Christopher J. Nichols

Highly stereoselective synthesis of trans,trans-4-aryl-2,3-oxetanedimethanols: Preparation of oxetanocin a analogues

A short (5-step) synthesis of the oxetanocin A analogues 12a and 12b has been accomplished, with very good stereoselectivity in the key iodocyclization step.

Two Invariant Tryptophans on the α1 Subunit Define Domains Necessary for GABAA Receptor Assembly

Two invariant tryptophan residues on the N-terminal extracellular region of the rat α1 subunit, Trp-69 and Trp-94, are critical for the assembly of the GABAA(γ-aminobutyric acid, type A) receptor into a pentamer. These tryptophans are common not only to all GABAA receptor subunits, but also to all ligand-gated ion channel subunits. Converting each Trp residue to Phe and Gly by site-directed mutagenesis allowed us to study the role of these invariant tryptophan residues. Mutant α1 subunits, coexpressed with β2 subunits in baculovirus-infected Sf9 cells, displayed high affinity binding to [3H]muscimol, a GABA site ligand, but no binding to [35S]t-butyl bicyclophosphorothionate, a ligand for the receptor-associated ion channel. Neither [3H]muscimol binding to intact cells nor immunostaining of nonpermeabilized cells gave evidence of surface expression of the receptor. When expressed with β2 and γ2 polypeptides, the mutant α1 polypeptides did not form [3H]flunitrazepam binding sites though wild-type α1 polypeptides did. The distribution of the mutant receptors on sucrose gradients suggests that the effects on ligand binding result from the inability of the mutant α1 subunits to form pentamers. We conclude that Trp-69 and Trp-94 participate in the formation of the interface between α and β subunits, but not of the GABA binding site.

A de novo synthesis of ethyl 2-deoxy-l-ribosides☆

Abstract A short (7-step) and efficient synthesis of several derivatives of 2-deoxy- l -ribose 1 , e.g., the ethyl ribosides, 2abc , has been accomplished from achiral precursors.

Synthesis of a Model Compound of Corydendramine A via a Julia Coupling

Abstract The synthesis of the tetraenylpiperidine 12, which has the same core structure as the natural product corydendramine A, has been completed in eight steps starting from 2-piperidinemethanol 3 and trans,trans-2,6-nonadienal 6. The key step of the synthesis was a Julia coupling of sulfone (10) with aldehyde (5) to form a conjugated triene.

The formation of 7-oxabicyclo[4.2.0]octanes and 6-oxabicyclo[3.2.1]octanes via cationic iodocyclization

Abstract Several 2-cyclohexenemethanol derivatives were subjected to cationic iodocyclization. Two product types were formed: the fused 7-oxabicyclo[4.2.0]octane, and the bridged 6-oxabicyclo[3.2.1]octane. The degree of substitution in the alkenol determined the ratio of the products, with aromatic substituents leading to the formation of the fused system as the major product.