Addition of an alkyl substituted triaminopyrimidine, TAP, to a solution of porphyrin 2 bearing two rigidly attached complementary hydrogen bonding moieties of the uracil type, leads to the self-assembly of a bisporphyrin supramolecular cage structure 1 from the syn rotamer and probably a zig-zag strand from the anti rotamer.

The development of a unified synthetic strategy for the indole diterpene tremorgens has led to the first total synthesis of (+)-paspalicine (2) and (+)-paspalinhe (3). in 22 and 23 steps, respectively. The cornerstone of the approach is the intermediacy of (-)-2o, this proposed common precursor to the simple indole diterpenes was generated in nine steps from (+)-Wieland-Miescher ketone (26) in our earlier synthesis of (-)-paspaline (1). Key transformations include installation of the indole unit via the Gassman protocol, alkylation of the thermodynamic anion of dimethylhydrazone 74 with epoxide (-)-24, and RhC13-promoted isomerization of the P,y-unsaturated ketone in (+)-81 to afford (+)-paspalicine (2). (+)-Paspalinine (3) in turn was secured via SeO, oxidation of 2, a particularly noteworthy result given the importance of the C(4b) hydroxyl group for tremorgenic activity. MM2 calculations revealed that 2 and 3 embody the less stable relative configuration of the F-and G-ring bicyclic ketal moiety.The indole diterpenes comprise an important class of architecturally complex, biologically significant fungal metabolites ( Figure 1). All but the simplest examples (i.e., 1 and 2) induce tremors in animals,' and recent work has revealed potent insecticidal activity against common crop pests.2 Paspaline (1),3 paspalicine (2),3 paspalinine (3),1b,4 and the paspalitrems (6-8)1b,5 derive from the fungus Claviceps paspali; 3 and 6-8 cause the Paspalum staggers, a livestock syndrome associated with feeding on ergotized Paspalum grass. Ib Whereas dehydroxypaxilline6 (4) has not yet been subjected to biological screening, the C(4b)hydroxy congener paxilline (5) acts both as a tremorgen and an inse~ticide.~~~.'.~ Paxilline also appears to serve as a pivotal biosynthetic precursor of more complex tremorgens including the penitrems (10-15),8 janthitrems (17-19),9 and lolitrem B (16).1a.10Pursuant to our long-standing interest in the development of unified synthetic strategies, we have undertaken a program aimed initially at construction of the simple indole diterpenes-paspaline ~~~~~ ~ (1) (a) Galiagher, R. T.; White, E. P.; Mortimer, P. H. N. Z . Vet. J . 1981, 29, 189. (b) Cole, R. J.; Dorner, J. W.; Lansden, J. A,; Cox, R. H.; Pape, C.; Cunfer, B.; Nicholson, S. S.; Bedell, D. M.

G protein-coupled adenosine receptors are promising therapeutic targets for a wide range of neuropathological conditions, including Parkinson's disease (PD). However, the ubiquity of adenosine receptors and the ultimate lack of selectivity of certain adenosine-based drugs have frequently diminished their therapeutic use. Photopharmacology is a novel approach that allows the spatiotemporal control of receptor function, thus circumventing some of these limitations. Here, we aimed to develop a light-sensitive caged adenosine A receptor (AR) antagonist to photocontrol movement disorders. We synthesized MRS7145 by blocking with coumarin the 5-amino position of the selective AR antagonist SCH442416, which could be photoreleased upon violet light illumination (405 nm). First, the light-dependent pharmacological profile of MRS7145 was determined in AR-expressing cells. Upon photoactivation, MRS7145 precluded AR ligand binding and agonist-induced cAMP accumulation. Next, the ability of MRS7145 to block AR in a light-dependent manner was assessed in vivo. To this end, AR antagonist-mediated locomotor activity potentiation was evaluated in brain (striatum) fiber-optic implanted mice. Upon irradiation (405 nm) of the dorsal striatum, MRS7145 induced significant hyperlocomotion and counteracted haloperidol-induced catalepsy and pilocarpine-induced tremor. Finally, its efficacy in reversing motor impairment was evaluated in a PD animal model, namely the hemiparkinsonian 6-hydroxydopamine (6-OHDA)-lesioned mouse. Photo-activated MRS7145 was able to potentiate the number of contralateral rotations induced by L-3,4-dihydroxyphenylalanine (l-DOPA). Overall, MRS7145 is a new light-operated AR antagonist with potential utility to manage movement disorders, including PD.

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meso-Tetraalkylporphyrins were synthesized in good yields from aliphatic aldehydes and pyrrole by using the clay, montmorillonite K10. The nanometer size porous structures of K10 provide suitable reaction media for polymerization-cyclization condensations of aldehyde and pyrrole.

Examples are presented in which the stereochemical course of the Claisen rearrangement of allylic glycolates is controlled by a chiral substituent appended to the glycolate hydroxyl (eq 1).Sir: Recent studies1,2 have focused on synthetic and mechanistic aspects of the highly diastereoselective enolate Claisen rearrangment3 of acyclic -alkoxy esters. Herein

C-Glycosyl amino acids represent stable mimics of monomeric units within natural O-linked glycoproteins. Olefin cross-metathesis has been used to provide alkene precursors for a mercury(II)-mediated cyclization, yielding alpha-C-glucosyl serine and alanine.

[formula: see text] The stereoselective preparation of C-linked D-gluco- and D-galactopyranosyl L-serines in their alpha and beta forms is herein reported. The syntheses require the conversion of the allyl C-glycopyranosides into their iodoethyl derivatives, which then undergo substitution with the Williams' chiral glycine enolate equivalent. Deprotection and acetylation affords Boc-protected amino acids for peptide synthesis.