Chemistry of pyrrolizines; reactions with cyanogen bromide and trifluoroacetic anhydride

Interaction of the pyrrolizine 3 with cyanogen bromide in a tetrahydrofuran/water mixture affords addition to the enamine double bond with formation of 5 which can be aromatized to 6 by silica gel. Reaction of 6 with cyanogen bromide in the same solvent mixture yields the indoline 8a which structure is proved in a chemical way by conversion of the product into the aldehyde 8d. The different reaction pathway is discussed in terms of steric hindrance by the ester groups. Treatment of 6 with trifluoroacetic anhydride gives the trifluoroacetylated compound 11. Removal of the sterically hindered ester groups in 6, with acetic acid in quinoline at 200°, is accompanied by the simultaneous decarboxylation to yield the pyrrolo[1,2-a]indole 1

Novel applications of the “t-amino effect” in heterocyclic chemistry; synthesis of 5H-pyrrolo- and 1H,6H-pyrido[1,2-a][3,1]benzoxazines

Trifluoroacetylated N,N-dialkylanilines react in refluxing 1-butanol to benzoxazine derivatives via an intramolecular] [1, 5] hydrogen shift and subsequent cyclization of the dipolar intermediate

On the mechanism of the reaction of enamines and dimethyl acetylenedicarboxylate (DMAD) in polar and apolar solvents

[2+2]-Cycloadducts of enamines and DMAD, formed in apolar solvents, isomerize to pyrrolizine derivatives under mild conditions in protic polar solvents like methanol and 1-butanol

Novel applications of the "t-amino effect" in heterocyclic chemistry. Synthesis of a pyrrolo[1,2-a]quinazoline and 5H-pyrrolo[1,2-a][3,1]benzothiazines

1-(1-Pyrrolidinyl)benzenes substituted with an imino- or an in situ generated thiocarbonyl group in the 2-position rearrange upon heating to quinazoline and benzothiazine derivatives, respectively

The madelung synthesis of dihydro-1H-pyrrolo- and tetrahydropyrido[1,2-a]- indoles under mild conditions

Benzeneacetonitriles substituted with lactam moieties in the ortho-position cyclize under the influence of a base, dependent on the ring-size of the lactam function, to dihydropyrrolo-, tetrahydropyrido[1,2-a]indole or dihydro-1-benzazepin derivatives, respectively

Synthesis of 18F-labelled 2-fluoro-1,4-quinones using acetylhypofluorite

The fluorination of 1,4-benzo- and naphthoquinones using [18F]acetylhypofluorite is described. For compounds with electron-donating substituents fair to good radiochemical yields have been reached

Microsomal superoxide anion production and NADPH-oxidation in a series of 22 aziridinylbenzoquinones

Several 2,5-bis(1-aziridinyl)-1,4-benzoquinones (BABQs) can be activated to alkylating species by reduction of the quinone moiety. On the other hand, cytotoxicity of these compounds can be induced by redox cycling. A series of BABQs and their methylated analogues (BMABQs) with different substituents at the 3- and 6-position was synthesized in order to investigate the influence of the substituents on the reduction of the quinone moiety and on the generation of superoxide anion radicals with rat liver microsomes. Superoxide anion production (SAP) ranged from 3.7±0.1 to 742±74 nmoles/min/mg protein with quinone concentrations of 10 nmoles/ml. NADPH-oxidation was measured under the same conditions and it correlated well (r = 0.88, P < 0.001) with SAP. It ranged from 1.4±0.2 to 494±60 nmoles/min/mg protein. SAP for 22 B(M)ABQs showed a good correlation with the summated electronic substituent constant θpara,total (r = 0.86, P < 0.001). It can be concluded that superoxide anion production by 22 B(M)ABQs in rat liver microsomes can be predicted from structural features of the compounds

A realist perspective on the use of research evidence in health policymaking

The achievement of “evidence-informed” policy is an aspiration espoused by policymakers, academics and citizens alike, but governments have faced considerable challenges in pursuit of this ideal. The methodological orientation known as scientific realism, in which outcome patterns in the social world are understood as manifestations of the operation of social mechanisms in specific conducive contexts, is increasingly popular in the social sciences, including within public health and social policy. Yet, little research to date has examined evidence-informed health policymaking through a realist lens. This thesis addresses this gap. The purpose of this thesis is to explore the usefulness and explanatory value of realist approaches for the study of the use of evidence by health policymakers, and the influence of complex interventions designed to institutionalize the systematic application of evidence to health policymaking. The thesis presents two qualitative syntheses and a primary case study in pursuit of this aim. Following a survey of relevant literature (Chapter 1) and a discussion of methodological foundations (Chapter 2), a comprehensive systematic review of qualitative research on evidence-informed health policymaking is summarized (Chapter 3). The latter forms the basis for the subsequent two chapters, a thematic synthesis on the factors affecting evidence use by health policymakers (Chapter 4) and a realist synthesis on the institutionalization of evidence-informed policymaking (Chapter 5). The thesis then pivots from synthesized secondary evidence to original primary research. A qualitative realist case study on the knowledge transfer work of the West African Health Organization (WAHO) is presented (Chapter 6), culminating in the proposal of a realist program theory setting out explanations for how and under what conditions their flagship program – WAHO’s Knowledge Transfer Platform – influences the use of evidence in national health policymaking in West Africa. The thesis closes with a pair of essays that provide lessons, interpretations and critical reflections, both methodological (Chapter 7) and practical (Chapter 8)