The sea lamprey is an ancient, parasitic fish that invaded the Great Lakes a century ago, where it triggered the collapse of many fisheries. Like many fishes, this species relies on chemical cues to mediate key aspects of its life, including migration and reproduction. Here we report the discovery of a multicomponent steroidal pheromone that is released by stream-dwelling larval lamprey and guides adults to spawning streams. We isolated three compounds with pheromonal activity (in submilligram quantities from 8,000 l of larval holding water) and deduced their structures. The most important compound contains an unprecedented 1-(3-aminopropyl)pyrrolidin-2-one subunit and is related to squalamine, an antibiotic produced by sharks. We verified its structure by chemical synthesis; it attracts adult lamprey at very low (subpicomolar) concentrations. The second component is another new sulfated steroid and the third is petromyzonol sulfate, a known lamprey-specific bile acid derivative. This mixture is the first migratory pheromone identified in a vertebrate and is being investigated for use in lamprey control.

Host-[2]rotaxanes, containing a diarginine-derivatized dibenzo-24-crown-8 (DB24C8) ether as the ring and a cyclophane pocket or an aromatic cleft as one blocking group, are cell transport agents. These hosts strongly associate with a variety of amino acids, dipeptides, and fluorophores in water (1 mM phosphate buffer, pH 7.0), DMSO, and a 75/25 (v/v) buffer to DMSO solution. All peptidic guests in all solvent systems have association constants (K(A)'s) in the range of 1 x 10(4) to 5 x 10(4) M(-)(1), whereas the K(A) range for the fluorophores is 1 x 10(4) to 9 x 10(5) M(-)(1). Association constants for the cyclophane itself, cyclophane 3, are smaller. These values are in the 1 x 10(3) to 5 x 10(3) M(-)(1) range, which shows that the rotaxane architecture is advantageous for guest binding. Cyclophane-[2]rotaxane 1 efficiently transports fluorescein and a fluorescein-protein kinase C (PKC) inhibitor into eukaryotic COS-7 cells, including the nucleus. Interestingly, cleft-[2]rotaxane 2 does not transport fluorescein as efficiently, even though the results from the fluorescence assays show that both [2]rotaxanes bind fluorescein with the same ability.

1 H and 13 C NMR chemical shifts were measured for a set of six isomers-the cis and trans 2-, 3-, and 4-methylcyclohexanols. 1 H and 13 C NMR chemical shifts were computed at the B3LYP, WP04, WC04, and PBE1 density functional levels for the same compounds, taking into account the Boltzmann distribution among conformational isomers (chair-chair forms and hydroxyl rotamers). The experimental versus computed chemical shift values for proton and carbon were compared and evaluated (using linear correlation (r 2 ), total absolute error (jDdj T ), and mean unsigned error (MUE) criteria) with respect to the relative ability of each method to distinguish between cis and trans stereoisomers for each of the three constitutional isomers. For 13 C shift data, results from the B3LYP and PBE1 density functionals were not sufficiently accurate to distinguish all three pairs of stereoisomers, while results using the WC04 functional did do so. For 1 H shift data, each of the WP04, B3LYP, and PBE1 methods was sufficiently accurate to make the proper stereochemical distinction for each of the three pairs. Applying a linear correction to the computed data improved both the absolute accuracy and the degree of discrimination for most of the methods. The nature of the cavity definition used for continuum solvation had little effect. Overall, use of proton chemical shift data was more discriminating than use of carbon data.

A synthesis of the structurally fascinating fungal metabolite UCS1025A (1) was accomplished. It features a likely biomimetic approach to the octalin subunit via an intramolecular Diels-Alder (IMDA) reaction of a putative triene precursor (2), preceded by an efficient construction of the bisheteratriquinane subunit within that compound. Specifically, an intramolecular silyl triflate-induced cyclization of an in situ-generated silyl ketene acetal onto an imide carbonyl group (e.g., 7 to 8) was developed. The IMDA relative reactivities of a family of valence bond isomers, each differing in the precise nature of the dienophilic subunit, were determined. Under biologically relevant conditions (D2O, pH 7.2 buffer, ca. 25 degrees C), triene 2, via its lactone ring-opened congener, underwent very fast (t1/2 = 10 min) conversion to the ring-opened forms of 1 (i.e., 5a) and the tetraepimeric, alternative endo-adduct, 3 [i.e., (tetraepi)-5a].

[Structure: see text] Trialkylsilyl triflates effect cyclization of ester-imides such as 2 to produce adducts such as 4a. Trapping of the in situ generated, nucleophilic ketene acetal (cf. 5a) is a key aspect of the transformation. A range of substrates amenable to this operationally simple reaction is reported. In many instances the levels of diastereoselectivity are very high. Mechanistic points are inferred from spectroscopic observations.