O objetivo do experimento I foi determinar o efeito da inclusão de narasina na mistura mineral para novilhas alimentadas com forragem. Foram utilizadas 30 novilhas Nelore, distribuídas em 10 baias (3 animais/baia) com peso médio inicial de 222 ± 3,0 kg. As novilhas foram alimentadas diariamente com pré-secado de cynodon spp. Os tratamentos experimentais foram 0, 650 e 1300 mg de narasina/kg de mistura mineral (0N, 6,5N e 13N, respectivamente). As variáveis analisadas foram consumo de matéria seca (CMS), consumo de mistura mineral (CMM) diário, ganho médio diário (GMD), conversão alimentar (CA) e variação na ingestão da IMM. O delineamento experimental utilizado foi change-over (todas as baias passaram por todos os tratamentos), com um período experimental de 28 dias, e 7 dias destinado ao período tampão (wash-out). A adição de narasina não afetou o CMM (P = 0,75) e nem o CMS (P = 0,69). No entanto, o tratamento 13N aumentou o GMD (P = 0,02) e, consequentemente, melhorou a CA (P = 0,05) em comparação com os animais do grupo 0N e 6,5N. Os resultados indicam que houve uma variação da IMM de cada baia e ao longo do período experimental, e essa variação foi semelhante para todos tratamentos. O objetivo do experimento II foi avaliar o efeito da inclusão de narasina no suplemento mineral para o desempenho de novilhas alimentadas com dietas contendo alto teor de concentrado. Foram utilizadas 60 novilhas Nelore, distribuídas em 20 baias (3 animais/baia) com peso médio inicial 245 ± 4,3 kg. As novilhas foram alimentadas diariamente com uma dieta contendo aproximadamente 16% de bagaço de cana e 84% de concentrado. Os tratamentos experimentais foram 0N e 13N. As variáveis analisadas foram as mesmas do experimento I. O delineamento experimental utilizado foi cross-over (todas as baias passaram por todos os tratamentos), com um período experimental de 28 dias, e 7 dias destinado ao período tampão (wash-out). A inclusão de 1300 mg de narasina/kg de mistura mineral não afetou o GMD (P = 0,06), CMS (P = 0,56) ou CMM (P = 0,33). No entanto, a adição de narasina diminuiu a CA (P = 0,05) em relação ao grupo controle. Semelhante ao experimento I, houve uma grande variação no CMM entre baias e ao longo do período experimental. O objetivo do experimento III foi avaliar se a inclusão de cloreto de sódio (NaCl) como inibidor e o milho moído como estimulador de consumo de mistura mineral, poderia regularizar a frequência e o consumo individual desse suplemento. Foram utilizadas 30 novilhas Nelore (22 meses), distribuídas em 10 baias (3 animais/baia) com peso médio inicial 294 ± 3,7 kg. As novilhas foram alimentadas diariamente com pré-secado de Cynodon spp. ad libitum. Os tratamentos experimentais foram controle (mistura mineral), 10MM (90% mistura mineral e 10% milho moído), 10M25NaCl (65% mistura mineral, 10% milho moído e 25% NaCl) e 10M50NaCl (40% mistura mineral, 10% milho moído e 50% NaCl). O delineamento experimental utilizado foi igual ao Experimento I. O período experimental teve duração de 15 dias, 7 dias destinados ao período tampão (washout). A análise de variação do CMM utilizado, foi o erro padrão da média (*EPM) de cada dia para cada tratamento (VCMM). O CMS (P = 0,81), GMD (P = 0,27) e CA (P = 0,31) não diferiram entre os tratamentos. A adição de milho moído aumentou e a inclusão de NaCl reduziu o CMM (P < 0,01). O mesmo aconteceu com a VCMM (P < 0,01), onde o EPM aumentou com a inclusão de milho e reduziu quando adicionado de NaCl / The objective of the first trial was to determine the effect of narasin inclusion into the mineral mix for heifers fed high forage diets. Thirty Nellore heifers with initial body weight of 222 ± 3.0 kg were used and they were distributed in ten pens (three animals per pen) and fed daily with Cynodon spp. haylage. The experimental treatments were 0N, 6.5N and 13N, with the inclusion of 0, 650 and 1300 mg of narasina/kg of MM, respectively. The variables analyzed were dry matter intake (DMI), mineral mix intake (MMI), average daily gain (ADG), feed:gain ratio (F:G) and MMI variation (MMIV). The experimental design used was change over, where all pens go through all treatments, with a 28 days' experimental period and seven days of wash out. The addition of narasin did not affect neither the MMI (P = 0.75) nor the DMI (P = 0.69). However, when compared to 0N and 6.5N, the addition of 1300 mg of narasin increased ADG (P = 0.02), consequently improving the F:G (P = 0.05). The results indicate that there was a MMIV in each pen and over the experimental period, and that variation was similar for all treatments. The objective of the second trial was to evaluate the effects of narasin inclusion into the MM over the performance of heifers fed high concentrate diets. Sixty Nellore heifers with initial BW of 245 ± 4,3 kg were used. They were distributed in 20 pens (3 animals/pen) and fed daily with a diet containing approximately 16% sugar cane bagasse and 84% concentrate. The experimental treatments were 0N and 13N, with the inclusion of 0 and 1300 mg of narasin/kg of MM, respectively. The experimental design was cross over, in which all pens go through all treatments, with a 28 days experimental period and seven days of wash out. The inclusion of 1300 mg of narasin/kg of MM did not affect the ADG (P = 0.06), the DMI (P = 0.56) and the MMI (P = 0.33). However, it did improve the F:G (P = 0.05) when compared to the control. Similar to the first trial, there was a big variation in MMI between the pens and along the experimental period. The objective of the third trial was to evaluate if the inclusion of Sodium Chloride (NaCl) as an inhibitor and ground corn (Gc) as a MM intake stimulator could regularize the individual frequency and amount of the supplement intake. Thirty Nellore heifers with 22 months old and an initial BW of 294 ± 3,7 kg were used. They were distributed in ten pens (3 animals/pen) and fed daily, ad libitum, with Cynodon spp. haylage. The experimental treatments were control (100% MM), 10%Gc (90% MM and 10% Gc), 10%Gc+25%NaCl (65% MM, 10% Gc and 25% NaCl) and 10%Gc+50%NaCl (40% MM, 10% Gc and 50% NaCl). The experimental design used was the same as the first trial, with a 15 days' experimental period and 7 days of wash out. The variance analysis used was the mean standard error of each day for each treatment. The DMI (P = 0.92), ADG (P = 0.51) and F:G (P = 0.98) did not differ between treatments. But the addition of Gc increased the MMI and the inclusion of NaCl decreased it (P < 0.01). The same happened with the MMIV (P < 0.01), where the mean standard error increased with the inclusion of Gc and decreased when NaCl was added

O objetivo do experimento I foi determinar o efeito da inclusão de narasina na mistura mineral para novilhas alimentadas com forragem. Foram utilizadas 30 novilhas Nelore, distribuídas em 10 baias (3 animais/baia) com peso médio inicial de 222 ± 3,0 kg. As novilhas foram alimentadas diariamente com pré-secado de cynodon spp. Os tratamentos experimentais foram 0, 650 e 1300 mg de narasina/kg de mistura mineral (0N, 6,5N e 13N, respectivamente). As variáveis analisadas foram consumo de matéria seca (CMS), consumo de mistura mineral (CMM) diário, ganho médio diário (GMD), conversão alimentar (CA) e variação na ingestão da IMM. O delineamento experimental utilizado foi change-over (todas as baias passaram por todos os tratamentos), com um período experimental de 28 dias, e 7 dias destinado ao período tampão (wash-out). A adição de narasina não afetou o CMM (P = 0,75) e nem o CMS (P = 0,69). No entanto, o tratamento 13N aumentou o GMD (P = 0,02) e, consequentemente, melhorou a CA (P = 0,05) em comparação com os animais do grupo 0N e 6,5N. Os resultados indicam que houve uma variação da IMM de cada baia e ao longo do período experimental, e essa variação foi semelhante para todos tratamentos. O objetivo do experimento II foi avaliar o efeito da inclusão de narasina no suplemento mineral para o desempenho de novilhas alimentadas com dietas contendo alto teor de concentrado. Foram utilizadas 60 novilhas Nelore, distribuídas em 20 baias (3 animais/baia) com peso médio inicial 245 ± 4,3 kg. As novilhas foram alimentadas diariamente com uma dieta contendo aproximadamente 16% de bagaço de cana e 84% de concentrado. Os tratamentos experimentais foram 0N e 13N. As variáveis analisadas foram as mesmas do experimento I. O delineamento experimental utilizado foi cross-over (todas as baias passaram por todos os tratamentos), com um período experimental de 28 dias, e 7 dias destinado ao período tampão (wash-out). A inclusão de 1300 mg de narasina/kg de mistura mineral não afetou o GMD (P = 0,06), CMS (P = 0,56) ou CMM (P = 0,33). No entanto, a adição de narasina diminuiu a CA (P = 0,05) em relação ao grupo controle. Semelhante ao experimento I, houve uma grande variação no CMM entre baias e ao longo do período experimental. O objetivo do experimento III foi avaliar se a inclusão de cloreto de sódio (NaCl) como inibidor e o milho moído como estimulador de consumo de mistura mineral, poderia regularizar a frequência e o consumo individual desse suplemento. Foram utilizadas 30 novilhas Nelore (22 meses), distribuídas em 10 baias (3 animais/baia) com peso médio inicial 294 ± 3,7 kg. As novilhas foram alimentadas diariamente com pré-secado de Cynodon spp. ad libitum. Os tratamentos experimentais foram controle (mistura mineral), 10MM (90% mistura mineral e 10% milho moído), 10M25NaCl (65% mistura mineral, 10% milho moído e 25% NaCl) e 10M50NaCl (40% mistura mineral, 10% milho moído e 50% NaCl). O delineamento experimental utilizado foi igual ao Experimento I. O período experimental teve duração de 15 dias, 7 dias destinados ao período tampão (washout). A análise de variação do CMM utilizado, foi o erro padrão da média (*EPM) de cada dia para cada tratamento (VCMM). O CMS (P = 0,81), GMD (P = 0,27) e CA (P = 0,31) não diferiram entre os tratamentos. A adição de milho moído aumentou e a inclusão de NaCl reduziu o CMM (P < 0,01). O mesmo aconteceu com a VCMM (P < 0,01), onde o EPM aumentou com a inclusão de milho e reduziu quando adicionado de NaCl / The objective of the first trial was to determine the effect of narasin inclusion into the mineral mix for heifers fed high forage diets. Thirty Nellore heifers with initial body weight of 222 ± 3.0 kg were used and they were distributed in ten pens (three animals per pen) and fed daily with Cynodon spp. haylage. The experimental treatments were 0N, 6.5N and 13N, with the inclusion of 0, 650 and 1300 mg of narasina/kg of MM, respectively. The variables analyzed were dry matter intake (DMI), mineral mix intake (MMI), average daily gain (ADG), feed:gain ratio (F:G) and MMI variation (MMIV). The experimental design used was change over, where all pens go through all treatments, with a 28 days' experimental period and seven days of wash out. The addition of narasin did not affect neither the MMI (P = 0.75) nor the DMI (P = 0.69). However, when compared to 0N and 6.5N, the addition of 1300 mg of narasin increased ADG (P = 0.02), consequently improving the F:G (P = 0.05). The results indicate that there was a MMIV in each pen and over the experimental period, and that variation was similar for all treatments. The objective of the second trial was to evaluate the effects of narasin inclusion into the MM over the performance of heifers fed high concentrate diets. Sixty Nellore heifers with initial BW of 245 ± 4,3 kg were used. They were distributed in 20 pens (3 animals/pen) and fed daily with a diet containing approximately 16% sugar cane bagasse and 84% concentrate. The experimental treatments were 0N and 13N, with the inclusion of 0 and 1300 mg of narasin/kg of MM, respectively. The experimental design was cross over, in which all pens go through all treatments, with a 28 days experimental period and seven days of wash out. The inclusion of 1300 mg of narasin/kg of MM did not affect the ADG (P = 0.06), the DMI (P = 0.56) and the MMI (P = 0.33). However, it did improve the F:G (P = 0.05) when compared to the control. Similar to the first trial, there was a big variation in MMI between the pens and along the experimental period. The objective of the third trial was to evaluate if the inclusion of Sodium Chloride (NaCl) as an inhibitor and ground corn (Gc) as a MM intake stimulator could regularize the individual frequency and amount of the supplement intake. Thirty Nellore heifers with 22 months old and an initial BW of 294 ± 3,7 kg were used. They were distributed in ten pens (3 animals/pen) and fed daily, ad libitum, with Cynodon spp. haylage. The experimental treatments were control (100% MM), 10%Gc (90% MM and 10% Gc), 10%Gc+25%NaCl (65% MM, 10% Gc and 25% NaCl) and 10%Gc+50%NaCl (40% MM, 10% Gc and 50% NaCl). The experimental design used was the same as the first trial, with a 15 days' experimental period and 7 days of wash out. The variance analysis used was the mean standard error of each day for each treatment. The DMI (P = 0.92), ADG (P = 0.51) and F:G (P = 0.98) did not differ between treatments. But the addition of Gc increased the MMI and the inclusion of NaCl decreased it (P < 0.01). The same happened with the MMIV (P < 0.01), where the mean standard error increased with the inclusion of Gc and decreased when NaCl was added

Zum Studium des prophylaktischen Einflusses ausgewählter antibiotischer Leistungsförderer [Avilamycin (10 ppm), Avoparcin (15 ppm), Virginiamycin (20 ppm)] und ionophorer Antikokzidia [Monensin (100 ppm), Narasin (70 ppm)] sowie des metaphylaktischen bzw. therapeutischen Einsatzes von Tylosin [Tylan 0,5 g/l H2O] auf das Auftreten und die Ausprägung der Clostridium (Cl.) perfringens-Enterotoxämie (CPE) wurden Untersuchungen an insgesamt 33 Versuchsgruppen mit 825 Broilerküken durchgeführt. Die Erkrankung konnte mittels intraduodenaler Inokulation einer Vollkultur Cl. perfringens Typ A (ATCC 3624) sicher reproduziert werden. Die Morbiditätsrate betrug in allen infizierten Gruppen 100 %. An klinischer Symptomatik zeigte sich hauptsächlich profuser wässriger Durchfall. Schwerere Störungen, Apathie und Anorexie, waren selten und in allen beobachteten Fällen vom schnellen Tod des betreffenden Tieres begleitet. Allgemein fiel auf, daß die infizierten und nicht medikamentierten Tiere schneller und länger erkrankten. Bei infizierten und unmedikamentierten Tieren ergab sich eine Mortalitätsrate von 16 bis 36 %, in den medikamentierten Gruppen maximal 8 %. Tylosin zeigte eine sehr gute metaphylaktischen bzw. therapeutische Wirkung. Die Lebendmasseentwicklung betrachtend, konnte Avoparcin unter den Leistungsförderern beste Ergebnisse erzielen. Ähnliche Resultate wurden in den Kombinationsgruppen [Avilamycin plus Monensin oder Narasin] bzw. mittels Narasin erreicht. In absteigender Reihenfolge zeigten Avilamycin, Virginiamycin und Monensin eine geringere leistungsfördernde Wirkung. Die Bestimmung fäkaler bzw. ileozäkaler Clostridienkonzentrationen lebender, respektive verendeter Hühner erbrachte nur wenige und relativ unbedeutende statistisch gesicherte Korrelationen zu anderen Ergebnissen. Es konnten keine Zusammenhänge zwischen Erregerzahl und Lebendmassezunahme, bzw. Todesursache, aufgedeckt werden. Die Resultate aus allen Versuchen zusammenfassend, müssen den Kombinationen von Avilamycin mit Narasin bzw. Monensin beste Effekte hinsichtlich einer positiven Beeinflussung CPE-bedingter Morbidität, Mortalität und Lebendmasseverluste bescheinigt werden. Tylosin war in der Lage, die Verlustzahlen durch CPE rasch zu senken. Für die Ausprägung kompensatorischer Effekte hinsichtlich der Lebendmasseverluste unter der Infektion muß mit einer größeren Zeitspanne gerechnet werden. Die Polyether und auch Avilamycin sind als Futtermittelzusatzstoffe für die europäische Geflügelhaltung zugelassen. Durch die ständige Kokzidiosebedrohung in den Hühnerbeständen kann auf einen prophylaktischen Einsatz antikokzidieller Futtermittelzusatzstoffe momentan nicht verzichtet werden. Es ist zu vermuten, daß es durch den simultanen Einsatz von Polyether und Leistungsförderer zu einer positiven Beeinflussung der schädigenden Wechselwirkungen von Kokzidien und Cl. perfringens im Darm kommt. Bei vorhandener Empfindlichkeit der Eimerien sollte dies sowohl die Bekämpfung von CPE als auch von Kokzidiosen begünstigen. Der positive Eindruck von Avoparcin spielt, bedingt durch das europaweite Verbot, momentan für die Praxis keine Rolle. Die Entwicklungstendenzen auf dem Sektor antibiotisch wirksamer Futtermittelzusatzstoffe, eng verknüpft mit der bakteriellen Resistenzproblematik, werden in der Arbeit ausführlich diskutiert. / Investigations with 825 chickens in 33 trials were performed in order to find out the prophylactic effect of selected antibiotic growth promoters [avilamycin (10 ppm), avoparcin (15 ppm) virginiamycin (20 ppm)] and polyether ionophore antibiotics [monensin (100 ppm), narasin (70 ppm)] on the incidence of Clostridium (Cl.) perfringens enterotoxemia (CPE) in chickens as well as the therapeutic resp. metaphylactic influence of tylosin [Tylan 0,5 g/l H20]. The enterotoxemia could be reproduced regularly by intraduodenal infection with high numbers of vegetative cells of Cl. perfringens type A (ATCC 3624). The morbidity rate always reached 100 %. In spite of a profuse and watery diarrhoea the chickens normally showed no further considerable disturbances of the general status. Apathy or anorexia were rather rare and immediately followed by Exitus letalis of the related chickens. It was striking that the infected and non-medicated broilers contracted the disease more quickly and for a longer time. The mortality rate among the infected and non-medicated animals was 16 to 36 %, among the medicated groups max. 8 %. Tylosin showed a considerable metaphylactic effect in decreasing CPE mortality. The avoparcin group showed the best weight gain among the growth promoters, comparable to the results by means of the combinations [avilamycin + monensin or narasin] or narasin only. Decreasingly avilamycin, virginiamycin and monensin were less successful. Analysing the faecal resp. ileocecal quantities of Cl. perfringens adduced only a few statistically guaranteed correlation with other results. There was no causal connection between numbers of Cl. perfringens and life weight development. It was impossible to discover a numerical threshold of germs responsible for the death of the chickens. Summarising all the results of the entire attempts the combinations of avilamycin and narasin resp. monensin were the most effective concerning the reduction of morbidity, mortality and life weight losses by CPE. By application of tylosin it was possible to stop the mortality rate quickly. But it needs more time to achieve reductions of the CPE related weight losses. The two polyethers and also avilamycin are still admitted in the European Union. Currently an abandonment of anticoccidial feed supplements seems to be impossible due to the present danger of coccidiosis in poultry. By means of monensin/narasin plus avilamycin the adverse health effects of interactions of both pathogens should be reduced. Presupposing susceptibility of the coccida this should be a notable contribution to a better controlling and to the prevention of CPE and coccidiosis, too.

Zum Studium des prophylaktischen Einflusses ausgewählter antibiotischer Leistungsförderer [Avilamycin (10 ppm), Avoparcin (15 ppm), Virginiamycin (20 ppm)] und ionophorer Antikokzidia [Monensin (100 ppm), Narasin (70 ppm)] sowie des metaphylaktischen bzw. therapeutischen Einsatzes von Tylosin [Tylan 0,5 g/l H2O] auf das Auftreten und die Ausprägung der Clostridium (Cl.) perfringens-Enterotoxämie (CPE) wurden Untersuchungen an insgesamt 33 Versuchsgruppen mit 825 Broilerküken durchgeführt. Die Erkrankung konnte mittels intraduodenaler Inokulation einer Vollkultur Cl. perfringens Typ A (ATCC 3624) sicher reproduziert werden. Die Morbiditätsrate betrug in allen infizierten Gruppen 100 %. An klinischer Symptomatik zeigte sich hauptsächlich profuser wässriger Durchfall. Schwerere Störungen, Apathie und Anorexie, waren selten und in allen beobachteten Fällen vom schnellen Tod des betreffenden Tieres begleitet. Allgemein fiel auf, daß die infizierten und nicht medikamentierten Tiere schneller und länger erkrankten. Bei infizierten und unmedikamentierten Tieren ergab sich eine Mortalitätsrate von 16 bis 36 %, in den medikamentierten Gruppen maximal 8 %. Tylosin zeigte eine sehr gute metaphylaktischen bzw. therapeutische Wirkung. Die Lebendmasseentwicklung betrachtend, konnte Avoparcin unter den Leistungsförderern beste Ergebnisse erzielen. Ähnliche Resultate wurden in den Kombinationsgruppen [Avilamycin plus Monensin oder Narasin] bzw. mittels Narasin erreicht. In absteigender Reihenfolge zeigten Avilamycin, Virginiamycin und Monensin eine geringere leistungsfördernde Wirkung. Die Bestimmung fäkaler bzw. ileozäkaler Clostridienkonzentrationen lebender, respektive verendeter Hühner erbrachte nur wenige und relativ unbedeutende statistisch gesicherte Korrelationen zu anderen Ergebnissen. Es konnten keine Zusammenhänge zwischen Erregerzahl und Lebendmassezunahme, bzw. Todesursache, aufgedeckt werden. Die Resultate aus allen Versuchen zusammenfassend, müssen den Kombinationen von Avilamycin mit Narasin bzw. Monensin beste Effekte hinsichtlich einer positiven Beeinflussung CPE-bedingter Morbidität, Mortalität und Lebendmasseverluste bescheinigt werden. Tylosin war in der Lage, die Verlustzahlen durch CPE rasch zu senken. Für die Ausprägung kompensatorischer Effekte hinsichtlich der Lebendmasseverluste unter der Infektion muß mit einer größeren Zeitspanne gerechnet werden. Die Polyether und auch Avilamycin sind als Futtermittelzusatzstoffe für die europäische Geflügelhaltung zugelassen. Durch die ständige Kokzidiosebedrohung in den Hühnerbeständen kann auf einen prophylaktischen Einsatz antikokzidieller Futtermittelzusatzstoffe momentan nicht verzichtet werden. Es ist zu vermuten, daß es durch den simultanen Einsatz von Polyether und Leistungsförderer zu einer positiven Beeinflussung der schädigenden Wechselwirkungen von Kokzidien und Cl. perfringens im Darm kommt. Bei vorhandener Empfindlichkeit der Eimerien sollte dies sowohl die Bekämpfung von CPE als auch von Kokzidiosen begünstigen. Der positive Eindruck von Avoparcin spielt, bedingt durch das europaweite Verbot, momentan für die Praxis keine Rolle. Die Entwicklungstendenzen auf dem Sektor antibiotisch wirksamer Futtermittelzusatzstoffe, eng verknüpft mit der bakteriellen Resistenzproblematik, werden in der Arbeit ausführlich diskutiert. / Investigations with 825 chickens in 33 trials were performed in order to find out the prophylactic effect of selected antibiotic growth promoters [avilamycin (10 ppm), avoparcin (15 ppm) virginiamycin (20 ppm)] and polyether ionophore antibiotics [monensin (100 ppm), narasin (70 ppm)] on the incidence of Clostridium (Cl.) perfringens enterotoxemia (CPE) in chickens as well as the therapeutic resp. metaphylactic influence of tylosin [Tylan 0,5 g/l H20]. The enterotoxemia could be reproduced regularly by intraduodenal infection with high numbers of vegetative cells of Cl. perfringens type A (ATCC 3624). The morbidity rate always reached 100 %. In spite of a profuse and watery diarrhoea the chickens normally showed no further considerable disturbances of the general status. Apathy or anorexia were rather rare and immediately followed by Exitus letalis of the related chickens. It was striking that the infected and non-medicated broilers contracted the disease more quickly and for a longer time. The mortality rate among the infected and non-medicated animals was 16 to 36 %, among the medicated groups max. 8 %. Tylosin showed a considerable metaphylactic effect in decreasing CPE mortality. The avoparcin group showed the best weight gain among the growth promoters, comparable to the results by means of the combinations [avilamycin + monensin or narasin] or narasin only. Decreasingly avilamycin, virginiamycin and monensin were less successful. Analysing the faecal resp. ileocecal quantities of Cl. perfringens adduced only a few statistically guaranteed correlation with other results. There was no causal connection between numbers of Cl. perfringens and life weight development. It was impossible to discover a numerical threshold of germs responsible for the death of the chickens. Summarising all the results of the entire attempts the combinations of avilamycin and narasin resp. monensin were the most effective concerning the reduction of morbidity, mortality and life weight losses by CPE. By application of tylosin it was possible to stop the mortality rate quickly. But it needs more time to achieve reductions of the CPE related weight losses. The two polyethers and also avilamycin are still admitted in the European Union. Currently an abandonment of anticoccidial feed supplements seems to be impossible due to the present danger of coccidiosis in poultry. By means of monensin/narasin plus avilamycin the adverse health effects of interactions of both pathogens should be reduced. Presupposing susceptibility of the coccida this should be a notable contribution to a better controlling and to the prevention of CPE and coccidiosis, too.

Cet ouvrage traite principalement de la synthèse de motifs polypropionates de type stéréopentade ainsi qu’une application à la synthèse d’une molécule naturelle possèdant des propriétés biologiques. La stratégie envisagée pour l’élaboration de ces motifs récurrents dans plusieurs structures d’origine naturelle fait appel à la chimie des radicaux. Cette thèse se divise en différents chapitres dans lesquels la versatilité de la méthodologie développée sera démontrée. En premier lieu, il sera question de présenter l’importance de la synthèse de motifs polypropionates. Le domaine couvert par la chimie de ces molécules complexes hautement fonctionnalisées a contribué énormément à l’avancement de nos connaissances en synthèse organique, particulièrement dans le contexte des réactions impliquant des molécules acyliques. Une brève description des méthodes connues est présentée afin de saisir l’étendue des défis restants pour construire efficacement tous les isomères possibles des polypropionates de type stéréopentade. La stratégie proposée est basée sur une approche contrôlée entièrement par le substrat. Ce contrôle s’appuie sur le choix judicieux de l’acide de Lewis activant les deux réactions impliquées, soit la réaction de Mukaiyama et le transfert d’hydrogène. La seconde section de cette thèse concerne principalement le développement d’une réaction de Mukaiyama impliquant un éther d’énol silylé portant un lien pouvant être homolytiquement brisé dans la réaction suivante et un aldéhyde de type propionate. Le contrôle de l’aldolisation provient de la nature de l’acide de Lewis. Une espèce monodentate (BF3·OEt2) génère une relation 3,4-syn selon le modèle dit Felkin-Anh tandis que les acides de Lewis bidentates mènent à la relation 3,4-anti via un état de transition définit comme Cram-chélate. Une optimisation des conditions réactionnelles en variant l’acidité et la stoechiométrie de l’acide de Lewis de titane a permis de construire diastéréosélectivement le produit de Mukaiyama ayant une relation 3,4-anti. En outre, la nature des complexes impliqués dans ces réactions a été élucidée par des études RMN 13C à basse température. Une fois les précurseurs radicalaires synthétisés, notre méthodologie de réduction par transfert d’hydrogène contrôlée également par les acides de Lewis s’avère très efficace. Les acides de Lewis dérivés d’aluminium mènent sélectivement à la relation 2,3-syn selon un contrôle endocyclique tandis que les acides de Lewis de bore permettent la création des relations 2,3-anti en se basant sur une stabilisation par les divers facteurs de contrôle de molécules acycliques. Cette stratégie novatrice nous a ainsi permis de construire efficacement les 16 diastéréoisomères possibles. Le chapitre suivant concerne l’application de cette méthodologie à la synthèse de l’hémisphère ouest de la salinomycine et de la narasine. Plusieurs défis synthétiques ont été relevés à cette occasion par la présence de nombreux centres stéréogènes contigus. Nous avons réalisé que la relation stéréochimique 2,3-anti de la salinomycine n’est pas accessible sélectivement par la chimie des radicaux via l’effet exocyclique. Des études ont été entreprises afin de comprendre cette perte de sélectivité. Les conclusions suggèrent que les substituants sur le cycle imposent un biais conformationnel conduisant à des faibles sélectivités. Une alternative utilisant un réactif de crotylsilane chiral a été développée pour arriver à la molécule cible. Cette situation est différente dans le cas de la narasine où la présence du méthyle sur le carbone en position β du radical bloque efficacement l’approche d’une des faces d’attaque par l’hydrure. Des sélectivités impressionnantes nous ont permis de construire le fragment C1-C9 de la narasine de manière expéditive et efficace. Finalement, l’élongation sélective utilisant à nouveau la séquence d’aldolisation de Mukaiyama/réduction radicalaire suivie d’un couplage de type aldol stéréosélectif conduit au fragment C1-C17 de la narasine (hémisphère ouest)en 19 étapes avec un rendement global de l’ordre de 7 %. En dernier lieu, nous nous sommes penchés sur la réactivité des α-bromo-β- alkoxycétones lors de transfert d’hydrogène. Nous avons découvert que la chimie de ces derniers pourrait s’avérer utile dans le contexte de la synthèse de motifs complexes polypropionates. La présence d’un centre stéréogène de l’autre coté de la cétone semble avoir un impact sur la sélectivité. / This thesis focuses on a new methodology for the synthesis of polypropionate stereopentads with an application to the synthesis of a natural molecule that possess interesting biological properties. The key steps of our strategy to elaborate those motifs will use radical chemistry previously developped in our group. First, the importance of synthesizing polypropionate motifs is presented. In recent years, polypropionate systems have stimulated extensive interest due to their association with a broad spectrum of biologically active targets with proven or potential use in medicine, including those with antibiotic and anticancer properties. Many of the approaches reported used chiral reagents and took advantage of double asymmetric induction. Not surprisingly, mismatched scenarios were at times noticed and yet, no single strategy has been reported leading directly to all 16 stereopentad diastereoisomers. Thus, the rapid and facile assembly of the polypropionate framework would be very beneficial and is still an active area of research. The second section of this work describes our contribution to this area with the development of a fully substrate-controlled sequence of Mukaiyama aldol reaction followed by a hydrogen transfer reaction on aldehydes having the stereotriad array. The aldol reaction can be performed under Felkin-Anh or Cram-chelate pathway to give either the 3,4-syn or 3,4-anti relationship, respectively. This reaction was optimized using different Lewis acids to give excellent yield and diastereoselectivity. We found that an excess of TiCl3(OiPr) in our Mukaiyama reactions increased the chelating ability of the Lewis acid, thus leading to improved diastereoselectivity. Low temperature 13C NMR was performed to obtain more information on the complexes present in solution. Once the radical precursors were obtained, the hydrogen transfer step was performed. Aluminum-containing Lewis acids led to the exclusive formation of the 2,3- syn isomer under the endocyclic effect while controlling factors described for acyclic molecules were sufficient enough to give the 2,3-anti as a sole diastereoisomer, such as cases in which a boron-containing Lewis acid was added prior to the tin hydride. One limitation was observed with this scenario and resolved using the exocyclic effect to access all 16 polypropionate stereopentad motifs. To further demonstrate the synthethic potential of our methodology, we engaged on the synthesis of the western hemisphere of both salinomycin and narasin. The synthetic challenges related with these molecules are numerous due to the large number of adjacent stereogenic centers. We realized that the 2,3-anti stereochemical relation of salinomycin was not selectively accessible via radical chemistry under the exocyclic effect. Different substrates were tested to understand this limitation and we concluded that the substituents on the ring impose a conformationnal bias unfavorable to good selectivty. Still, we found an alternative employing a chiral crotylsilane to access this 2,3-anti relationship α to the six-membered ring. This situation is different in the case of narasin where the β-methyl substituent blocks efficiently the hydride attack from the upper face. Impressive selectivities were observed and the synthesis of the C1-C9 fragment of narasin was accomplished in an expeditive manner. Finally, the elongation using a second sequence of stereoselective Mukaiyama aldol reaction/radical reduction followed by an aldol coupling led to the construction of the western hemisphere of narasin in 19 synthethic steps with an overall yield of 7 %. Finally, we decided to focus our attention to the chemistry of α-bromo-β- alkoxyketones in hydrogen transfer reactions. We found that their ability to give selective transformations could be beneficial in the context of synthesizing complex polypropionate motifs. The presence of a stereogenic center on the other side of the ketone seemed to have a great impact on the selectivity.