The tremendous potential of cyclopropenes and methylene-cyclopropanes as multifunctional reagents in organic syntheses has only been recognized in the last decade. The use of transition metal catalysts allows an effective control of their transformations enabling highly selecitive syntheses ranging from three- to sevenmembered carbocycles. The activities in this field are summarized in this review for the first time with an emphasis on the preparative aspects of this work.

Cyclopropenes and methylenecylopropanes as multifunctional reagents in transition metal catalyzed reactions

Recent developments in tetrazole chemistry. a review

It is textbook knowledge that carboxamides benefit from increased stabilisation of the electrophilic carbonyl carbon when compared to other carbonyl and carboxyl derivatives This results in a considerably reduced reactivity towards nucleophiles Accordingly, a perception has been developed of amides as significantly less useful functional handles than their ester and acid chloride counterparts However, a significant body of research on the selective activation of amides to achieve powerful transformations under mild conditions has emerged over the past decades This review article aims at placing electrophilic amide activation in both a historical context and in that of natural product synthesis, highlighting the synthetic applications and the potential of this approach

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Amide activation: an emerging tool for chemoselective synthesis

Chemical Transformations Induced by Triflic Anhydride

From organosuperbases capable of base-catalyzing organic reactions, through versatile ‘ligand-sets’ for use in coordination chemistry, to fundamental entities in medicinal chemistry, guanidines are amongst the most interesting, attractive, valuable, and versatile organic molecules. Since the discovery of these compounds, synthetic chemists have developed new methodologies that are mainly based on multi-step and stoichiometric reactions. Despite the fact that these methodologies are still being used by the interested scientific and industrial communities, drawbacks such as the poor availability of precursors, low yields, and use and production of undesirable substances highlight the need for safe, simple and efficient syntheses of these entities. This review focuses on the metal-mediated catalytic addition of amines to carbodiimides as an atom-economical alternative to the classical synthesis.

Guanidines: from classical approaches to efficient catalytic syntheses

Routine screening of compounds for inhibition of collagen-induced platelet aggregation in vitro revealed 4,5-bis-(4-methoxyphenyl)-1,2,3-thiadiazole (2) was active and it represents the first example of a 1,2,3-thiadiazole with possible antithrombotic activity. In order to develop a structure-activity relationship for this heterocycle, a number of new 4(5)-mono- and -disubstituted 1,2,3-thiadiazoles were synthesized. These were tested in our screen and a number of additional active compounds were found. The most active compounds (2, 5a, 5b, and 6c) were those in which the heterocycle was substituted with benzene rings possessing para electron-donating groups.

Synthesis and platelet aggregation inhibitory activity of 4,5-bis(substituted)-1,2,3-thiadiazoles

The present invention relates to small molecules according to formula (I) which are potent inhibitors of a α4β1 mediated adhesion to either VCAM or CS-1 and which can be used for treating or preventing α4β1 adhesion mediated conditions in a mammal such as a human.

Inhibitors of alpha-4 beta-1 mediated cell adhesion

Due to the interest in tetrazoles as medicinal agents, a new, mild one-step method for the conversion of amides to tetrazoles employing triphenylphosphine, diethyl azodicarboxylate, and trimethylsilyl azide was recently introduced. An alternate and equally simple method employing trifluoromethanesulfonic anhydride and sodium azide was devised. This method was used to synthesize a series of 1,5-substituted tetrazoles from readily available secondary amides. A 1H-substituted tetrazole was also synthesized by this method from an amide substituted with a cyanoethyl protecting group

The Conversion of Secondary Amides to Tetrazoles with Trifluoromethanesulfonic Anhydride and Sodium Azide

Routine screening of compounds for inhibition of ADP-induced platelet aggregation in vitro revealed that 1,1'-hexamethylenebis[3-cyclohexyl-3-[(cyclohexylimino) (4-morpholinyl) methyl]urea] (1) was active and represented the first example of a bis(acylguanidine) with possible antithrombotic activity. In order to develop a structure-activity relationship for this class of compounds, we synthesized a number of new bis(acylguanidines). These were tested in vitro, and several analogues were also active. Ex vivo testing revealed that compounds 22, 41, 58, and 70-73 were orally active in rats or guinea pigs.

Edward W. Thomas

Papers

Synthesis and platelet aggregation inhibitory activity of 4,5-bis(substituted)-1,2,3-thiadiazoles

Inhibitors of alpha-4 beta-1 mediated cell adhesion

The Conversion of Secondary Amides to Tetrazoles with Trifluoromethanesulfonic Anhydride and Sodium Azide

Synthesis of acylguanidine analogues: inhibitors of ADP-induced platelet aggregation.

Reaction of methylenecyclopropyllithium with electrophiles