Jeffrey J. Rohde

The application of the formyl CH--O hydrogen bond postulate to the understanding of enantioselective reactions involving chiral boron lewis acids and aldehydes

Abstract A number of noteworthy enantioselective reactions involving a variety of chiral boron Lewis acids and aldehydes can be rationalized in terms of the occurrence of formyl CH--O hydrogen bonds in the transition states and the additional three-dimensional organization which they provide.

A HYPOTHESIS FOR CONFORMATIONAL RESTRICTION IN COMPLEXES OF FORMYL COMPOUNDS WITH BORON LEWIS ACIDS. EXPERIMENTAL EVIDENCE FOR FORMYL CH--O AND CH--F HYDROGEN BONDS

X-ray crystallographic analysis of six complexes of formyl compounds with BF or BO containing boron Lewis acids reveals in every case a geometric preference for a conformation in which the formyl group and the BF or BO bond are coplanar, or nearly so.

Acute Inhibition of 11β-Hydroxysteroid Dehydrogenase Type-1 Improves Memory in Rodent Models of Cognition

Mounting evidence suggests excessive glucocorticoid activity may contribute to Alzheimers disease (AD) and age-associated memory impairment. 11β-hydroxysteroid dehydrogenase type-1 (HSD1) regulates conversion of glucocorticoids from inactive to active forms. HSD1 knock-out mice have improved cognition, and the nonselective inhibitor carbenoxolone improved verbal memory in elderly men. Together, these data suggest that HSD1 inhibition may be a potential therapy for cognitive deficits, such as those associated with AD. To investigate this, we characterized two novel and selective HSD1 inhibitors, A-918446 and A-801195. Learning, memory consolidation, and recall were evaluated in mouse 24 h inhibitory avoidance. Inhibition of brain cortisol production and phosphorylation of cAMP response element-binding protein (CREB), a transcription factor involved in cognition, were also examined. Rats were tested in a short-term memory model, social recognition, and in a separate group cortical and hippocampal acetylcholine release was measured via in vivo microdialysis. Acute treatment with A-801195 (10–30 mg/kg) or A-918446 (3–30 mg/kg) inhibited cortisol production in the ex vivo assay by ∼35–90%. Acute treatment with A-918446 improved memory consolidation and recall in inhibitory avoidance and increased CREB phosphorylation in the cingulate cortex. Acute treatment with A-801195 significantly improved short-term memory in rat social recognition that was not likely due to alterations of the cholinergic system, as acetylcholine release was not increased in a separate set of rats. These studies suggest that selective HSD1 inhibitors work through a novel, noncholinergic mechanism to facilitate cognitive processing.

An efficient one-pot synthesis of substituted 2-arylbenzo[b]thiophene derivatives

Abstract This communication describes an efficient one-pot procedure for the synthesis of 2-arylbenzo[ b ]thiophene derivatives via reaction of o -halo or nitro aryl carbonyl compounds with benzyl mercaptans in the presence of an excess of anhydrous K 2 CO 3 at elevated temperature.