Studies on analogs of DAMASCENOLIDETM: Part 3. Synthesis and odor evaluation of dimethylated, cyclopropanated, and other analogs of DAMASCENOLIDETM

ABSTRACT DAMASCENOLIDETM [1, 4-(4-methylpent-3-en-1-yl)furan-2(5H)-one], which has a citrus-like odor, is an important aroma component of roses. We have previously reported on the synthesis and odor evaluation of 24 analogs of 1 as part of our new aroma compound developing project. To accumulate more information on structure–odor relationships, 10 more promising analogs such as dimethylated and cyclopropanated analogs were synthesized and subjected to odor evaluation. As a result, it was found that dimethylation of the furanone ring affected the odor. It was also found that cyclopropanation of 1 affected the odor, whereas cyclopropanation of the double bond isomer of 1 did not significantly affect the odor. The effects on the odor caused by ring size expansion and replacement of the side chain were also investigated.

Recombinant production and structure-function study of ts1 toxin from the Brazilian scorpion Tityus serrulatus

This work introduces an effective bacterial system for the production of β-toxin Ts1, the main component of the Brazilian scorpion Tityus serrulatus venom. Recombinant toxin and its 15N-labeled analogue are obtained by direct expression of the synthetic gene in Escherichia coli, with subsequent folding from the inclusion bodies. NMR spectroscopy data assert that the recombinant toxin is structured in aqueous solution and is composed of a significant fraction of β-structure. Moreover, the formation of a stable Ts1 disulfide-bond isomer of a disordered structure is observed during folding; recombinant Ts1 blocks Na+ current through NaV1.5 channels, without affecting the processes of activation and inactivation. Simultaneously, the effect upon NaV1.4 channels is associated with a shift of the activation curve toward the more negative membrane potentials.

Preparation of Three Impurities in Cefoxitin

Three known impurities of cefoxitin have been prepared and characterised. One is a double-bond isomer of cefoxitin, Δ3-cefoxitin, which was easily prepared by base-catalysed isomerisation of cefoxitin. The second is a side-chain methoxylated derivative, methoxycefoxitin, which required a four-step synthesis from cephalothin. The last impurity is a lactone lacking the carbamyl grouping in cefoxitin, cefoxitin lactone, which was also prepared in four steps from cephalothin. The accessibility of these three impurities and methods for their analysis could be important for quality control in the manufacture of cefoxitin.

Synthetic Studies Concerning the Crinine Alkaloid Haemultine

The racemic form, (±)-1, of the structure originally assigned to the crinine alkaloid haemultine has been prepared for the first time. A key step involved the conversion of compound (±)-4 into the isomeric cis-C3a-arylhexahydroindole (±)-3 using a Pd0-catalysed intramolecular Alder-ene reaction. The amino-alcohol (±)-2 derived from the latter compound reacted with paraformaldehyde in the presence of trifluoroacetic acid to give, via a Pictet–Spengler reaction, the target (±)-1. The diastereoisomeric Mosher esters 15 and 16 obtained by coupling the racemate (±)-1 with the R-form, 14, of the Mosher acid could be separated chromatographically and then reductively cleaved to give the enantiomerically pure compounds (+)-1 and (–)-1, respectively. The physical and spectroscopic data derived from the former enantiomer are consistent with the proposition that the title natural product is, in fact, a mixture of (+)-1 and its Δ2,3-double bond isomer.