Biochemical and Biophysical Research Communications, 2007
Capsaicin (Cap) and its analogs (CAPanalogs) have diverse effects in sensory neurons including an... more Capsaicin (Cap) and its analogs (CAPanalogs) have diverse effects in sensory neurons including analgesia, implying they modulate other cellular targets besides the TRPV1 Cap receptor. Since Cap and CAPanalogs are not largely available and their chemical synthesis is cumbersome, they have been obtained through a direct lipase-catalyzed reaction. Capsiate, the ester CAPanalog, was synthesized using a novel enzymatic transacylation one-pot strategy. Five different CAPanalogs were synthesized by amidation in 2-methyl-2-butanol with higher yields than previously reported. Voltage-dependent Ca 2+ channels (Ca v s) are among the main Ca 2+ entry paths into cells. They are classified as high-voltage-activated Ca 2+ channels (HVA) and low-voltage-activated Ca 2+ channels (LVA) constituted only by T-type channels. Though HVA Ca v s are Cap sensitive, it is not known if capsaicinoids inhibit LVA Ca v s which participate in the primary sensory neuron pain pathway. Here we first report that Cap, dihydrocapsaicin, N-VAMC 8 , N-VAMC 9 , and N-VAMC 10 can directly and partially reversibly inhibit T-type Ca v s, whereas olvanil, capsiate, and vanillylamine cannot. The Cap inhibition of T-type Ca v s was independent of TRPV1 activation.
Different green synthesis of alkyl esters of acyclovir (acyclovir prodrugs) is described. Hexanoi... more Different green synthesis of alkyl esters of acyclovir (acyclovir prodrugs) is described. Hexanoic, decanoic, dodecanoic and tetradecanoic acyclovir esters were synthesized reacting acyclovir and the respective acid anhydride in dimethyl sulfoxide (DMSO), in solvents from renewable sources and without solvent (T°03؍C). Yields in prodrugs after 10 min of reaction were Ͼ Ͼ95% using DMSO as solvent. The purification methodology was very simple, shorter and greener than previously described. The biosolvent, N,N-dimethylamide of decanoic acid, let us to obtain Ͼ Ͼ95% yield at 24 h. This oily biosolvent is not dermotoxic and the reaction crude can directly be used in topic formulations. Syntheses without solvent proceeded successfully for acyclovir esters. Indeed, dodecanoate and tetradecanoate yielding Ͼ Ͼ98% conversion of reactants in 30 min. In spite of requiring mild temperature (65°C), substrate molar ratios were lowered to 1 : 1, thus conducing to a more efficient use of raw materials. The synthetic procedures were scaled up to a 300 g batch (yield 98-99% isolated ester). These esters can be used as acyclovir prodrugs in topic formulations. The esters release from an oil/water micro-emulsion and a hydrogel formulation were tested with good results.
The design and development of greener processes that are safe and friendly is an irreversible tre... more The design and development of greener processes that are safe and friendly is an irreversible trend that is driven by sustainable and economic issues. The use of Biocatalysis as part of a manufacturing process fits well in this trend as enzymes are themselves biodegradable, require mild conditions to work and are highly specific and well suited to carry out complex reactions in a simple way. The growth of computational capabilities in the last decades has allowed Biocatalysis to develop sophisticated tools to understand better enzymatic phenomena and to have the power to control not only process conditions but also the enzyme's own nature. Nowadays, Biocatalysis is behind some important products in the pharmaceutical, cosmetic, food and bulk chemicals industry. In this review we want to present some of the most representative examples of industrial chemicals produced in vitro through enzymatic catalysis.
Biochemical and Biophysical Research Communications, 2007
Capsaicin (Cap) and its analogs (CAPanalogs) have diverse effects in sensory neurons including an... more Capsaicin (Cap) and its analogs (CAPanalogs) have diverse effects in sensory neurons including analgesia, implying they modulate other cellular targets besides the TRPV1 Cap receptor. Since Cap and CAPanalogs are not largely available and their chemical synthesis is cumbersome, they have been obtained through a direct lipase-catalyzed reaction. Capsiate, the ester CAPanalog, was synthesized using a novel enzymatic transacylation one-pot strategy. Five different CAPanalogs were synthesized by amidation in 2-methyl-2-butanol with higher yields than previously reported. Voltage-dependent Ca 2+ channels (Ca v s) are among the main Ca 2+ entry paths into cells. They are classified as high-voltage-activated Ca 2+ channels (HVA) and low-voltage-activated Ca 2+ channels (LVA) constituted only by T-type channels. Though HVA Ca v s are Cap sensitive, it is not known if capsaicinoids inhibit LVA Ca v s which participate in the primary sensory neuron pain pathway. Here we first report that Cap, dihydrocapsaicin, N-VAMC 8 , N-VAMC 9 , and N-VAMC 10 can directly and partially reversibly inhibit T-type Ca v s, whereas olvanil, capsiate, and vanillylamine cannot. The Cap inhibition of T-type Ca v s was independent of TRPV1 activation.
Different green synthesis of alkyl esters of acyclovir (acyclovir prodrugs) is described. Hexanoi... more Different green synthesis of alkyl esters of acyclovir (acyclovir prodrugs) is described. Hexanoic, decanoic, dodecanoic and tetradecanoic acyclovir esters were synthesized reacting acyclovir and the respective acid anhydride in dimethyl sulfoxide (DMSO), in solvents from renewable sources and without solvent (T°03؍C). Yields in prodrugs after 10 min of reaction were Ͼ Ͼ95% using DMSO as solvent. The purification methodology was very simple, shorter and greener than previously described. The biosolvent, N,N-dimethylamide of decanoic acid, let us to obtain Ͼ Ͼ95% yield at 24 h. This oily biosolvent is not dermotoxic and the reaction crude can directly be used in topic formulations. Syntheses without solvent proceeded successfully for acyclovir esters. Indeed, dodecanoate and tetradecanoate yielding Ͼ Ͼ98% conversion of reactants in 30 min. In spite of requiring mild temperature (65°C), substrate molar ratios were lowered to 1 : 1, thus conducing to a more efficient use of raw materials. The synthetic procedures were scaled up to a 300 g batch (yield 98-99% isolated ester). These esters can be used as acyclovir prodrugs in topic formulations. The esters release from an oil/water micro-emulsion and a hydrogel formulation were tested with good results.
The design and development of greener processes that are safe and friendly is an irreversible tre... more The design and development of greener processes that are safe and friendly is an irreversible trend that is driven by sustainable and economic issues. The use of Biocatalysis as part of a manufacturing process fits well in this trend as enzymes are themselves biodegradable, require mild conditions to work and are highly specific and well suited to carry out complex reactions in a simple way. The growth of computational capabilities in the last decades has allowed Biocatalysis to develop sophisticated tools to understand better enzymatic phenomena and to have the power to control not only process conditions but also the enzyme's own nature. Nowadays, Biocatalysis is behind some important products in the pharmaceutical, cosmetic, food and bulk chemicals industry. In this review we want to present some of the most representative examples of industrial chemicals produced in vitro through enzymatic catalysis.
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Papers by Ruben de Regil