Nicholas Alex Saccomano

The total synthesis of argiotoxins 636, 659 and 673

Practical syntheses of three polyamine spider toxins isolated from the venom of Argiope aurantia are described.

Synthesis of neurotoxic nephila spider venoms: NSTX-3 and JSTX-3

Abstract Efficient and practical synthetic routes to the polyamine spider venom principles, NSTX-3 and JSTX-3 are described.

Chapter 30. Polyamine Spider Toxins: Unique Pharmacological Tools

Publisher Summary The polyamine toxins, obtained from the venom of a variety of orb-weaver spiders are rapidly emerging as unique tools for understanding excitatory amino acid (EM) transmission and related pharmacology or physiology. In this chapter, the chemistry and pharmacology of Araneidae polyamine spider venom toxins is reviewed and a brief discussion of the venom from the funnel-web spider is also included. The chemistry involved in the preparation of many of the naturally occurring polyamines has been discussed in the chapter. Polyamine spider venoms have highly polar hydroxyaryl and amino acid residues. Interest in the polyamine spider toxins is a result of the observation that these molecules affect those synapses, at which an excitatory amino acid (EAA) is the neurotransmitter. Compounds that affect EAA function, particularly those that antagonize the action of such transmitters, are therefore of considerable agricultural (insect control) and therapeutic interest. Blockade of neuromuscular transmission in invertebrates by polyamin spider toxins reveals their glutamate antagonist activity. Polyamine spider venoms also act on glutaminergic synapses in vertebrate systems. Partially purified JSTX blocks the responses of CA1 pyramidal neurons in rat hippocampus both to stimulation of the appropriate afferent neurons and to direct the application of glutamate. A variety of venoms have been screened for their ability to block synaptic transmission at glutaminergic synapses in the chick cochlear nucleus. A number of toxins from the funnel-web spider Agelenopsis aperta paralyze insects. These toxins contain low molecular weight acylpolyamine constituents, at least six amino acid residue peptides, and several larger polypeptides. Two classes of toxins from Agelenopsis aperta venom that block the transmission in the chick cochlear nucleus assay have also been discussed in the chapter. The results of these studies suggest that considerable structural and functional diversity exists within the polyamine toxin class and that these compounds differ significantly from previously-known classes of EAA and calcium antagonists.

Lipase mediated optical resolution of bicyclic secondary carbinols

Abstract The optical resolution (±) -endo-bicyclo[2.2.1] heptan-2.ol and (±) bicyclo [2.2.2] octan-2-ol proceeds by porcine lipase catalyzed transesterification under anhydrous conditions.

Chapter 4. Diversity of Neuronal Calcium Channels

Publisher Summary One of the distinguishing characteristics of neurons is their excitability due to the presence of voltage-dependent ion-channel proteins in neuronal membranes. Ion channels, selectively permeable to Ca2+, are abundant in the neuronal tissue. There is an abundance of voltage-dependent Ca2+ channels and diversity of neuronal Ca2+ channels. This chapter discusses the work that explores the characteristics of neuronal Ca2+ channels and presents the current state of knowledge of Ca2+ channels in central neurons. The classification of neuronal Ca2+ channels is based on electrophysiological recordings, using patch-clamp techniques, from peripheral neurons of either whole cell ionic currents or single channels. Calcium channels, in both central and peripheral neurons, have been divided using these techniques into two categories based on the level of membrane depolarization required for activation—that is, low-voltage-activated (LVA) and high-voltage-activated (HVA) channels. The focus is on the classification of voltage-dependent Ca2+ channels where high-voltage- and low-voltage-activated Ca2+ channels have been differentiated based on the properties such as channel class, depolarization required for activation, and inactivation kinetics. The chapter also discusses the functions of neuronal Ca2+ channels, diversity of calcium channels, and molecular properties of voltage-dependent Ca2+ channels.

A novel rearrangement forming 4,5,6,11-tetra-hydrobenzo[6,7]cycloocta[1,2-b]thiophen-6,11-imines

Exposure of the spirocyclic isoindolines 9 and 16 and the spirocyclic ether 23 to HBr gas in methylene chloride at 0°C leads to the formation of the bridged heterocycles 10, 17, and 24 respectively. These novel rearrangements probably occur via retro-Mannich fragmentation and subsequent intramolecular Mannich reaction on the thiophene ring.

Enzymatic resolution of endo-bicyclo (2.2.1)heptan-2-ol

Abstract Optically active endo-bicyclo[4.1.0]heptan-2-ols compounds were prepared by lipase-catalyzed transesterifications with the racemic alcohols. High enantioselectivities and reaction rates were observed using the lipase from Candida antarctica.