS) we measure the concentration of 70 elements in B. neritina, a sea squirt, and the sediment from the point of harvesting. This data has helped us generate an extraction process for marine natural products. Combining UV/VIS absorbance measurements with Matrix Assisted Laser Desorption Ionization-Time of Flight-Mass Spectrometer (MALDI-TOF-MS), we demonstrated that the specific form of bryostatin extracted is a function of the solvent. A 9.4T Fourier Transform-Ion Cyclotron Resonance (FT-ICR) mass spectrometer, whose sensitivity, mass accuracy, and resolving power allowed the exact empirical formulas of potential precursors of bryostatin to be identified, was employed. Finally we examine extracts of 14 marine species of the Gulf of Mexico, from the sand trout (Cynoscion arenarius) to chicken liver sponge (Chrondrilla nucula), all recently collected, which had shown some medicinal activity thirty years ago in a National Cancer Institute study. By the MALDI-TOF-MS, we were able to identify mass spectral features that correspond to different variations of the basic bryostatin structure, which raises the question if the bryozoans are the original source of bryostatin.     

Stereo- and regioselectivity in iodo diol formation from acyclic allylic alcohols

Reaction of electrophiles with a variety of acyclic allylic alcohols was investigated. Both aqueous iodine and acetylhypoiodite convert certain alkenols into iodo diols and acetoxy iodo alcohols, respectively, with regio- and stereoselectivities as high as 99%. Protection of the alcohol group lowers the selectivity only slightly. Structural factors that control the regioselectivity ofiodohydrin formation in these substrates have been delineated. Some of the iodo diols have been deiodinated, illustrating a simple two step procedure for converting allylic alcohols into threo-1,3-diols.     

Stereoselective iodolactonization of acyclic unsaturated 3-hydroxyacids

A stereoselective method for preparing 3-hydroxy-4-alkyl-γ-lactones is reported. iodolactonization of 3-hydroxy-4-alkenoic acids produces predominantly the thermodynamically less stable 3,4-cis products, which undergo methanolysis to $\text{threo}$-epoxyalcohols.