Alan W. Schwabacher

Mechanism of cholesterol reduction to coprostanol by Eubacterium coprostanoligenes ATCC 51222

The mechanism of reduction of cholesterol to coprostanol by Eubacterium coprostanoligenes ATCC 51222 was studied by incubating the bacterium with a mixture of alpha- and beta-isomers of [4-3H,4-14C]cholesterol. Coprostanol, isolated after incubation of [4-3H,4-14C]cholesterol in a growth medium under anaerobic conditions, retained 97% of the tritium originally present in cholesterol. The majority of this tritium (64%), however, was in the C-6 position in coprostanol, which showed that the conversion of cholesterol into coprostanol by E. coprostanoligenes involved the intermediate formation of 4-cholesten-3-one followed by the reduction of the latter to coprostanol. In resting cell assays in which washed bacterial cells were incubated with micellar cholesterol in phosphate buffer at 37 degrees C, both 4-cholesten-3-one and coprostanone were produced in addition to coprostanol. Furthermore, 5-cholesten-3-one, 4-cholesten-3-one, and coprostanone were converted efficiently to coprostanol by E. coprostanoligenes. These results support the hypothesis that the major pathway for reduction of cholesterol by E. coprostanoligenes involves the intermediate formation of 4-cholesten-3-one followed by reduction of the latter to coprostanol through coprostanone as an intermediate.

Improved preparation of phosphinate esters for palladium-catalyzed cross-coupling

Abstract The reaction between phosphinic acid and trimethyl orthoformate to yield methyl phosphinate shows a pronounced solvent dependence. Conditions are defined to improve ester purity. t-Butyl phosphinate is also prepared cleanly, and its palladium-catalyzed reaction with aryl iodide is reported.

Preparation of peptide thioacids using the Kaiser oxime resin

Abstract Peptide C-terminal thioacids are prepared with protecting groups intact by cleavage of peptides from Kaisers oxime ester resin by treatment with hexamethyldisilathiane / tetrabutylammonium flouride. Such thioacids are useful for peptide fragment couplings.

Base-Mediated Stereospecific Synthesis of Aryloxy and Amino substituted Ethyl Acrylates

The stereospecific synthesis of aryloxy and amino substituted E- and Z-ethyl-3-acrylates is of interest because of their potential in the polymer industry and in medicinal chemistry. During work on a copper-catalyzed cross-coupling reaction of ethyl (E)- and (Z)-3-iodoacrylates with phenols and N-heterocycles, we discovered a very simple (nonmetallic) method for the stereospecific synthesis of aryloxy and amino substituted acrylates. To study this long-standing problem on the stereoselectivity of aryloxy and amino substituted acrylates, a series of O- and N-substituted nucleophiles was allowed to react with ethyl (E)- and (Z)-3-iodoacrylates. Screening of different bases indicated that DABCO (1,4-diazabicyclo[2.2.2]octane) afforded successful conversion of ethyl (E)- and (Z)-3-iodoacrylates into aryloxy and amino substituted ethyl acrylates in a stereospecific manner. Herein are the details of this DABCO-mediated stereospecific synthesis of aryloxy and amino substituted E- or Z-acrylates.

Highly selective acylations using a biomimetic strategy

Abstract Rapid, high yield acylation of thiol-bearing amines by one equivalent of thioacid may be carried out at 1 mM in the presence of large excesses of other primary amines. Silver ion, known to activate thoacids toward nucleophilic attack, simultaneously also serves as a binding site to deliver a thiol-tethered amine. An interesting dependence of yields and selectivity on [Ag+] was found, as well as a significant effect of chloride.

Total Synthesis of Macrocarpines D and E via an Enolate-Driven Copper-Mediated Cross-Coupling Process: Replacement of Catalytic Palladium with Copper Iodide

An enolate driven copper-mediated cross-coupling process enabled cheaper and greener access to the key pentacyclic intermediates required for the enantiospecific total synthesis of a number of C-19 methyl substituted sarpagine/macroline indole alkaloids. Replacement of palladium (60-68%) with copper iodide (82-89%) resulted in much higher yields. The formation of an unusual 7-membered cross-coupling product was completely inhibited by using TEMPO as a radical scavenger. Further functionalization led to the first enantiospecific total synthesis of macrocarpines D and E.

Synthesis of3H- polyethylene and its use for fate studies on degradable plastics

Determining the fate of xenobiotic materials in the environment can be aided by the use of radioactive isotope technology. Previous research on the degradation of polymers such as polyethylene (PE) was aided by the utilization of radiotracers. In order to study the environmental fate of degradable (PE/starch) plastics, we synthesized3H-labeled PE. Results of soil incubation studies indicate that only minimal degradation of the PE component, as indicated by the production of water-soluble metabolites, occurred during 2 years of incubation in soil. Despite the minimal degradation, the3H label did not allow for detection of the degradation products. In addition, the3H-PE was particularly useful for tracing the fate of degradable plastics after consumption by terrestrial isopods. The detection of aqueous-soluble radioactivity in isopod frass was used to indicate degradation of the plastic film.