Group-theoretical Foundations for the Concept of Mandalas as Diagrammatical Expressions for Characterizing Symmetries of Stereoisomers

Group-theoretical foundations for the concept of mandalas have been formulated algebraically and diagrammatically in order to reinforce the spread of the unit-subduced-cycle-index (USCI) approach (S. Fujita, Symmetry and Combinatorial Enumeration in Chemistry, Springer-Verlag, Berlin-Heidelberg, 1991). Thus, after the introducton of right coset representations (RCR) (H\)G and left coset representations (LCR) G(/H) for the group G and its subgroup H, a regular body of G-symmetry is defined as a diagrammatical expression for a right regular representation (C ₁\)G, which is an extreme case of RCRs. The |G| substitution positions of the regular body as a reference are numbered in accord with the numbering of the elements of G and segmented into |G|/|H| of H-segments, which are governed by the RCR (H\)G. By regarding each H-segment as a substitution position, the H-segmented regular body is reduced into a reduced regular body, which can be regarded as a secondary skeleton for generating a molecule. The reference regular body (or H-segmented one) is operated by every symmetry operations of G to generate regular bodies (or H-segmented ones), which are placed on the vertices of a hypothetical regular body of G-symmetry. The resulting diagram (a nested regular body) is called a mandala (or a reduced mandala), which is a diagrammatical expression for specifying the G-symmetry of a molecule. The effect of a K-subduction on the regular bodies of a mandala (or a reduced mandala) results in the K-assemblage of the mandala (or the reduced mandala), where the resulting K-assemblies governed by the LCR G(/K) construct a |G|/|K|-membered orbit, which corresponds to a molecule of K-symmetry. The sphericity of the RCR (or the LCR) is used to characterize symmetrical properties of substitution positions and those of stereoisomers. The fixed-point vector for each mandala (or reduced mandala) in terms of row view and the number of fixed points of K-assembled mandalas (or K-assembled reduced mandalas) in terms of column view are compared to accomplish combinatorial enumeration of stereoisomers. The relationship between a mandala and a reordered multiplication table is discussed.     

Fluorinated styrene-based monomers for cyclopolymerizations

The synthesis of versatile fluorine compounds and monomers for conducting polymer research and cyclopolymerizations is presented. Semiprotected 2,3,5,6-tetrafluoroterephthaldehyde 1 could be elaborated through Wittig olefination chemistry, deprotection and reduction to the previously unknown 4-vinyl-2,3,5,6-tetrafluorobenzylalcohol 8 in good yields. Compound 8 can be reacted to form the malonate ester, and then alkylation on the malonate moiety in mild conditions affords difunctional monomer 3. Through sequential esterifications on the malonate moiety, and subsequent alkylation, compound 4, a difunctional monomer for cyclopolymerization bearing one styrene and one perfluoroaryl styrene moiety, has been obtained. Preliminary experiments show that it is possible to cyclopolymerize 4 under free radical conditions.     

Reagents for directed modification of biopolymers

The synthesis of new heterobifunctional reagents that are photo-activated, namely, 6-azido-1,3,4,5,7,8-hexafluoro-2-naphthoic acid (2), succinimido-6-azido-1,3,4,5,7,8-hexafluoro-2-naphthoate (3), andN-(n-butyl)-1,3,4,5,7,8-hexafluoro-2-naphthamide (4), which simulates the product of addition of acid2 to biopolymers, is described. The photolysis of azides2 and4 in methanol and pyridine was studied. Azide4 is superior to photoreagents based on perfluoroaromatic azides of the benzene series in spectral photosensitivity and rate of photolysis in the UV region (334–405 nm). When azide4 is irradiated with light at wavelengths above 400 nm, the rate of its photolysis in methanol increasesca. 10-fold in the presence of a singlet sensitizer, 9-aminoacridine, which makes reagent3 promising for designing binary systems sensitive to visible light. For Part 8, see Ref. 1. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 328–333, February, 1998.     

A Simple Method for Producing Pure (+) trans-1,2-Epoxylimonene

In this paper we report a simple methodology for obtaining (+) trans - 1,2 - epoxylimonene (1b) in high purity (>99% HRGC) and reasonable quantity. The mixture of 1a and 1b in CH₂Cl₂ is stirred with 1M NaHSO₃ in water. Under these conditions 1a is completely destroyed, while 1b is only partially destroyed.     

Recycling of undesired isomers of key intermediate for aprepitant

Abstract

A protocol for regeneration of key intermediate of aprepitant from its undesired diastereomers is described. This work features the recycling of at least one-third of the undesired isomers (ent-6, 7 and ent-7) to desired isomer 4 as the key early intermediate for the synthesis of aprepitant 1. The key step in our strategy involves diastereomeric salt preparation.     

An Improved Method for the Preparation OF 3,5-Difluorosalicylaldehyde and 3,5-Difluorosalicylic Acid #

An improved method for the synthesis of 3,5-difluorosalicylic acid (3b) and 3,5-difluorosalicylaldehyde (3a) is described. 2,4-Difluorophenol (4) undergoes a formylation reaction to afford aldehyde 3a which is oxidized to the desired acid 3b. This method avoids the use of the highly corrosive HF and fluorine gas and requires no special laboratory apparatus.

     

Facile Novel Synthesis and Reactions of Thiazolidin-4-one Derivatives for Antimicrobial Agents

A facile and fast procedure for synthesis of 3-phenyl-cyclohexane(1′-2)thiazolidin-4-one (1), which underwent condensation with glucose and p-chlorobenzaldehyde to afford 2 and 3, respectively. Compound 3 was used as precursor for the preparation of some fused heterocyclic compounds 4–7. Compound 4 was alkylated using dichloroacetone and chloroacetic acid to afford 8 and 9, respectively. Also, it reacted with acrylonitrile and hydrazine hydrate to afford 10 and 11, respectively. Compound 9 was condensed with p-chlorobenzaldehyde and glucose to afford 12 and 13, respectively. Selected members of the synthesized compounds were screened for antimicrobial activity.     

Pericyclic and Heteroelectrocyclic Mechanisms for the Cyclization of 1,3,5-Hexatrien-1-one and Its 6-Aza Analog

The cyclization of 1,3,5-hexatrien-1-one, 1, and the Z- and E-isomers of 1-aza-1,3-butadienylketene 3 were studied using the semiempirical AM1 and PM3 methods. Cyclizations of compounds 1 and Z-3 are shown to occur via a mono-rotation mechanism with barriers of 15.49 and 32.85 kcal/mol respectively. The reactions proceed via non-planar transition states which result from rotation of the methylene group for compound 1 and the imino group for compound Z-3. Cyclization of E-3 proceeds via a non-rotatory mechanism through a planar transition state. The activation barrier is 4.83 kcal/mol (AM1). The electronic structures of the initial and final states, and of some intermediate structures, including the transition states for the cyclization of compounds 1 and 3, were analyzed by the natural orbital method using HF/6-31G*//AM1 calculations. Energetic, structural, and orbital criteria indicate the heteroelectric mechanism for the cyclization of compound E-3 and the pericyclic mechanism for the cyclization of compounds 1 and Z-3.     

Test Films for the Determination of Aromatic Amines and Hydrazines in Aqueous Solutions

Conditions of the test determination of toxic aniline (I), N,N-dimethylaniline (II), N,N-diethylaniline (III), 2,2,4-trimethyl-1,2-dihydroquinoline (IV), 1,1-dimethylhydrazine (V), and phenylhydrazine (VI) as their 4,6-dinitrobenzofuroxan (I) and 5,7-dinitrobenzofurazan (II, III, IV, V, VI) derivatives in aqueous solutions were found. Visual and spectrophotometric measurement of the signal was used. The reagents were immobilized in nitrocellulose films. Optimal results of visual determination of color development in test films were obtained with reagents immobilized in nitrocellulose at their concentration of 5 mass % and pH of the test solution in the range 6.0–7.5. The spectrophotometric measurement of the signal of test films was performed at wavelengths of 500–560 nm for I, V, and VI and 610–620 nm for II, III, and IV. The detection limit for spectrophotometric measurement was 0.01, 0.18, 0.13, 0.15, 0.16, and 0.04 mg/L for I, II, III, IV, V, and VI, respectively. The analytical range of the toxicants was 0.05–6.0 mg/L. Test determination is possible in the presence of alkylamines, ammonia, phenols, carboxylic acids, and inorganic salts.     

Deuterated Disaccharides for the Investigation of Protein-Carbohydrate Interactions-Application of Bioaffinity-and STD-NMR

ABSTRACT

NMR spectroscopic analysis of carbohydrates often suffers from severe overlap of resonance signals, especially in ¹H NMR spectra. Therefore, we synthesized four 2,3,4-trideuterio-α-L-fucose containing disaccharides, α-L-Fuc-(1→6)-β-D-GlcNAc-OMe 1, α-L-Fuc-(1→4)-β-D-GlcNAc-OMe 2, α-L-Fuc-(1→3)-β-D-GlcNAc-OMe 3, and α-L-Fuc-(1→2)-β-D-Gal-OMe 4. Compounds 1 to 4 are well suited to be subjected to NMR conformational analysis because their ¹H NMR spectra show almost no overlap of signals. The deuterated disaccharides 1 to 4 will therefore be used as NMR probes for the exploration of fucose-binding proteins. With a mixture of the corresponding non-deuterated disaccharides it is demonstrated that recently developed parallel NMR screening protocols, Bio-Affinity NMR and STD-NMR, deliver fast and robust tools to assay the compounds synthesized for protein-binding affinity.     

A green synthetic process for the preparation of water-soluble drugs: pegylation of menadiol and podophyllotoxin

Abstract

Pegylation of drugs is a frequently employed strategy used to improve the pharmacokinetics and pharmacodynamics of drugs. Despite this, the virtues of pegylation as a green synthetic approach to enhance the water solubility of drugs has not been discussed. Using two well-known active pharmaceutical ingredients, menadiol sodium diphosphate (1) and the semisynthetic natural product, etoposide phosphate (3), green metrics for the processes of pegylation versus phosphorylation are presented and discussed. Menadiol (2) was prepared by an ultrasound mediated reduction of menadione (9). In a study done by the National Cancer Institute, PEG podophyllotoxin 12 was screened for activity against 60 different human cancer cell lines and the desired anticancer properties of podophyllotoxin (5) were retained. As podophyllotoxin (5) is a natural product, the concept of “green drugs” is espoused.     

Preparation of Some Fused Pyridopyrimidine and Pyridothienotriazine Derivatives for Biological Evaluation

Compounds 2 and 9 were formed using 3-(4-chloro-phenyl)-1-pyridin-2-yl propenone ( 1 ) and malononitrile or ethyl cyanoacetate, respectively. The pyridine derivative 2 was in turn used as a precursor for the preparation of some pyridopyrimidine and fused pyridopyrimidine derivatives 3–8 On the other hand, the pyridine derivative 9 was used for the preparation of thienopyridine derivatives 11 and 12 Nitrozation of compound 12 afforded pyridothienotriazine derivative 13 Some of the prepared products showed potent antimicrobial activity.     

New Tetrafunctionalized Cone Calix[4]arenes as Neutral Hosts for Anion Recognition

Abstract

The synthesis and anion binding properties of several new cone calix[4]arenes having different flexibility and tetrafunctionalized at the upper rim with various type of hydrogen bonding donor groups such as thioureas (1–3), trifluoroacetamides (4, 5) and perfluorinated alcohols (6) are reported. The results obtained show that thiourea receptors are the most effective in the complexation of all anions and that the rigid cone compound 2 is more efficient than the mobile cone analog 1 in the binding of spherical anions, whereas the reverse is true for the complexation of tetrahedral H₂PO₄ ^? anion.     

Experimental evidence for the breakdown of conventional elasticity in smectics A

Abstract

Grinstein and Pelcovits have shown that anharmonic terms in the ‘microscopic’ elastic free energy lead to a qualitative change in the macroscopic elastic expressions describing the equilibrium behaviour of smectic A liquid crystals. In particular, they showed that the elastic moduli B(ω = 0,q) and K ₁ (ω = 0,q) vanish and diverge, respectively as In(q) for small wavevector q. In the dynamical case (ω ≠ 0), as predicted by Mazenko, Ramaswamy and Toner, the influence of anharmonicity is more dramatic: some viscosities diverge as 1/ω We present in this paper a finite ω version of the non-linear hydrodynamics of smectic A and what we believe to be the first experimental evidence of the decrease of the layer compressional modulus B(ω, q), at low frequency ω and wavevector q.     

A criterion for the confluence of two seams of conical intersection in triatomic molecules

It is shown that the cross product t ^{I J} (R _x )≡g ^{I J} (R _x )×h ^{I J} (R _x ), where g _τ ^{I J} (R)=(c ^I (R _x )−c ^J (c ^I (R _x )+c ^J (R _x )), h _τ ^{I J} (R)=c ^I (R _x )^† c ^J (R _x ), τ is an internal nuclear coordinate, the c ^I (R) satisfy [H(R)−E _I (R)]c ^I (R)=0 and H(R) is the electronic Hamiltonian matrix, is a unique property of a conical intersection at R _x . t ^{I J} (R _x )=0 when R _x is located at the intersection of two (or more) seams of conical intersection. This criterion for an intersection of two seams of conical intersection has important implications for algorithms that seek to locate such points. Here it␣is␣used to analyze the trifurcation of a generic C_2v ^2S+1 A−^2S+1 B seam of conical intersection, analogous to those recently found in AlH₂ and CH₂. Received: 31 July 1997 / Accepted: 27 August 1997     

A Versatile Approach for Synthesis of 2,3-Dimethyl Chroman-4-ones,Intermediate for Calanolide Anti-HIV Agents,VIA Aldol/Mitsunobu Reactions

Combined aldol/Mitsunobu reactions have been employed for the first time for synthesis of 2,3-dimethyl chroman-4-ones, intermediates for calanolide anti-HIV agents. Thus, the lithium enolate of chromene 1 reacted with acetaldehyde at -78°C to afford the aldol products 4 and 5. Under Mitsunobu conditions (Ph₃P/DEAD), the syn aldol product 4 led to the formation of trans-2,3-dimethyl chroman-4-one 2 while the anti aldol product 5 yielded both trans and cis derivatives (2 and 3). The use of other phosphorous and azo compounds in this reaction has also been investigated.     

A new strategy for isoflavone C-glycoside synthesis: The total synthesis of puerarin

Abstract

Given that C-glucosylisoflavones often possess promising biological activities, the development of an efficient synthetic method for this type of molecules is useful for drug discovery. Accordingly, a highly efficient five-step strategy was developed for the total synthesis of puerarin, an isoflavone C-glycoside. An alkyl substituent 4-CH₃OC₆H₄CH₂CH₂ with an electron-donating group on the aromatic ring was used to enhance the reactivity of phenol and the regioselectivity of O-C rearrangement of phenol glycoside. Thus, coupling of the ethylbenzene derivative of a phenol 1c with glycosyl trifluoroacetimidate 2 resulted in C-glycoside 3c in a 46.2% yield, which was easily de-tert-butylated with trifluoroacetic acid and oxidized with 2,3-dicyano-5,6-dichlorobenzoquinone to produce deoxybenzoin 5. The ring closure reaction of 5 followed by deprotection gave puerarin. This new synthetic strategy is also suitable for the total synthesis of other C-glucosylisoflavones.     

Improved Methods for the Synthesis of Irbesartan,an Antihypertensive Active Pharmaceutical Ingredient

New methods for the preparation of irbesartan 1 have been described. The dehydration and tetrazole formation in one step from substituted cyclopentane derivative 7 with tributyltin chloride and sodium azide is described. Selective hydrolysis of nitrile 3 with HCl has also been described in the preparation of N‐acylaminocyclopentane‐2‐carboxylic acid 4, which is the key intermediate for the preparation of irbesartan. The impurity profiling of irbesartan has also been discussed.     

A General Method for the Synthesis of N,N-Dialkylaminobutylamines

A general method for the synthesis of N,N-dialkylaminobutylamines 4 from readily available chloroacetamides 6 is described.     

Stability Indicating Hplc Method for the Determination of Sparfloxacin (Spar)

ABSTRACT

A rapid, sensitive and stability indicating method for the determination of sparfloxacin (SPAR) by RP - HPLC has been developed on a Merck RP - Select B (5 μm; 12.5 cm x 4.0 mm) column using a mobile phase of water: acetonitrile: triethylamine (80 : 20 : 0.2 v/v) pH of which was adjusted to 2.6 with orthrophosphoric acid. The flow rate was 1 ml / min. and the detection was carried out at 304 nm using Waters 486 variable wavelength detector. The retention time for SPAR was 7.2 min. Linearity range was from 8 - 1000 ppm. The method showed good precision and accuracy when applied to two brands of tablets containing SPAR. In alkaline media SPAR is stable where as it undergoes degradation in acidic and oxidising conditions generating different degradation products the nature of which is required to be established. The proposed method nicely separates the degraded products from SPAR and hence can be used as stability indicating method for the assay of SPAR.