Microbial Transformation of Sesquiterpenes, (−)‐Ambrox® and (+)‐Sclareolide

The microbial transformation of (?)‐Ambrox^® ( 1 ), a perfumery sesquiterpene, by a number of fungi, by means of standard two‐stage‐fermentation technique, afforded ambrox‐1α‐ol ( 2 ), ambrox‐1α,11α‐diol ( 3 ), ambrox‐1α,6α‐diol ( 4 ), ambrox‐1α,6α,11α‐triol ( 5 ), ambrox‐3‐one ( 6 ), ambrox‐3β‐ol ( 7 ), ambrox‐3β,6β‐diol ( 8 ), 13,14,15,16‐tetranorlabdane‐3,8,12‐triol ( 9 ), and sclareolide ( 10 ) (Schemes 1 and 2). Further incubation of compound 10 with Cunninghamella elegans afforded 3‐oxosclareolide ( 11 ), 3β‐hydroxysclareolide ( 12 ), 2α‐hydroxysclareolide ( 13 ), 2α,3β‐dihydroxysclareolide ( 14 ), 1α,3β‐dihydroxysclareolide ( 15 ), and 3β‐hydroxy‐8‐episclareolide ( 16 ) (Scheme 3). Metabolites 2 – 5, 12, 13 , and 16 were found to be new compounds. The major transformations include a reaction path involving hydroxylation, ether‐bond cleavage and inversion of configuration. Metabolites 11 – 16 of sclareolide showed significant phytotoxicity (Table 1). The structures of the metabolites were characterized on the basis of spectroscopic techniques.     

Microbial transformation of prednisone

The microbial transformation of prednisone (17alpha,21-dihydroxy-pregna-1,4-diene-3,11,20-trione) (1) by Cunninghamella elegans afforded two metabolites, 17alpha,21-dihydroxy-5alpha-pregn-1-ene-3,11,20-trione (2) and 17alpha,20S,21-trihydroxy-5alpha-pregn-1-ene-3,11-dione (3), while the fermentation of 1 with Fusarium lini, Rhizopus stolonifer and Curvularia lunata afforded a metabolite 1,4-pregnadiene-17alpha,20S,21-triol-3,11-dione (4). Compound 3 was found to be a new metabolite. Their structures were elucidated on the basis of spectroscopic techniques. Compound 3 showed inhibitory activity against lipoxygenase enzyme.     

Relative magnitudes of singlet and triplet state dipole moments: the lowest nπ* excited states of p-methylbenzaldehyde and p-chlorobenzaldehyde

The molecular dipole moment changes upon ¹nπ* and ³nπ* excitation of p-methylbenzaldehyde and p-chlorobenzaldehyde isolated in p-dimethoxybenzene host crystals have been determined from measurements of the Stark splittings in phosphorescence excitation and phosphorescence spectra. Within the experimental uncertainty, the changes are identical for the corresponding triplet and singlet states. This result contrasts with similar determinations for formaldehyde, benzophenone, and 4,4′-dichlorobenzophenone and with predictions based on simple molecular orbital and electron correlation arguments. The result is considered to be a consequence of a relatively large mixing of ³nμ* and ³μμ* states.     

Validated TLC-densitometry method for the simultaneous analysis of pyrethroid insecticides in agricultural and domestic products

ABSTRACT: BACKGROUND: Pyrethroids are widely used for the control of pests and insects, as pyrethroids are believed to pose very little risk to human health and environment. However, exposure to the pyrethroids exceeding the label directions might adversely affect human health and environment. Hence a careful selection of environment friendly household product is required that must contain exactly the label claimed pyrethroids amount. RESULTS: A sensitive and robust TLC-densitometric method for simultaneous quantification of commonly used synthetic pyrethroids including esbiothrin, alpha-cypermethrin and cis/trans permethrin in agricultural and domestic products has been developed and validated. TLC aluminum plates, precoated with 0.2 mm thick layer of silica gel 60 F-254, were used for chromatographic process. Densitometric analysis of chromatoplates was carried out in absorbance mode at corresponding lamdamax of each pyrethroid. Equally valid common mobile phase for all pyrethroids consisted of hexane-dichloromethane-ethylacetate-formic acid (8:1.5:0.4:0.1 v/v/v/v) which provided sharp and symmetrical peaks of esbiothrin, alpha-cypermethrin, trans-permethrin and cis-permethrin, at Rf 0.31, 0.53, 0.6 and 0.65, respectively. Linear regression data for respective calibration curves showed a good linearity for all pyrethroids with r = 0.991-0.996. Limits of detection (LOD) and limits of quantification (LOQ) for all pyrethroids were found in the range of 1.6-2.8 and 4.9-8.5 ng/spot, respectively. CONCLUSIONS: The developed method is applicable for separating the mixture of pyrethroids and at the same time, it is also valid for separating their isomers. The method is reproducible, precise and accurate for the quantitative determination of pyrethroids in agricultural and domestic products.     

Synthesis and Characterization of Novel Biodegradable Di‐ and Tri‐Block Copolymers Based on Ethylene Carbonate Polymer as Hydrophobic Segment

Synthesis of novel amphiphilic biodegradable block copolymers based on ethylene carbonate is reported in this study. Polyethylene glycol monomethyl ether (MeO‐PEO) and polyethylene glycol (PEG) of varying molar masses are used as macro‐initiator for ring‐opening polymerization of ethylene carbonate in the presence of sodium stannate trihydrate as a heterogeneous transesterification catalyst. Earlier elution of block copolymer from macro‐initiator in size exclusion chromatography (SEC) indicated the successful synthesis of the block copolymers. Ratios of both types of blocks are varied systematically. Liquid chromatography at critical conditions is used for the analysis of the non‐critical individual blocks, and if there are any critical segments that are not attached to the non‐critical block. To the best of our knowledge, this is the first report on the synthesis of ethylene carbonate‐based amphiphilic block copolymers. Chromatographic critical conditions of the ethylene carbonate polymer are also reported for the first time. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017 , 55, 1887–1893     

Microbial transformation of mestranol by Cunninghamella elegans

The microbial transformation of an oral contraceptive, mestranol (1) by Cunninghamella elegans yielded two hydroxylated metabolites, 6beta-hydroxymestranol (2) and 6beta,12beta-dihydroxymestranol (3). Metabolite 3 was found to be a new compound. These metabolites were structurally characterized on the basis of spectroscopic techniques.     

Microbial transformation of dehydroepiandrosterone

Transformation of dehydroepiandrosterone (DHEA) (1) was carried out by a plant pathogen Rhizopus stolonifer, which resulted in the production of seven metabolites. These metabolites were identified as 3beta,17beta-dihydroxyanandrost-5-ene (2), 3beta,17beta-dihydroxyandrost-4ene (3), 17beta-hydroxyandrost-4-ene-3-one (4), 3beta,11-dihydroxyandrost-4-ene-17-one (5), 3beta,7alpha-dihydroandrost-5-ene-17-one (6), 3A,7alpha,17beta-trihydroxyandrost-5-ene (7) and 11beta-hydroxyandrost-4,6-diene-3,17-dione (8). The structures of the transformed products were determined by the spectroscopic techniques.     

Analysis and development of structure-fragmentation relationships in withanolides using an electrospray ionization quadropole time-of-flight tandem mass spectrometry hybrid instrument

Structural elucidation and gas‐phase fragmentation of ten withanolides (steroidal lactones) were studied using a positive ion electrospray ionization quadropole time‐of‐flight mass spectrometry (ESI‐QqTOF‐MS/MS) hybrid instrument. Withanolides form an important class of plant secondary metabolites, known to possess a variety of biological activities. Withanolides which possess hydroxyl groups at C‐4, C‐5, C‐17, C‐20, and C‐27, and an epoxy group at C‐5/C‐6, were evaluated to determine the characteristic fragments and their possible pathways. ESI‐QqTOF‐MS (positive ion mode) showed the presence of the protonated molecules [M + H]⁺. Low‐energy collision‐induced dissociation tandem mass spectrometric (CID‐MS/MS) analysis of the protonated molecule [M + H]⁺ indicated multiple losses of water and the removal of the C‐17‐substituted lactone moiety affording the [M + H–Lac]⁺ product ion as the predominant pathways. However, withanolides containing a hydroxyl group at C‐24 of the lactone moiety showed a different fragmentation pathway, which include the loss of steroidal part as a neutral molecule, with highly diagnostic ions at m/z 95 and 67 being generated from the cleavage of lactone moiety. Our results also determined the influence of the presence and positions of hydroxyl and epoxy groups on product ion formation and stability. Moreover, the knowledge of the fragmentation pattern was utilized in rapid identification of withanolides by the LC/MS/MS analysis of a Withania somnifera extract. Copyright © 2010 John Wiley & Sons, Ltd.     

Development and Validation of TLC—Densitometric Method for the Quantification of a Steroidal Drug,Danazol in its Pharmaceutical Formulations

JPC – Journal of Planar Chromatography – Modern TLC - A reliable and sensitive thin-layer chromatographic (TLC)-densitometric method is developed for the analysis of danazol in its...     

Stress degradation studies and development of stability-indicating TLC-densitometry method for determination of prednisolone acetate and chloramphenicol in their individual and combined pharmaceutical formulations

ABSTRACT: A rapid and reproducible stability indicating TLC method was developed for the determination of prednisolone acetate and chloramphenicol in presence of their degraded products. Uniform degradation conditions were maintained by refluxing sixteen reaction mixtures for two hours at 80°C using parallel synthesizer including acidic, alkaline and neutral hydrolysis, oxidation and wet heating degradation. Oxidation at room temperature, photochemical and dry heating degradation studies were also carried out. Separation was done on TLC glass plates, pre-coated with silica gel 60F-254 using chloroform: methanol (14:1 v/v). Spots at Rf 0.21 ± 0.02 and Rf 0.41 ± 0.03 were recognized as chloramphenicol and prednisolone acetate, respectively. Quantitative analysis was done through densitometric measurements at multiwavelength (243 nm, λmax of prednisolone acetate and 278 nm, λmax of chloramphenicol), simultaneously. The developed method was optimized and validated as per ICH guidelines. Method was found linear over the concentration range of 200-6000 ng/spot with the correlation coefficient (r2 ± S.D.) of 0.9976 ± 3.5 and 0.9920 ± 2.5 for prednisolone acetate and chloramphenicol, respectively. The developed TLC method can be applied for routine analysis of prednisolone acetate and chloramphenicol in presence of their degraded products in their individual and combined pharmaceutical formulations.