Synthesis and Juvenile Hormone Activity of Some Terpenoid Phenyl Ethers

Thirty eight new compounds with juvenile hormone (JH) activity were synthesized and evaluated biologically on Bombyx mori L. Among them, the activities of 7,8-epoxy-4,8-dimethyl-1 -(p-ethylphenoxy)-3-undecene and 7,8-epoxy-4,8-dimethyl-l-(p-methylphenoxy)-3-undencene were proved to be more than two thousand times as high as that of the C₁₈-Cecropia JH (mixed isomers). Structure-activity relationship of these compounds was discussed.     

Synthesis and Biological Activity of Analogs of the Cecropia Juvenile Hormone with Different Alkyl Substituents at C-7 and C-11

Sixteen new Cecropia juvenile hormone (JH) analogs with different alkyl substituents at C–7 and C–11 were synthesized as stereoisomeric mixtures. The epoxides with n-propyl or n-butyl and methyl groups at C-11 and methyl or ethyl group at C-7 showed high JH activity on Bombyx mori L. Structure-activity relationship of the JH analogs was discussed.     

A Synthesis of dl-C17-Cecropia Juvenile Hormone

A novel synthesis of dl-C₁₇-Cecropia juvenile hormone (I) was accomplished.     

Ribonucleic Acid Metabolism in Germinating Soybeans

A stereoselective synthesis of methyl trans, trans-farnesoate (I) from isoprenyl bromide and geraniol is described. dl-C₁₇-Cecropia juvenile hormone (IV) was synthesized from it in a stereoselective manner.     

Conversion of Farnesol into Methyl dl-12-Homo-10-trans-juvenate,the 10-trans-lsomer of dl-C17-Cecropia Juvenile Hormone

Methyl dl-12-homo-10-trans-juvenate (III) was synthesized from farnesol (IV) in eight steps involving stereoselective conversion of the trans-terminal methyl group to an ethyl group. The product (III) was less active than dl-C₁₇-Cecropia juvenile hormone on both Tenebrio molitor and Galleria mellonella.     

Inactivation of Bacteriophages by ε-Poly-l-lysine Produced by Streptomyces

Degradation of a β-O-4lignin substructure model dimer by a white rot fungus, Phanerochaete chrysosporium, was investigated using a culture containing H₂¹⁸O, and the following conclusions were made. a) The direct hydrolysis at C_β of the β-O-4 dimer was not involved in formation of arylglycerol. b) About half of the oxygen at the benzyl (C_α) position of the glycerol was derived from H₂O (H₂¹⁸O) and the other half was from the oxygen at the benzyl (C_α) position of the substrate β-O-4 dimer. c) But, the oxygen at the C_α position of the substrate β-O-4 dimer did not migrate to the C_α position of the aryglycerol.     

The effect of β‐methylation on the conformation of α, β‐dehydrophenylalanine: a DFT study

Dehydroamino acids are non‐coded amino acids that offer unique conformational properties. Dehydrophenylalanine (ΔPhe) is most commonly used to modify bioactive peptides to constrain the topography of the phenyl ring in the side chain, which commonly serves as a pharmacophore. The Ramachandran maps (in the gas phase and in CHCl₃ mimicking environments) of ΔPhe analogues with methyl groups at the β position of the side chain as well as at the C‐terminal amide were calculated using the B3LYP/6‐31 + G** method. Unexpectedly, β‐methylation alone results in an increase of conformational freedom of the affected ΔPhe residue. However, further modification by introducing an additional methyl group at C‐terminal methyl amide results in a steric crowding that fixes the torsion angle ψ of all conformers to the value 123°, regardless of the Z or E position of the phenyl ring. The number of conformers is reduced and the accessible conformational space of the residues is very limited. In particular, (Z)‐Δ(βMe)Phe with the tertiary C‐terminal amide can be classified as the amino acid derivative that has a single conformational state as it seems to adopt only the β conformation. Copyright © 2009 European Peptide Society and John Wiley & Sons, Ltd.     

Synthesis of New Analogues of the Cecropia Juvenile Hormone with a Cyclopentane or Cyclohexane Ring at the Terminal Position

Two new juvenile hormone analogues with a cyclopentane (IVa) or cyclohexane (IVb) rings at the terminal position were prepared and were shown to possess high juvenile hormone activity.     

Effects of a synthetic juvenile hormone and some analogues on Ephestia spp. (Lepidoptera: Phycitidae)

Depending on their stage of development, treatment of mature larvae of Ephestia kühniella with a synthetic juvenile hormone resulted in the production of super larvae (which invariably prolonged larval life) and larval-pupal intermediates. When migrating last-instar larvae were treated with the juvenile hormone analogues (JHA) ethyl-3,7, n-trimethyldodeca-2,4-dienoate (ZR512) and isopropyl ii-methoxy-3,7, ii-trimethyldodeca-2,4-dienoate (ZR515), larval-pupal intermediates and pupal mortality were induced. However, when applied topically, ZR515 appeared more effective than ZR512. Both analogues prevented adult emergence when topically applied to the migrating larvae at doses between 28–52 ng. One-day-old pupae were most susceptible while older individuals became less sensitive with age. When larvae pupated in corrugated cardboard rolls were treated with ZR512 those of both E. cautella and E. kiihniella failed to emerge. At an estimated dose of 179 ng cm^-2, ZR515 prevented 77^-6%E. cautella and 100%E. kühniella larvae from emerging as adults. The control of Ephestia by JHA treatment of the pupation sites is discussed.     

Juvenile hormone synthesis by ring glands of the blowfly Lucilia cuprina

The major radiolabelled product released from ring gland and brain-ring gland complexes of third instar larval and pre-pupal stages of the sheep blowfly Lucilia cuprina upon incubation with L-[methyl-³H]methionine corresponded to one diastereomer of juvenile hormone III bisepoxide (JHB₃). Endocrine glands incubated with the juvenile hormone precursor 2E,6E-farnesoic acid released increased quantities of JHB₃, together with significant amounts of juvenile hormone III but not the isomeric methyl 2E-6,7-epoxyfarnesoate. Synthesis of JHB₃ was developmentally and neurally regulated. Ring glands and brain-ring gland complexes from third instar larvae released more JHB₃ than comparable preparations from pre-pupae, while isolated corpus allatum segments of the gland were more active than intact brain-gland complexes. These results reinforce the emerging status of JHB₃ as the characteristic juvenile hormone of dipteran insects. Arch. Insect Biochem. Physiol. 34:239–253, 1997. © 1997 Wiley-Liss, Inc.     

Growth Promotion in Pea Stem Sections. III. By Alkyl Nitriles, Alkyl Acetylenes and Insect Juvenile Hormones

C₁₄, C₁₅, and C₁₆ alkyl nitriles, and C₁₆ and C₁₈ alkyl acetylenes at 10 to 105 micromolar concentrations promote the growth of stem sections from red-light-exposed seedlings of dwarf peas (Pisum sativum L. cv. Progress No. 9). Similar results were obtained with substances active as insect juvenile hormones, namely farnesol, the racemic ethyl ester of 1 of the natural hormones, and a “synthetic juvenile hormone” mixture, the latter 2 having as high an activity in the pea assay as any lipid reported previously. A sterically nearly identical compound, methyl-RS-10,11-epoxyfarnesoate, is a weak insect hormone and did not promote plant growth. Thus activity in peas and in insects is in some cases parallel. Other similarities and some differences are discussed. Peas appear to require molecules longer than 20A, while insect activity is maximal at that length. All active molecules are ineffective in promoting pea stem elongation by themselves, indole acetic acid must also be present. The lipid effect in plants and the juvenile hormone response in insects have much in common and the evidence suggests they could have a similar locus of action in a membrane controlling respiratory function.     

Multiple classification performance of juvenile chimpanzees,normal children,and retarded children

The cognitive capacities of juvenile chimpanzees, normal children, and retarded children were evaluated by using a nonverbal, Piagetian-type multiple classification task. The three groups of subjects were tested with the same two by two stimulus matrix, which was formed by combining two different colors with two different shapes. On each problem the subjects were required to select one of four stimulus items from the response tray and place it inside the empty cell of the stimulus matrix. It was found that the human and nonhuman primates tested were able to select objects with correct color and shape cues (C⁺/S⁺)significantly more often than the other objects with only color cues correct (C⁺/S^-), only shape cues correct (C^-/S⁺), or neither cue correct (C^-/S^-). Although the two groups of human children were able to select the C⁺/S⁺ objects about 100% of the time by the end of testing, the normal children required significantly fewer problems than the retarded children. The juvenile chimpanzees needed significantly more problems than the human subjects before they consistently selected the C⁺/S⁺ object on the first trial and attained a level of correct responding that was above chance. Moreover, their level of performance did not exceed 70% correct. These data suggest that the human children (both normal and retarded) used a conceptual strategy, while the juvenile chimpanzees employed a perceptual strategy to solve the multiple classification problems. The relationship between language and conceptual problem-solving strategies for Piagetiantype tasks is discussed. Portions of the data reported in this study were presented at the Annual Meeting of the Southern Psychological Association, Atlanta, Georgia, March 15–18, 1978.     

Chemical synthesis of the 17-propanamide derivatives of stereoisomeric Δ14-17α- and 17β-estradiols: potential 17β-hydroxysteroid dehydrogenase inhibitors

The 17-propanamide derivatives of diastereomeric Δ¹⁴-17α- and 17β-estradiols, the potential candidates of a 17β-hydroxysteroid dehydrogenase (17β-HSD) inhibitor, were synthesized in 11 steps from estrone. The principal reactions employed involved in (1) conversion of estrone to the corresponding Δ¹⁴-estrone, (2) Grignard reaction of Δ¹⁴-estrone with allylmagnesium bromide followed by regioselective hydroboration of the resulting stereoisomeric 17ξ-allyl-Δ¹⁴-17ξ-ols with 9-borabicyclo[3.3.1]nonane (9-BBN), and (3) direct amidation of the 17ξ-O-/17ξ-C-spiro-γ-lactones with NH₃ under positive pressure of H₂.     

Glutamate synthase (NADH) from lupin nodules. Specificity of the 2-oxoglutarate site

The binding of substrate analogues including potential alternative substrates, to glutamate synthase (NADH) (l-glutamate: NAD⁺ oxidoreductase (transaminating) E.C. 1.4.1.14) has been investigated by studying competitive inhibition with respect to 2-oxoglutarate. Binding requires two terminal carboxyl groups on a C₅ straight chain molecule although some C₄ molecules bind weakly. Bulky substituents at C₂ decrease or prevent binding. Glutarate, the most potent inhibitor, binds much less tightly than the substrate. A 2-oxo group in a molecule other than the substrate does not appear to contribute significantly to binding. None of the analogues was able to act as an alternative substrate.     

Charge inversion at position 68 of the glucagon and glucagon‐like peptide‐1 receptors supports selectivity in hormone action

Glucagon and glucagon‐like peptide‐1 (GLP‐1)are two structurally related hormones that acutely regulate glucose control in opposite directions through homologous receptors. The molecular basis for selectivity between these two hormones and their receptors is of physiological and medicinal importance. The application of co‐agonists to enhance body weight reduction and correct multiple abnormalities associated with the metabolic syndrome has recently been reported. Substitution of amino acids 16, 18, and 20 in glucagon with those found in GLP‐1 and exendin‐4 were identified as partial contributors to balanced, high potency receptor action. The amidation of the C‐terminus was an additional glucagon‐based structural change observed to be of seminal importance to discriminate recognition by both receptors. In this work, the molecular basis for receptor selectivity associated with differences in C‐terminal peptide sequence has been determined. A single charge inversion in glucagon and GLP‐1 receptor sequence at position 68* was determined to significantly alter hormone action. Changing E68* in GLP‐1R to the corresponding Lys of GCGR reduced receptor activity for natural GLP‐1 hormones by eightfold. The enhanced C‐terminal positive charges in GLP‐1 peptides favor the native receptor's negative charge at position 68*, while the unfavorable interaction with the C‐terminal acid of native glucagon is minimized by amidation. The extension of these observations to other glucagon‐related hormones such as oxyntomodulin and exendin, as well as other related receptors such as GIPR, should assist in the assembly of additional hormones with broadened pharmacology. Copyright © 2010 European Peptide Society and John Wiley & Sons, Ltd.     

Synthesis of new 4-(E)-alkenylpyrrolo[1,2-a]quinoxalines as antileishmanial agents by Suzuki-Miyaura cross-coupling reactions

A series of new 4-(E)-alkenylpyrrolo[1,2-a]quinoxaline derivatives, structural analogues of alkaloid chimanine B, was synthesized in good yields using efficient palladium(0)-catalyzed Suzuki-Miyaura cross-coupling reactions. These new compounds were tested for in vitro antiparasitic activity upon Leishmania amazonensis and Leishmania infantum strains. Biological results showed activity against the promastigote forms of L. amazonensis and L. infantum with IC₅₀ ranging from 0.5 to 7 μM. From a Structure-Activity Relationships point of view, these pharmacological results mainly enlightened the importance of the 4-lateral C₆, C₇ or C₈ α-unsaturated trans-alkenyl chain of unsubstituted pyrrolo[1,2-a]quinoxaline moiety.     

Synthesis of (±)-8,16,26,34-Tetrahydroxy-6,10,14,18,24,28,32,36-octaoxohentetracontane as a Potent Synthetic Analog of Race T Toxin Produced by Helminthosporium maydis

A stereoisomeric mixture of (±)-8,16,26,34-tetrahydroxy-6,10,14,18,24,28,32,36-octaoxo-hentetracontane (C₄₁) was synthesized together with (±)-8,16-dihydroxy-6,10,14,18-tetraoxotri-cosane (C₂₃), utilizing bis addition of pentyl-l,5-dimagnesiumbromide to two moles of a C₁₈-alde-hyde.     

Activite de l'hormone juvenile en C17 (JH-II) chez Locusta migratoria

The effects of C₁₇ juvenile hormone (JH-II) have been investigated in Locusta on morphogenesis, ovarial development, and pigmentation, by means of injections in oil. These effects have been compared with those of injecting C₁₈ juvenile hormone (JH-I) and of implanting corpora allata into Locusta. JH-I and JH-II are similar in their effects upon morphogenesis and pigmentation, and also on ovarial development in which JH-III has been found to be more effective in other insects. Injections of JH-I and JH-II have similar effects to those seen after implanting corpora allata. However in experiments on heart beat (in which the corpora allata have been shown to be involved) JH-I is the only substance to increase the rate of heart beat in the same way as active corpora allata. These observations are discussed, and it is concluded that JH-I is the hormone with effects nearest to those of the corpus allatum hormone itself.     

PREPARATION OF 3′-C-BRANCHED URIDINE ANALOGUES,SUITABLE FOR CONVERSION INTO FUNCTIONALISED 3′-C-METHYLENE DERIVATIVES

A novel method for preparation of 1-[2-O-(tert-butyldimethylsilyl)-3-deoxy-3-C-hydroxymethyl-5-O-monomethoxytrityl-β-D-ribo-pentofuranosyl]uracil by hydroboration of corresponding 3′-deoxy-3′-C-methyleneuridine derivative has been developed. Further conversion of the hydroxyl function into different leaving groups was carried out to afford derivatives suitable for conversion into various 3′-C-branched uridine analogues through substitution.