Synthetic investigations in the sesamin group - Part I. Synthesis of samin, a degradation product of sesamolin

Ethylα-bromovinylacetate (VII) was condensed with the sodio derivative of ethyl piperonoylacetate (VIII) to give diethylα-vinyl-α′-piperonoylsuccinate (IX). The latter on reduction with lithium aluminium hydride furnished the triol (X), which underwent smooth cyclisation with 1% ethanolic hydrogen chloride to 2-(3′, -methylenedioxyphenyl)-hydroxymethyl-4-vinyltetrahydrofuran (XIa). The structure of XIa was established by Oppenauer oxidation to an aldehyde. Ozonolysis of XIa afforded samin (I).

Role of the leaving group in the base-catalysed hydrolysis of pseudo-esters

The relative insensitivity of the rate of hydrolysis of γ-pseudo-esters to the leaving group compared to that of the normal esters emphasises that the conjugative ability is an important factor in determining the rate of hydrolysis of esters

Hydrolytic reactions of esters and amides of thiosulphurous acid in a homogeneous medium

The hydrolytic reactions of esters and amides of thiosulphurous acid are investigated in a homogeneous medium. The esters are hydrolysed by alkali to give sulphide, sulphite and thiosulphate whereas the amides are resistant towards alkali. Both the esters and amides are hydrolysed by acids giving hydrogen sulphide, sulphur dioxide, polythionates and elemental sulphur. The hydrolysis of these esters and amides in presence of sulphurous acid and thiosulphuric acid gives tetrathionate and hexathionate, respectively.

High cholesterol diet and esterification of cholesterol by the intestinal mucosa of rats

Young male rats maintained on a diet containing 1% cholesterol were sacrificed at the end of 1st, 2nd, 3rd, 5th, and 7th week. Acetone powders prepared from their intestinal mucosa and pancreas were tested for the synthetic and hydrolytic activities for Vitamin A and cholesterol esters. The esterifying activity of the mucosal enzymes for both Vitamin A and cholesterol increased progressively up to the end of the 5th week; the increase in esterification of cholesterol was more marked with respect to saturated fatty acids, as compared to the unsaturated ones. The pancreatic enzymes remained unaffected. It is suggested that one of the reasons for the accumulation of cholesterol esters in animal tissues may be the increased esterification of the sterol in the mucosa induced by dietary cholesterol.

Synthetic investigation on the building of ring A of steroids

Methyl 7-keto-1,2,3,4,4a,5,6,7-octahydronaphthoate (Va) has been prepared by the reduction of 7-methoxy-1,2,3,4-tetrahydronaphthoic acid (III) with lithium and ammonia followed by hydrolysis of the enol ether, esterification and migration of the double bond. Alkylation of Va has led to the substitution at the expected 8-position. Methyl 4-keto-7-methoxy-1,2,3,4-tetrahydronaphthoate (X), an intermediate in the preparation of III, has been converted into methyl 3-methyl-3-cyano-4-keto-7-methoxy-1,2,3,4-tetrahydronaphthoate (XIII).

Isomerisations of substituted β-keto-esters - Part II. Isomerisation of ethyl 1-ethoxycarbonyl 2oxocyclopentyl acetate into 2, 3-diethoxycarbonylcyclohexanone

A mechanism for the isomerisation of ethyl 1-ethoxycarbonyl-2-oxocyclopentylacetate (I) into a cyclohexane β-keto-ester as proceeding through an intermediate bicyclic /gb-diketone (VII) has been considered as an alternative mechanism to one earlier suggested.1 The determination of the structure of the isomerised β-keto-ester as 2, 3-diethoxycarbonylcyclohexanone (V) has provided support for the earlier mechanism.

An unusual C-H center dot center dot center dot O hydrogen bond mediated reversal of polypeptide chain direction in a synthetic peptide helix

An unusual C-terminal conformation has been detected in a synthetic decapeptide designed to analyze the stereochemistry of helix termination in polypeptides. The crystal structure of the decapeptide Boc-Leu-Aib-Val-Ala-Leu-Aib-Val-(D)Ala-(D)Leu-Aib-OMe reveals a helical segment spanning residues 1-7 and helix termination by formation of a Schellman motif, generated by (D)Ala(8) adopting the left-handed helical (alpha(L)) conformation. The extended conformation at (D)Leu(9) results in a compact folded structure, stabilized by a potentially strong C-H ... O hydrogen bond between Ala(4) (CH)-H-alpha and (D)Leu(9)CO. The parameters for C-H ... O interaction are Ala(4) (CH)-H-alpha .. O=C (D)Leu(9) distance 3.27 Angstrom C-alpha-H .. O angle 176 degrees, and O .. H-alpha distance 2.29 Angstrom. This structure suggests that insertion of contiguous D-residues may provide a handle for the generation of designed structures containing more than one helical segment folded in a compact manner. (C) 2000 Academic Press.

A Novel Synthetic Route For The Preparation Of Ammonium And Alkali-Metal Tetrafluoroborates And Alkyl Substituted Ammonium Tetrafluoroborates Using Pyridinium Tetrafluoroborate As The Precursor

Ammonium and alkali metal tetrafluoroborates have been prepared by the cation exchange reaction of pyridinium tetrafluoroborate with the corresponding hydroxides/halides. The reaction of pyridinium tetrafluoroborate with primary, secondary and tertiary alkyl amines at room temperature gives rise to mono-, di- and tri-alkylammonium tetrafluoroborates, respectively. The yields are good and the samples are of high purity. The products have been characterised by elemental analysis, IR and PMR spectroscopy. The spectral data for most of the compounds are reported for the first time.

A Novel Synthetic Route for the Preparation of Silver Salts of Hexafluorophosphate, Tetrafluoroborate and Hexafluorosilicate

Silver salts of hexafluorophosphates, tetrafluoro-borates and hexafluorosilicates have been prepared by a metathetic reaction between the respective ammonium salts and silver nitrate in acetonitrile medium. This one step procedure at room temperature offers salts of high purity in good yields. The salts (AgpF6, AgBF4 and Ag2SiF6) have been characterised by IR spectral data analysis and chemical analysis.

Hydrolysis of Organophosphate Esters: Phosphotriesterase Activity of Metallo-beta-lactamase and Its Functional Mimics

The phosphotriesterase (PTE) activity of a series of binuclear and mononuclear zinc(II) complexes and metallo-beta-lactamase (m beta 1) from Bacillus cereus was studied. The binuclear complex 1, which exhibits good m beta 1 activity, shows poor PTE activity. In contrast,complex 2, a poor mimic of m beta 1, exhibits much higher activity than 1 The replacement of Cl- ligands by OH- is important for the high PTE activity of complex 2 because this complex does not show any catalytic activity in methanol. The natural enzyme m beta 1 from B. cereus is also found to be an inefficient catalyst in the hydrolysis of phosphotriesters. These observations indicate that the binding of beta-lactam substrates at the binuclear zinc(II) center is different from that of phosphotriesters. Furthermore, phosphodiesters, the products from the hydrolysis of triesters, significantly inhibit the PTE activity of m beta 1 and its functional mimics. Although the mononuclear complexes 3 and 4 exhibited significant m beta 1 activity, these complexes are found to be almost inactive in the hydrolysis of phosphotriesters. These observations indicate that the elimination of phosphodiesters from the reaction site is important for the PTE activity of zinc(II) complexes.

Assessment of In-House Natural Product and Synthetic Compound Libraries Based on In vitro Inhibition of Cholinesterases

The first line medication for mild to moderate Alzheimer s disease (AD) is based on cholinesterase inhibitors which prolong the effect of the neurotransmitter acetylcholine in cholinergic nerve synapses which relieves the symptoms of the disease. Implications of cholinesterases involvement in disease modifying processes has increased interest in this research area. The drug discovery and development process is a long and expensive process that takes on average 13.5 years and costs approximately 0.9 billion US dollars. Drug attritions in the clinical phases are common due to several reasons, e.g., poor bioavailability of compounds leading to low efficacy or toxic effects. Thus, improvements in the early drug discovery process are needed to create highly potent non-toxic compounds with predicted drug-like properties. Nature has been a good source for the discovery of new medicines accounting for around half of the new drugs approved to market during the last three decades. These compounds are direct isolates from the nature, their synthetic derivatives or natural mimics. Synthetic chemistry is an alternative way to produce compounds for drug discovery purposes. Both sources have pros and cons. The screening of new bioactive compounds in vitro is based on assaying compound libraries against targets. Assay set-up has to be adapted and validated for each screen to produce high quality data. Depending on the size of the library, miniaturization and automation are often requirements to reduce solvent and compound amounts and fasten the process. In this contribution, natural extract, natural pure compound and synthetic compound libraries were assessed as sources for new bioactive compounds. The libraries were screened primarily for acetylcholinesterase inhibitory effect and secondarily for butyrylcholinesterase inhibitory effect. To be able to screen the libraries, two assays were evaluated as screening tools and adapted to be compatible with special features of each library. The assays were validated to create high quality data. Cholinesterase inhibitors with various potencies and selectivity were found in natural product and synthetic compound libraries which indicates that the two sources complement each other. It is acknowledged that natural compounds differ structurally from compounds in synthetic compound libraries which further support the view of complementation especially if a high diversity of structures is the criterion for selection of compounds in a library.

Flame retardant polyphosphate esters: 1. Condensation polymers of bisphenols with aryl phosphorodichloridates: synthesis, characterization and thermal studies

Polyphosphate esters were synthesized by the solution polycondensation of bisphenols with aryl phosphorodichloridates. The polymers were characterized by i.r. and 1H, 13C and 31P n.m.r. spectroscopy. The molecular weights were determined by end group analysis using 1H and 31P n.m.r. spectral data. The thermal stability of the polymers was analysed by thermogravimetry.