P h D   T H E S I S

Promoting scientific literacy in our society is an ambitious goal that could be achieved through the interaction of the different actors involved. For doing so, it is essential to incorporate methodological innovations aimed at developing scientific skills and increasing scientific vocations, such as incorporating the didactic approach of inquiry, a didactic transposition of scientific research. Despite the consensus on the value of inquiry-based science education (IBSE), its application in the science classroom remains limited due to the difficulties teachers encounter in its practice and a whole series of teaching perceptions in this regard, like supposing that this approach complicates the classroom management, that it is incompatible with the extension of the curricula or that it is only appropriate with high ability students. Therefore, it is necessary to consider all these aspects in the pre-service science teachers' training. Hence, the main objective of this Doctoral Thesis is to promote the inquiry approach in pre-service science teachers (PSSTs) of Secondary Education.

For this, we address the design, development and analysis of a training program (TP) on the IBSE teaching specific to Physics and Chemistry PSSTs. The program has been designed based on the most relevant conclusions found in the literature on the matter, integrating instruction in the knowledge of the pedagogical content on inquiry, providing support in the design and implementation of this type of activity and favouring its transfer to practice. The activities that make up the training proposal are described, as well as the research instruments used and the analysis methodology (mixed-methods). The relevance and evolution of the perceptions and emotions about IBSE of the future Physics and Chemistry teachers are examined, analyzing, among other aspects, the relationships between their beliefs and the inquiry processes, as well as the ability to develop a teaching-learning proposal with an inquiry approach.

The results show, in general terms, an initial perception of the PSSTs favourable to the inquiry as a teaching approach, reinforced by a positive emotional profile, and with the TP designed contributing to the development of the necessary skills for the design and implementation of inquiry activities in the Secondary Education classrooms. Finally, some general considerations are raised about the training proposal and the results obtained, as well as the possible continuity and pedagogical implications of the research carried out. 

The present work is on the total synthesis of the natural compounds and/or analogues of Bengamides, Gummiferol and Depudecin. The target molecules, selected in virtue of their prominent biological activity as antibiotic and antitumor agents are featured by the presence of one or two epoxide groups and were synthesized by application of a novel methodology of asymmetric epoxidation based on the use of a new class of chiral sulfur ylides. 

The aim of every total synthesis discussed in this thesis is to develop an efficient route to the final product in relation to the introduction of stereogenic elements. The biological background as well as the synthetic history of each target compounds will be introduced prior to discussion of the actual synthesis. 

Chapter 2 provides a comprehensive review of the current research status of bengamides and includes a brief introduction to the structure, classification and precedents together with their eminent role as antitumor agents. As main objective, the major part of this chapter summarizes the strategies and experimental approaches to a new class of bengamide analogues containing either one or two epoxides throughout the polyketide chain, that might mimic the mode of action of fumagillin. With the purpose of better understanding the mechanism of action exhibited by bengamides, azido derivative in position C4 will be also described. Finally, the biological evaluation of some of the analogues synthesized will be discussed.

Chapter 3 describes the synthesis of gummiferol, a cytotoxic metabolite with antitumor activity that possesses two consecutive oxirane rings conjugated to a triacetylene moiety, by means of the use of chiral sulfur ylides. The isolation and characterization is described across this chapter as well as the synthesis of the natural product and analogues reported to date. In this way, the second objective will be to develop an alternative to the previous synthesis of gummiferol by generating the epoxides in a stereoselective fashion by means of the chiral sulfur ylide methodology. 

In Chapter 4, depudecin, a new microbial metabolite with promising antiangiogenic activity is presented together with its biological synthesis. Hence, our ultimate goal will be to stablish an efficient and straightforward route toward its total synthesis. 

A further chapter (Chapter 5) has been included, displaying additional synthetic projects carried out during this thesis. Hence, contributions to the synthesis of the natural products globomycin, epibestatin and celebeside A, as well as the protease inhibitor AcArgValArgArgCMK, are described by using the solid phase synthesis methodology.

Finally, a summary of the outcome of this work, a general discussion and perspectives are provided in Chapter 6.