The Pseudomonas fluorescens (P. cepacia) lipase-catalyzed irreversible transesterification of 2-p... more The Pseudomonas fluorescens (P. cepacia) lipase-catalyzed irreversible transesterification of 2-phenyl-1.2~propanediol la is not enantioselective, whereas the dials lb and lc am enzymatically resolved with the same procedure to (S)-lb and lc (>98 and 92% e.e.) and the (R)-acetates 2b and 2c (92% e.e.).
Reaction of Glycidyl p-Nitrobenzoate with Et2A1CN.'O To a solution of glycidyl p-nitrobenzoate (3... more Reaction of Glycidyl p-Nitrobenzoate with Et2A1CN.'O To a solution of glycidyl p-nitrobenzoate (34 mg, 0.15 mmol, racemic mixture) in toluene (5 mL) was added Et2A1CN (1.5 M solution in toluene, Alfa, 0.1 mL, 0.15 mmol) at room temperature. After 5 min, the homogeneous yellow solution was diluted with ether (30 mL) and then washed with 10% H2SO4, saturated NaHC03,
This work describes a sensitive high-performance liquid chromatography (HPLC) method for the quan... more This work describes a sensitive high-performance liquid chromatography (HPLC) method for the quantification of aloesin and aloeresin A in alcoholic beverages containing aloe as a flavoring agent. The compounds were prepared from Aloe ferox juice. Sephadex LH20 and ion-exchange resin AG1X2 column chromatography were used for aloesin. Aloeresin A was obtained by Sephadex LH20 and silica gel column chromatography followed by purification on Discovery DSC-18 solid-phase extraction tubes. A 98 mg amount of aloesin (>99% purity) and 34 mg of aloeresin A (>98% purity) were recovered from 2.5 g of aloe juice. The HPLC method was validated, and intra- and interday performances were established. In-house validation was carried out by analyzing samples of beverages with and without aloe as a flavoring agent.
The Journal of Steroid Biochemistry and Molecular Biology, 2007
The conformational preferences of a group of 13-ethylsteroids and related estranes have been dete... more The conformational preferences of a group of 13-ethylsteroids and related estranes have been determined through theoretical calculations at the B3LYP/6-31G * level in order to ascertain differences and similarities in the conformational behavior which might, in principle, influence the activity. Attention was focussed on two geometrical features usually related to the progestational activity of this class of compounds, namely, the inversion of the A ring and the orientation of the 13-ethyl group. The present calculations show that the absence of the C10 methyl group, like in levonorgestrel, 3-ketodesogesterel, and gestodene, makes the inversion of the A ring easier than in norethisterone and ethisterone even if in any case the 1␣,2-half-chair conformation remains preferred. The preference of the ethyl group for the trans orientation is maintained by all the 13-ethylprogestogens though in gestodene also the g + gauche conformation is significantly populated. This preference was experimentally supported through a high field NMR spectroscopy study of the ethylsteroids.
The synthetic antithrombotic argatroban is a dipeptide between the nonproteogenic (2R,4R)-4-methy... more The synthetic antithrombotic argatroban is a dipeptide between the nonproteogenic (2R,4R)-4-methyl-2piperidine carboxylic acid and L-arginine, in turn bonded to a methyltetrahydroquinoline sulfonyl group. An extensive screening of transition metal-based complexes with different ligands was performed in order to identify the best catalyst for the diastereoselective hydrogenation of a suitable 4,5-dehydropiperidine precursor aimed toward a synthesis of the (2R,4R)-4-methyl piperidine moiety.
Abstmc f-The reduction of the 2-keto acetals la and lb by means of different microorganisms const... more Abstmc f-The reduction of the 2-keto acetals la and lb by means of different microorganisms constitutes the biocatalytic access to optically active (46 to 10% ee) 2-hydroxy acetals, (S)-2a or (R)and (S)-2b, representative compounds of a class of synthetically useful chiral building blocks.
A series of steroidal compounds were synthesized in order to evaluate the possible influence of t... more A series of steroidal compounds were synthesized in order to evaluate the possible influence of the configuration of a stereocenter in the 17-side chain on the inhibitory activity on the enzyme 5␣-reductase (5AR). For this purpose diastereomerically pure 4-azasteroids epimers at C-22 were prepared (compounds 1-11) and tested as inhibitors of 5AR in 'in vitro' tests. The obtained data showed that in most cases the couples of epimers possess a significant difference in their biological activity. We also considered, for the tested molecules, a series of chemico-physical parameters in order to find a possible correlation with their biological activity. The findings allowed us to propose a model of the binding site of 5AR which comprises also, for 4-azasteroid inhibitors, the configurational aspect of the 17-side chain.
A facile method for the synthesis of a series of new steroidal 3-thioxamides from the 3-0~0 compo... more A facile method for the synthesis of a series of new steroidal 3-thioxamides from the 3-0~0 compound, variously substituted at the I7 position, is described. The "one pot" reaction, using Lawesson's reagent (4methoxyphenylthionophosphine sulphide dimer) in dichloromethane solution, gives the desired compounds with a high degree of chemoselectivity, in good yields (>80%).
To determine whether the ability of testosterone to increase intrahypothalamic LH-releasing hormo... more To determine whether the ability of testosterone to increase intrahypothalamic LH-releasing hormone (LHRH) in orchidectomized rats might be explained by the conversion of the hormone into either its 5α-reduced or oestrogenic metabolites, testosterone, 5α-androstan-17β-ol-3-one (DHT), 5α-androstane-3α, 17β-diol (3α-diol) and 5α-androstane-3β,17β-diol (3β-diol) (2 mg/rat per day for 6 days) and oestradiol (0·1, 0·5, 1·0 and 5·0 μg/rat per day for 6 days) were injected into castrated male rats. After 6 days the rats were killed and serum LH levels and intrahypothalamic LHRH stores measured using specific radioimmunoassay procedures. Testosterone and its 5α-reduced metabolites were used in either the free alcohol or the propionate form (dipropionates in the case of the diols); oestradiol was used as oestradiol-17β or in the benzoate form. Treatment with testosterone, DHT, 3α-diol and 3β-diol resulted in a significant decrease in serum LH levels; all the 5α-reduced testosterone derivativ...
The synthesis of 2-morpholinoethyl mycophenolate was realized by an enzymatic transesterification... more The synthesis of 2-morpholinoethyl mycophenolate was realized by an enzymatic transesterification of simple esters of mycophenolic acid with 2-morpholinoethanol. Best results were achieved by a Candida antarctica lipase B (CAL B) catalyzed transesterification of ethyl mycophenolate in toluene. CAL B showed to selectively transform only the ethyl ester function leaving unreacted the other functional groups present on the substrate. By this way 2-morpholinoethyl mycophenolate was obtained in satisfactory yields from mycophenolic acid (84%).
... Enzymatic Resolution of 2-Substituted Oxiranemethanols, a Class of Synthetically Useful Build... more ... Enzymatic Resolution of 2-Substituted Oxiranemethanols, a Class of Synthetically Useful Building Blocks Bearing a Chiral Quaternary Center' Patrizia Ferraboschi, Daria Brembilla, Paride Grisenti, and Enzo Santaniello* ... 3 2 1 a. R=CH,C6H, b. R=CgHIg Scheme 111 Scheme IV ...
ChemInform AbstractÖstron (I) liefert bei der Nitrierung mit dem N-Nitropyrazol (II) im wesentlic... more ChemInform AbstractÖstron (I) liefert bei der Nitrierung mit dem N-Nitropyrazol (II) im wesentlichen die beiden Nitro-Verbindungen (IIIa) und (IIIb), während unter drastischeren Bedingungen, speziell mit rauchender Salpetersäure, auch das Dinitro-Derivat (IIIc) erhalten wird. (IR-, NMR-, MS-Daten).
The bioreductions mediated by BY and other microorganisms are considered mainly from a preparativ... more The bioreductions mediated by BY and other microorganisms are considered mainly from a preparative point of view. The use of other microorganisms is reported when BY is either unable to perform the reaction or if this proceeds with moderate enantioselectivity or when the opposite stereochemical outcome of the reaction should be obtained. The biotransformation of nitrogen-containing groups is especially addressed. The bioreductions of trinitrotoluene is presented as an example of the bioremediation of explosives.
Bioorganic Chemistry in Healthcare and Technology, 1991
The enzyme catalyzed transesterification of racemic alcohols has been recently introduced for the... more The enzyme catalyzed transesterification of racemic alcohols has been recently introduced for the preparation of enantiomerically pure alcohols and esters of opposite configurations [1], This procedure makes use of lipases from different sources as the biocatalysts and vinyl esters as acyl donors. The peculiarity of the method resides in the fact that the transesterification is irreversible, since one of the products, namely vinyl alcohol, rapidly tautomerizes to acetaldehyde and this prevents the back reaction. Further, the reaction can be efficiently carried out in organic solvents (Eq. 1).
The Pseudomonas fluorescens (P. cepacia) lipase-catalyzed irreversible transesterification of 2-p... more The Pseudomonas fluorescens (P. cepacia) lipase-catalyzed irreversible transesterification of 2-phenyl-1.2~propanediol la is not enantioselective, whereas the dials lb and lc am enzymatically resolved with the same procedure to (S)-lb and lc (>98 and 92% e.e.) and the (R)-acetates 2b and 2c (92% e.e.).
Reaction of Glycidyl p-Nitrobenzoate with Et2A1CN.'O To a solution of glycidyl p-nitrobenzoate (3... more Reaction of Glycidyl p-Nitrobenzoate with Et2A1CN.'O To a solution of glycidyl p-nitrobenzoate (34 mg, 0.15 mmol, racemic mixture) in toluene (5 mL) was added Et2A1CN (1.5 M solution in toluene, Alfa, 0.1 mL, 0.15 mmol) at room temperature. After 5 min, the homogeneous yellow solution was diluted with ether (30 mL) and then washed with 10% H2SO4, saturated NaHC03,
This work describes a sensitive high-performance liquid chromatography (HPLC) method for the quan... more This work describes a sensitive high-performance liquid chromatography (HPLC) method for the quantification of aloesin and aloeresin A in alcoholic beverages containing aloe as a flavoring agent. The compounds were prepared from Aloe ferox juice. Sephadex LH20 and ion-exchange resin AG1X2 column chromatography were used for aloesin. Aloeresin A was obtained by Sephadex LH20 and silica gel column chromatography followed by purification on Discovery DSC-18 solid-phase extraction tubes. A 98 mg amount of aloesin (>99% purity) and 34 mg of aloeresin A (>98% purity) were recovered from 2.5 g of aloe juice. The HPLC method was validated, and intra- and interday performances were established. In-house validation was carried out by analyzing samples of beverages with and without aloe as a flavoring agent.
The Journal of Steroid Biochemistry and Molecular Biology, 2007
The conformational preferences of a group of 13-ethylsteroids and related estranes have been dete... more The conformational preferences of a group of 13-ethylsteroids and related estranes have been determined through theoretical calculations at the B3LYP/6-31G * level in order to ascertain differences and similarities in the conformational behavior which might, in principle, influence the activity. Attention was focussed on two geometrical features usually related to the progestational activity of this class of compounds, namely, the inversion of the A ring and the orientation of the 13-ethyl group. The present calculations show that the absence of the C10 methyl group, like in levonorgestrel, 3-ketodesogesterel, and gestodene, makes the inversion of the A ring easier than in norethisterone and ethisterone even if in any case the 1␣,2-half-chair conformation remains preferred. The preference of the ethyl group for the trans orientation is maintained by all the 13-ethylprogestogens though in gestodene also the g + gauche conformation is significantly populated. This preference was experimentally supported through a high field NMR spectroscopy study of the ethylsteroids.
The synthetic antithrombotic argatroban is a dipeptide between the nonproteogenic (2R,4R)-4-methy... more The synthetic antithrombotic argatroban is a dipeptide between the nonproteogenic (2R,4R)-4-methyl-2piperidine carboxylic acid and L-arginine, in turn bonded to a methyltetrahydroquinoline sulfonyl group. An extensive screening of transition metal-based complexes with different ligands was performed in order to identify the best catalyst for the diastereoselective hydrogenation of a suitable 4,5-dehydropiperidine precursor aimed toward a synthesis of the (2R,4R)-4-methyl piperidine moiety.
Abstmc f-The reduction of the 2-keto acetals la and lb by means of different microorganisms const... more Abstmc f-The reduction of the 2-keto acetals la and lb by means of different microorganisms constitutes the biocatalytic access to optically active (46 to 10% ee) 2-hydroxy acetals, (S)-2a or (R)and (S)-2b, representative compounds of a class of synthetically useful chiral building blocks.
A series of steroidal compounds were synthesized in order to evaluate the possible influence of t... more A series of steroidal compounds were synthesized in order to evaluate the possible influence of the configuration of a stereocenter in the 17-side chain on the inhibitory activity on the enzyme 5␣-reductase (5AR). For this purpose diastereomerically pure 4-azasteroids epimers at C-22 were prepared (compounds 1-11) and tested as inhibitors of 5AR in 'in vitro' tests. The obtained data showed that in most cases the couples of epimers possess a significant difference in their biological activity. We also considered, for the tested molecules, a series of chemico-physical parameters in order to find a possible correlation with their biological activity. The findings allowed us to propose a model of the binding site of 5AR which comprises also, for 4-azasteroid inhibitors, the configurational aspect of the 17-side chain.
A facile method for the synthesis of a series of new steroidal 3-thioxamides from the 3-0~0 compo... more A facile method for the synthesis of a series of new steroidal 3-thioxamides from the 3-0~0 compound, variously substituted at the I7 position, is described. The "one pot" reaction, using Lawesson's reagent (4methoxyphenylthionophosphine sulphide dimer) in dichloromethane solution, gives the desired compounds with a high degree of chemoselectivity, in good yields (>80%).
To determine whether the ability of testosterone to increase intrahypothalamic LH-releasing hormo... more To determine whether the ability of testosterone to increase intrahypothalamic LH-releasing hormone (LHRH) in orchidectomized rats might be explained by the conversion of the hormone into either its 5α-reduced or oestrogenic metabolites, testosterone, 5α-androstan-17β-ol-3-one (DHT), 5α-androstane-3α, 17β-diol (3α-diol) and 5α-androstane-3β,17β-diol (3β-diol) (2 mg/rat per day for 6 days) and oestradiol (0·1, 0·5, 1·0 and 5·0 μg/rat per day for 6 days) were injected into castrated male rats. After 6 days the rats were killed and serum LH levels and intrahypothalamic LHRH stores measured using specific radioimmunoassay procedures. Testosterone and its 5α-reduced metabolites were used in either the free alcohol or the propionate form (dipropionates in the case of the diols); oestradiol was used as oestradiol-17β or in the benzoate form. Treatment with testosterone, DHT, 3α-diol and 3β-diol resulted in a significant decrease in serum LH levels; all the 5α-reduced testosterone derivativ...
The synthesis of 2-morpholinoethyl mycophenolate was realized by an enzymatic transesterification... more The synthesis of 2-morpholinoethyl mycophenolate was realized by an enzymatic transesterification of simple esters of mycophenolic acid with 2-morpholinoethanol. Best results were achieved by a Candida antarctica lipase B (CAL B) catalyzed transesterification of ethyl mycophenolate in toluene. CAL B showed to selectively transform only the ethyl ester function leaving unreacted the other functional groups present on the substrate. By this way 2-morpholinoethyl mycophenolate was obtained in satisfactory yields from mycophenolic acid (84%).
... Enzymatic Resolution of 2-Substituted Oxiranemethanols, a Class of Synthetically Useful Build... more ... Enzymatic Resolution of 2-Substituted Oxiranemethanols, a Class of Synthetically Useful Building Blocks Bearing a Chiral Quaternary Center' Patrizia Ferraboschi, Daria Brembilla, Paride Grisenti, and Enzo Santaniello* ... 3 2 1 a. R=CH,C6H, b. R=CgHIg Scheme 111 Scheme IV ...
ChemInform AbstractÖstron (I) liefert bei der Nitrierung mit dem N-Nitropyrazol (II) im wesentlic... more ChemInform AbstractÖstron (I) liefert bei der Nitrierung mit dem N-Nitropyrazol (II) im wesentlichen die beiden Nitro-Verbindungen (IIIa) und (IIIb), während unter drastischeren Bedingungen, speziell mit rauchender Salpetersäure, auch das Dinitro-Derivat (IIIc) erhalten wird. (IR-, NMR-, MS-Daten).
The bioreductions mediated by BY and other microorganisms are considered mainly from a preparativ... more The bioreductions mediated by BY and other microorganisms are considered mainly from a preparative point of view. The use of other microorganisms is reported when BY is either unable to perform the reaction or if this proceeds with moderate enantioselectivity or when the opposite stereochemical outcome of the reaction should be obtained. The biotransformation of nitrogen-containing groups is especially addressed. The bioreductions of trinitrotoluene is presented as an example of the bioremediation of explosives.
Bioorganic Chemistry in Healthcare and Technology, 1991
The enzyme catalyzed transesterification of racemic alcohols has been recently introduced for the... more The enzyme catalyzed transesterification of racemic alcohols has been recently introduced for the preparation of enantiomerically pure alcohols and esters of opposite configurations [1], This procedure makes use of lipases from different sources as the biocatalysts and vinyl esters as acyl donors. The peculiarity of the method resides in the fact that the transesterification is irreversible, since one of the products, namely vinyl alcohol, rapidly tautomerizes to acetaldehyde and this prevents the back reaction. Further, the reaction can be efficiently carried out in organic solvents (Eq. 1).
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