Compulsive hoarders: how do they differ from individuals with obsessive compulsive disorder?

Hoarding has been considered a subtype of obsessive-compulsive disorder (OCD). Planned revisions to the diagnostic criteria propose that hoarding form a separate diagnosis in a larger category of obsessive compulsive related disorders. To date, there have been few direct comparisons between hoarding and those with other symptoms of OCD. This study builds on work that suggests compulsive hoarding, while similar to OCD, comprises a clinically distinct condition. Three groups were compared: those with OCD without compulsive hoarding symptoms (n=102), those with compulsive hoarding but not OCD (n=21), and individuals who satisfied both criteria (n=25). The groups were compared on obsessionality, compulsivity, overvalued ideas, depression, and anxiety. The two hoarding groups were also compared on hoarding symptoms and savings cognitions. Results indicated that the hoarding-only group reported fewer symptoms than both OCD groups, including fewer obsessions and compulsions and lower depression. Both hoarding groups showed significantly higher overvalued ideas when compared to the OCD-only group. These results suggest that hoarders experience less subjective distress than those with OCD, yet have greater difficulty in challenging dysfunctional cognitions associated with the presenting condition. These findings suggest that individuals with hoarding, whether with or without OCD, will show greater difficulty engaging in cognitive-behavioral interventions.

Copper-facilitated Suzuki reactions: application to 2-heterocyclic boronates.

The palladium-catalyzed Suzuki-Miyaura reaction has been utilized as one of the most powerful methods for C-C bond formation. However, Suzuki reactions of electron-deficient 2-heterocyclic boronates generally give low conversions and remain challenging. The successful copper(I) facilitated Suzuki coupling of 2-heterocyclic boronates that is broad in scope is reported. Use of this methodology affords greatly enhanced yields of these notoriously difficult couplings. Furthermore, mechanistic investigations suggest a possible role of copper in the catalytic cycle.

Practical synthesis of a neuropeptide Y antagonist via stereoselective addition to a ketene.

[Reaction: see text]. The synthesis of neuropeptide Y antagonist 1, currently under clinical investigation for the treatment of obesity, is described. The convergent synthesis from trans-spirolactone carboxylic acid intermediate 2a and aminopyrazole 3 is predicated on a stereoselective route to the former. The coupling reaction of ethyl 4-oxocyclohexanecarboxylate (10a) with lithiated isonicotinamide 11 was investigated in detail, but even optimized conditions only provided a 45:55 ratio of trans:cis isomers (12a:12b). While selective crystallization schemes were developed to isolate the thermodynamically less stable trans isomer 2a, improved stereocontrol was subsequentially achieved by the application of ketene chemistry. The ketene formation and quench was investigated under a variety of conditions aimed at maximizing the trans:cis ratio. Reacting a mixture of carboxylic acids 2a and 2b with POCl3 in THF, followed by concomitant addition of tert-butyl alcohol in the presence of TMEDA at 35 degrees C provided a 4:1 ratio of trans:cis tert-butyl esters (18a:18b) via in situ ketene formation. Ester hydrolysis, followed by selective crystallization of undesired 2b as the HCl salt, led to isolation of 2a in 47% overall yield. Aminopyrazole intermediate 3 was synthesized via the condensation reaction of 2-fluorophenylhydrazine hydrochloride (4a) with acrylonitrile derivative 5 in 65-70% yield. Coupling of advanced intermediates 2a and 3b via activation with thionyl chloride gave a 92% yield of 1.

Ligand-free palladium-catalyzed cyanation of aryl halides.

[reaction: see text] A practical, ligand-free cyanation of aryl bromides that utilizes as little as 0.1 mol % Pd(OAc)(2) in combination with a nontoxic cyanide source, M(4)[Fe(CN)(6)] (M = K, Na), is described. The reactions are performed in DMAC at 120 degrees C and provide the corresponding aryl nitrile in 83-96% yield, typically in less than 5 h. TON values of up to 7100 were attained.

Methods for the synthesis of 5,6,7,8-tetrahydro-1,8-naphthyridine fragments for alphaVbeta3 integrin antagonists.

The preparation of 3-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)propan-1-amine 2a and 3-[(7R)-7-methyl-5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl]propan-1-amine 2b, key intermediates in the synthesis of alpha(V)beta(3) antagonists, is described. The syntheses rely on the efficient double Sonogashira reactions of 2,5-dibromopyridine 3 with acetylenic alcohols 4a/4b and protected propargylamines 10a-e followed by Chichibabin cyclizations of 3,3'-pyridine-2,5-diyldipropan-1-amines 9a/9b.

Crystallization-induced diastereoselection: asymmetric synthesis of substance P inhibitors.

A novel three-component condensation followed by a crystallization-induced asymmetric transformation is used to build this key substance P inhibitor intermediate in a short synthetic sequence.