Induction of Wavelength Dependent Photochemistry in Bilirubins by SerumAlbumin [1]: A Comment

Summary.  The article cited in the title [1] did not take into account the probability of occupation of the excition (Davidoff) states by the different chromophores of the bilirubins, as is determined by the necessary quantum mechanics. Since this probability is intrinsically wavelength dependent, the discussion in the mentioned paper should be extended with respect to this effect. Received November 29, 1999. Accepted December 13, 1999     

Concerning the Association of Hypericin Tautomers and their Hypericinate Ions

Summary.  The association of the like and unlike configured propeller and butterfly conformers of unionized and bay-ionized 7,14-, 1,6-, and 1,7-tautomers of hypericin was investigated by means of semiempirical calculations of the MM3 type. From the various possible stack dimers it was found that the homodimer with like configurations of the propeller conformations of unionized hypericin was the most stable one, making them strongly stabilized over any coplanar arrangements. Oligomerization led to further stabilization of the stacked homoassociates up to five units. Adding more units did not lead to further stabilization. Accordingly, dispersion forces between the aromatic systems dominate in associate stabilization, with hydrogen bonding playing a marginal role only. These findings were compared with the rather scarce experimental evidence. Received October 27, 1999. Accepted December 3, 1999     

Synthesis of Structurally Related Purines: Benzimidazo[1,2-a]pyridines, Benzimidazo-[1,2-c]pyrimidines, and Pyrazolo-[1,5-a]pyrimidines

Summary.  Reactions of sodium salts of 3-hydroxymethylene-2-alkanones with 2-cyanomethylbenzimidazole afforded benzimidazo[1,2-a]pyridines. Analogues reactions with 2-aminobenzimidazole and 5-aminopyrazoles afforded benzimidazo[1,2-c]pyrimidines and pyrazolo[1,5-a]pyrimidines. Received December 12, 1999. Accepted (revised) February 12, 2000     

Kinetics of the Oxidative Degradation of rac-Serine by Aqueous Alkaline Permanganate

Summary.  The kinetics of the oxidation of rac-serine by permanganate in aqueous alkaline medium was studied spectrophotometrically. The reaction showed first order kinetics in permanganate ion concentration and an order less than unity in rac-serine and alkali concentration. Increasing ionic strength and decreasing dielectric constant of the medium increase the rate. The oxidation reaction proceeds via an alkali-permanganate species which forms a complex with rac-serine. The latter decomposes slowly, followed by a fast reaction between a free radical of rac-serine and another molecule of permanganate to give the products. There is a good agreement between the observed and the calculated rate constants under different experimental conditions. Investigations at different temperatures allowed the determination of the activation parameters with respect to the slow step of the proposed mechanism. Received October 15, 1999. Accepted (revised) December 15, 1999     

Synthesis of Pyrazoles from 1-Acylmethylene-3,3-dimethyl-1,3-dihydroisobenzofurans

Summary.  1-Acylmethylene-3,3-dimethyl-1,3-dihydroisobenzofurans were found to be useful precursors for pyrazole synthesis. In the reaction with hydrazine monohydrate they yielded 3-(2-(α-hydroxyisopropyl)-phenyl) substituted NH-pyrazoles, whereas using alkyl- or arylhydrazine gave access to 5-(2-(α-hydroxyisopropyl)-phenyl) substituted NR-pyrazoles with good regioselectivity. Treatment with orthophosphoric acid led to C,N-fused and C,C-fused pyrazoles, respectively. Received November 4, 1999. Accepted (revised) December 3, 1999     

Beauveria bassiana ATCC 7159 Containsan L-Specific a-Amino Acid Benzamidase

Summary.  Biotransformation of a series of racemic N-benzoyl α-amino acids by the fungus Beauveria bassiana ATCC 7159 results in isolation of the corresponding D-amino acid benzamides in high enantiomeric purity and yield. Received December 20, 1999. Accepted January 21, 2000     

Sterically Controlled Regiospecific Cyclization of Aldose-5-ethyl-1,2,4-triazino[5,6-b]indol-3-ylhydrazones to Linearly Annelated 3-Polyhydroxyalkyl-10-ethyl-1,2,4-triazolo-[4′,3′:2,3]-1,2,4-triazino[5,6-b]indoles

Summary.  Condensation of aldoses with 5-ethyl-3-hydrazino-1,2,4-triazino[5,6-b ]indole gave the corresponding aldose-5-ethyl-1,2,4-triazino[5,6-b ]indol-3-ylhydrazones which were acetylated to their poly-O-acetyl derivatives. The latter underwent sterically controlled regiospecific oxidative cyclization with bromine in acetic acid and sodium acetate to sterically favourable linearly annelated 3-polyacetoxyalkyl-10-ethyl-1,2,4-triazole[4′,3′:2,3]-1,2,4-triazino[5,6-b ]indoles rather than to their sterically unfavourable angularly annelated regioisomers. The regiospecific outcome of this heterocyclization is discussed in terms of electronic as well as steric factors, and the assigned structures have been corroborated on the basis of chemical as well as spectroscopic evidence. De-O-acetylation of the acetoxyindoles with ammonium hydroxide in methanol gave the title compounds. Representative members of the prepared compounds were tested for antimicrobial activity. Received November 3, 1999. Accepted December 13, 1999     

Crystal Structure and Conformation of a Dipyrrylmethane. The gem-Dimethyl Effect

Summary.  A crystal structure determination of the new dipyrrylmethane diethyl-2,3,5,5,7,8-hexamethyl-5,10-dihydrodipyrrin-1,9-dicarboxylate (1) is only the third reported for a dipyrrylmethane and the first with a gem-dimethyl group at the bridging carbon atom. Conformation determining torsion angles are compared to those from molecular mechanics calculations and to the corresponding data for an analogous dipyrrylmethane (2) with no gem-dimethyl moiety. The crystal structures of 1 and 2 differ significantly: 1 adopts the +ac,+ac or −ac,−ac conformation, whereas 2 exists in the −ac,+sc conformation in an intermolecularly hydrogen bonded dimer. There is no evidence for hydrogen bonding in crystals of 1, and its ac conformation is unlike that found about the central core of bilirubin (sc,sc). Taken collectively, the data indicate that the presence of a sterically demanding and potentially conformation distorting gem-dimethyl group located at the bridging carbon of a dipyrrylmethane (i) stabilizes a conformation that brings the pyrrole NH groups syn to the gem-dimethyls and (ii) would destabilize the ridge-title conformation of 10,10-dimethylbilirubin. Received December 3, 1999. Accepted December 15, 1999     

An Unexpected Synthesis of Novel Oxygen-Bridged 1,5-Benzothiazepine Derivatives and their Reductive Five-Membered-Ring Opening

Summary.  A convenient procedure is reported for the preparation of benzofuro-annelated 2-phenyl-1,5-benzothiazepine derivatives by oxidative cyclocondensation of phenolic β-diketones with o-aminothiophenol in DMSO. The regiochemistry of these compounds is proven by HMBC signals and the existence of a five-bond ¹⁹F,¹³C-2 coupling. Surprisingly, treatment with LiAlH₄ at room temperature led to a double reduction under opening of the five-membered ring. Refluxing such solutions with a higher amount of LiAlH₄ gave rise to a further reduced derivative possessing the trans-configuration. All structures (regio- and stereochemistry) were assigned on the basis of NMR spectroscopic data. Received November 22, 1999. Accepted December 21, 1999     

Vanadophosphoric Acid as a Modified Reagent for the Spectrophotometric Determination of Certain Cephalosporins and their Dosage Forms

Summary.  Vanadophosphoric acid in acidic medium is proposed as a modified reagent for the spectrophotometric determination of cephalexin, cephaprine sodium, cefazolin sodium, and cefotaxime in pure samples and in pharmaceutical preparations. The method is based on acid hydrolysis of cephalosporins and subsequent oxidation with vanadophosphoric acid. The resulting solution exhibits maximum absorption at about 516 nm. The effects of reaction conditions were investigated. Lambert-Beer’s law was obeyed over a concentration range of about 0.4–45 μg · cm⁻³. For more accurate results, Ringbom optimum concentration ranges were obtained, and the molar absorptivities and Sandell sensitivities were derived. The proposed method was applied to the determination of the drugs in pharmaceutical formulations; the results demonstrated that the proposed method is as accurate, pecise, and reproducible as the official methods. Received August 13, 1999. Accepted (revised) December 7, 1999     

Immobilization of Rhodococcus AJ270 and Useof Entrapped Biocatalyst for the Productionof Acrylic Acid

Summary.  Rhodococcus AJ270 is adsorbed by Dowex 1 at 15.4  mg dry weight per g resin with maximum amidase specific activity observed at lower loadings. Bacteria form a monolayer on the resin surface, and adsorption is complete within 2 min. AJ270 can be entrapped in agar and agarose gels (optimum loading: 20 mg dry weight bacteria per cm³ gel). Adsorption and entrapment improve amidase thermal stability 3–4 fold, and entrapment shifts the pH optimum from 8 to 7. Adsorbed and free bacteria show similar values for K _m and V _max, but entrapped bacteria have higher K _m values. Compared with bacteria adsorbed to Dowex, the activity per cm³ of matrix of agar-entrapped AJ270 is eight-fold higher. In stirred-tank reactors, exposure to acrylic acid reduces the amidase activity of the biocatalyst in the hydrolysis of acrylamide. In column reactors, entrapped AJ270 suffers little reduction in amidase activity against 0.25 M acrylamide over 22 h continuous operation. Received November 18, 1999. Accepted December 14, 1999     

Lipase-Catalyzed Resolution of Ibuprofen

Summary.  The resolution of ibuprofen by transesterification of its corresponding vinylester using lipase B from Candida antarctica is described. Compared to transesterification or hydrolysis of the ibuprofen ethyl ester (E < 2, 28–48 h), the reaction with vinylesters occurred significantly faster (1.5–5 h) and with considerably higher enantioselectivity (E = 8–39). Received December 20, 1999. Accepted January 12, 2000     

Lipase-Catalyzed Synthesis of Carboxylic Amides: Nitrogen Nucleophiles as Acyl Acceptor

Summary.  The lipase-catalyzed aminolysis of carboxylic esters is a fairly general reaction that has been performed with a wide range of esters and amines, generally in anhydrous organic media to avoid undesirable hydrolysis of the ester. Alternatively, carboxylic amides can be synthesized by lipase mediated condensation of carboxylic acids and amines if an excess of either reactant is avoided. Chiral carboxylic esters have been resolved by lipase-catalyzed aminolysis. In the majority of these resolutions, Candida antarctica lipase B has been employed as the catalyst. A range of chiral amines has been resolved by lipase mediated acylation, using mainly the lipases from C. antarctica (B type) and Pseudomonas species. The enantiorecognition was frequently found to depend critically on the acylating agent and the reaction medium. Received December 20, 1999. Accepted January 1, 2000     

Ground-state multiplicities of atoms and positive ions

A procedure is developed to establish the ground-state multiplicities for atoms with any number of electrons. The procedure is applied to two- and three-electron systems. The results are that all neutral and positive two- and three-electron atoms have singlet (S=0) and doublet (S=1/2) ground states, respectively. Received: 10 August 1999 / Accepted: 6 October 1999 / Published online: 15 December 1999     

Epothilone B and its Derivatives as Novel Antitumor Drugs: Total and Partial Synthesis and Biological Evaluation

Summary.  Microtubule stabilizing natural products, as exemplified by paclitaxel (taxol^?), are being considered as novel drugs against malignant therapy resistent solid tumors. Among these compounds, epothilone B and some of its derivatives have emerged as particularly promising candidates for industrial development. The total and partial syntheses of these compounds are described in detail, and some of the most important recent results on their biological activity are discussed. Received December 3, 1999. Accepted December 6, 1999     

Chemoenzymatic Transformationsin Nucleoside Chemistry

Summary.  The synthetic potential of enzymes in connection with nucleoside analogue preparations is described. Received December 20, 1999. Accepted January 7, 2000     

Kinetic and Mechanistic Study of the Oxidative Deamination and Decarboxylation of L-Valine by Alkaline Permanganate

Summary.  The kinetics of the oxidation of L-valine, (L-Val) by permanganate in aqueous alkaline medium at a constant ionic strength of 0.50 molċdm⁻³ was studied spectrophotometrically. The reaction is of first order in [permanganate ion] and of fractional order in both [L-Val] and [alkali]. Addition of products has no significant effect on the reaction rate. However, increasing ionic strength and decreasing dielectric constant of the medium increase the rate. The oxidation process in alkaline medium has been shown to proceed via two paths, one involving the interaction of L-valine with permanganate ion in a slow step to yield the products, and the other path the interaction of alkali with permanganate ion to give manganate. Some reaction constants involved in the mechanism were determined; calculated and observed rate constants agree excellently. The activation parameters were computed with respect to the slow step of the mechanism. Received December 30, 1999. Accepted (revised) March 6, 2000     

MRINDO/S-CI calculation of the electronic spectra of azines

An MRINDO/S calculation completed by singly excited configuration interaction was performed on the azines vic-triazine, as-triazine, vic-tetrazine, and as-tetrazine. The importance of outer (Rydberg) atomic orbitals is stressed and it is found that a few transitions of these azines lead to an excited state with considerable Rydberg character. Ionization potentials of the azines are also interpreted. Received: 23 June 1998 / Accepted: 27 July 1999 / Published online: 15 December 1999     

Synthesis of carboranyl derivatives of deuteroporphyrin IX

Carboranylporphyrins, which can be used in boron neutron-choture therapy of cancer, were prepared from natural deuteroporphyrin IX, 3-amino-o-carborate, and 9-hydroxymethyl-m-carborane. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2337–2339 December, 1999.     

Synthesis of Optically Active α-Methyl β-Hydroperoxy Esters by Diastereoselective Singlet Oxygen Ene Reaction and Horseradish Peroxidase Catalyzed Kinetic Resolution

Summary.  Optically active diastereomeric β-hydroperoxy esters 4 have been prepared by singlet oxygen ene reaction of β,γ-unsaturated esters 3 and subsequent horseradish peroxidase (HRP) catalyzed kinetic resolution of the ene product. The highest enantiomeric excess (up to 95%) has been obtained for the isopropyl ester threo-4c, which establishes that the size of the remote ester functionality exercises appreciable control in the enantioselectivity of the enzymatic kinetic resolution. Received December 20, 1999. Accepted (revised) February 11, 2000