The Experts below are selected from a list of 249 Experts worldwide ranked by ideXlab platform
Robert M. Williams - One of the best experts on this subject based on the ideXlab platform.
-
Molecular Basis for Spirocycle Formation in the Paraherquamide Biosynthetic Pathway
2019Co-Authors: Amy E. Fraley, Robert M. Williams, Kersti Caddell Haatveit, Samantha P. Kelly, Sean A. Newmister, Janet L. Smith, K. N. Houk, David H. ShermanAbstract:<div> <div> <div> <p>The Paraherquamides are potent anthelmintic natural products with complex heptacyclic scaffolds. One key feature of these molecules is the spiro-oxindole moiety that lends a strained three-dimensional architecture to these structures. The flavin monooxygenase PhqK was found to catalyze spirocycle formation through two parallel pathways in the biosynthesis of Paraherquamides A and G. Two new Paraherquamides (K and L) were isolated from a ΔphqK strain of Penicillium simplicissimum, and subsequent enzymatic reactions with these compounds generated two additional metabolites Paraherquamides M and N. Crystal structures of PhqK in complex with various substrates provided a foundation for mechanistic analyses and computational studies. While it is evident that PhqK can react with various substrates, reaction kinetics and molecular dynamics simulations indicated that the dioxepin-containing Paraherquamide L was the favored substrate. Through this effort, we have elucidated a key step in the biosynthesis of the Paraherquamides, and provided a rationale for the selective spirocyclization of these powerful anthelmintic agents. </p></div></div><div><div> </div> </div> </div>
-
comparative analysis of the biosynthetic systems for fungal bicyclo 2 2 2 diazaoctane indole alkaloids the notoamide Paraherquamide and malbrancheamide pathways
MedChemComm, 2012Co-Authors: Krithika Srinivasan, Robert M. Williams, Timothy J. Mcafoos, James D. Sunderhaus, Jennifer M. Finefield, Sachiko Tsukamoto, Hong Tran, David H. ShermanAbstract:The biosynthesis of fungal bicyclo[2.2.2]diazaoctane indole alkaloids with a wide spectrum of biological activities have attracted increasing interest. Until recently, the details of these biosynthetic pathways have remained largely unknown due to lack of information on the fungal derived biosynthetic gene clusters. Herein, we report identification of three new fungal gene clusters responsible for biosynthesis of a select group of bicyclo[2.2.2]diazaoctane indole alkaloids including (+)-notoamide, Paraherquamide and malbrancheamide by genome mining. In each gene cluster, we identified a non-ribosomal peptide synthetase, a variant number of prenyltransferases, and a series of oxidases responsible for the diverse tailoring modifications of the cyclodipeptide structural core. Based on the comparative analysis of four natural product metabolic systems including (+)/(−)-notoamide, Paraherquamide and malbrancheamide, we were able to propose an enzyme for each step in the respective biosynthetic pathways through deep gene annotation and on-going biochemical studies. We proposed that two different types of intramolecular Diels-Alderases operate to generate the monooxopiperazine and dioxopiperazine ring systems for this class of alkaloid natural products.
-
Comparative analysis of the biosynthetic systems for fungal bicyclo[2.2.2]diazaoctane indole alkaloids: the (+)/(-)-notoamide, Paraherquamide and malbrancheamide pathways.
MedChemComm, 2012Co-Authors: Krithika Anand Srinivasan, Robert M. Williams, Timothy J. Mcafoos, James D. Sunderhaus, Hong T. Tran, Jennifer M. Finefield, Sachiko Tsukamoto, David H. ShermanAbstract:The biosynthesis of fungal bicyclo[2.2.2]diazaoctane indole alkaloids with a wide spectrum of biological activities have attracted increasing interest. Until recently, the details of these biosynthetic pathways have remained largely unknown due to lack of information on the fungal derived biosynthetic gene clusters. Herein, we report identification of three new fungal gene clusters responsible for biosynthesis of a select group of bicyclo[2.2.2]diazaoctane indole alkaloids including (+)-notoamide, Paraherquamide and malbrancheamide by genome mining. In each gene cluster, we identified a non-ribosomal peptide synthetase, a variant number of prenyltransferases, and a series of oxidases responsible for the diverse tailoring modifications of the cyclodipeptide structural core. Based on the comparative analysis of four natural product metabolic systems including (+)/(−)-notoamide, Paraherquamide and malbrancheamide, we were able to propose an enzyme for each step in the respective biosynthetic pathways through deep gene annotation and on-going biochemical studies. We proposed that two different types of intramolecular Diels-Alderases operate to generate the monooxopiperazine and dioxopiperazine ring systems for this class of alkaloid natural products.
-
Synthetic approaches to the bicyclo[2.2.2]diazaoctane ring system common to the Paraherquamides, stephacidins and related prenylated indole alkaloids
Chemical Society reviews, 2009Co-Authors: Kenneth A. Miller, Robert M. WilliamsAbstract:The bicyclo[2.2.2]diazaoctane ring system is common to a number of highly biologically active secondary metabolites isolated from numerous species of fungi. In this tutorial review, we describe the varied synthetic approaches that have been employed to construct this ring system in the course of recent total synthesis endeavors, and this review should be of interest to synthetic organic chemists and natural product chemists. Detailed herein are a number of synthetic disconnections including intramolecular SN2′ cyclizations, biomimetic Diels–Alder reactions, radical cyclizations, and cationic cascade reactions.
-
Studies on Paraherquamide biosynthesis: synthesis of deuterium-labeled 7-hydroxy-pre-Paraherquamide, a putative precursor of Paraherquamides A, E, and F
Tetrahedron, 2009Co-Authors: Konrad Sommer, Robert M. WilliamsAbstract:Abstract The stereocontrolled, asymmetric synthesis of triply deuterium-labeled 7-hydroxy-pre-Paraherquamide (27) was accomplished, employing a diastereoselective intramolecular SN2′ cyclization strategy. The deuterium-labeled substrate was interrogated in a precursor incorporation experiment in the Paraherquamide-producing organism Penicillium fellutanum. The isolated sample of Paraherquamide A revealed incorporation of one of the two geminal deuterons of the CD2-group at C-12 exclusively. The lack of signals for the second deuteron of the CD2-group at C-12 and for the CH2D-group (C-22/C-23) suggests that this substrate suffered an unexpectedly selective catabolic degradation and metabolic re-incorporation of deuterium thus casting doubt on the proposed biosynthetic intermediacy of 27. Consideration of alternative biosynthetic pathways, including oxidation of the indole C-6 position prior to hydroxylation at C-7 or oxidative spiro-contraction of pre-Paraherquamide prior to construction of the dioxepin is discussed. The synthesis of 27 also provides for a concise, asymmetric stereocontrolled synthesis of an advanced intermediate that will be potentially useful in the synthesis of Paraherquamides E and F.
Juan F. Sanz-cervera - One of the best experts on this subject based on the ideXlab platform.
-
Asymmetric Total Synthesis of (−)-VM55599: Establishment of the Absolute Stereochemistry and Biogenetic Implications
Journal of the American Chemical Society, 2002Co-Authors: Juan F. Sanz-cervera, Robert M. WilliamsAbstract:The first asymmetric biomimetic total synthesis of VM55599 (13) has been achieved utilizing an intramolecular Diels-Alder cycloaddition as a key step. The synthetic material was utilized to elucidate the absolute stereochemistry of the natural product. The results are discussed in terms of a unified biogenesis of the Paraherquamides and VM55599.
-
Studies on the biosynthesis of Paraherquamide. Construction of the amino acid framework
Tetrahedron, 2001Co-Authors: Emily M. Stocking, Juan F. Sanz-cervera, Clifford J. Unkefer, Robert M. WilliamsAbstract:Abstract It has been previously established in this laboratory that the β-methyl-β-hydroxyproline moiety of the potent anthelmintic agent Paraherquamide A, is biosynthetically derived from l -isoleucine. The downstream events from l -Ile to Paraherquamide A have now been investigated. The synthesis of [1- 13 C]-labeled l -β-methylproline is described by means of a Hoffman–Loeffler–Freytag reaction sequence from [1- 13 C]- l -Ile. This amino acid is shown to be a direct biosynthetic precursor to Paraherquamide A by feeding and incorporation experiments in growing cultures of Penicillium fellutanum . Three tryptophan-containing dipeptides of l -β-methylproline have been constructed: [ 13 C 2 ]-2-(1,1-dimethyl-2-propenyl)- l -tryptophanyl-3( S )-methyl- l -proline; [ 13 C 2 ]-3( S )-methyl- l -prolyl-2-(1,1-dimethyl-2-propenyl)- l -tryptophan and [ 13 C 2 ]- cyclo -2-(1,1-dimethyl-2-propenyl)- l -tryptophan-3( S )-methyl- l -proline. [α- 15 N, 1- 13 C]-2-(1,1-Dimethyl-2-propenyl)- l -tryptophan was also prepared but none of these substances were found to serve as biosynthetic precursors to Paraherquamide A.
-
Biosynthesis of Prenylated Alkaloids Derived from Tryptophan
Biosynthesis, 2000Co-Authors: Robert M. Williams, Emily M. Stocking, Juan F. Sanz-cerveraAbstract:The biosynthesis of prenylated indole alkaloids and related natural substances derived from tryptophan is reviewed. The families of compounds covered in this review include the brevianamides, austamides, Paraherquamides, marcfortine, roquefortine, aszonalenin, echinulin, verruculogen, the fumitremorgins, a-cyclopiazonic acid, and the ergot alkaloids. Although other families of naturally occurring prenylated indole alkaloids exist, such as the iridoids, this review is intended to examine the biosynthesis of the groups selected based on their structural and biogenetic similarities. In addition, the biosynthesis of the families selected for this chapter have not, to the best of our knowledge, been previously reviewed.
-
A Synthetic Model for the [4+2] Cycloaddition in the Biosynthesis of the Brevianamides, Paraherquamides, and Related Compounds
Tetrahedron, 2000Co-Authors: Juan F. Sanz-cerveraAbstract:Abstract The reactivity of model systems for the proposed [4+2] cycloaddition in the biosynthesis of the brevianamides, Paraherquamides, and marcfortines is explored. The model for the intermolecular reaction reveals that the cycloaddition takes place under mild conditions only if activated, very reactive dienophiles are used. When relatively unreactive dienophiles such as cyclopentene and cyclohexene are used, harsh reaction conditions and/or a Lewis acid catalyst are necessary for the reaction. In contrast, the model for the intramolecular reaction demonstrates that the cycloaddition takes place within a few hours at room temperature, even in the absence of a Lewis acid catalyst. Conclusions drawn from these results are discussed in relation to the biosynthesis of the aforementioned metabolites.
-
Reverse Prenyl Transferases Exhibit Poor Facial Discrimination in the Biosynthesis of Paraherquamide A, Brevianamide A, and Austamide
Journal of the American Chemical Society, 2000Co-Authors: Emily M. Stocking, Robert M. Williams, Juan F. Sanz-cerveraAbstract:The mode of attachment of dimethylallyl pyrophosphate (DMAPP) in the biosynthesis of the indole alkaloids Paraherquamide A, austamide, and brevianamide A has been studied. Feeding experiments on Penicillium fellutanum, Penicillium brevicompactum, and Aspergillus ustus using [13C2]-acetate showed isotopic scrambling of the geminal methyl groups originating from C-2 of the indole ring precursors in Paraherquamide A, brevianamide A, and austamide biosynthesis. The labeling patterns suggest that the methyl groups of dimethylallyl pyrophosphate become equivalent during the biosyntheses; a non-face-selective SN‘ mechanism has been invoked to account for these observations.
Alan P. Robertson - One of the best experts on this subject based on the ideXlab platform.
-
Effect of antagonists of the tribendimidine-concentration-contraction plots allowing the estimation of pA2 values.
2015Co-Authors: Alan P. Robertson, Sreekanth Puttachary, Samuel K. Buxton, Richard J MartinAbstract:A: Effect of derquantel pA2 = 6.42 ± 0.12 mean ± s.e. (n = 108). B: Effect of Paraherquamide pA2 = 7.21 ± 0.13 mean ± s.e. (n = 90). C: Effect of methyllycaconitine (MLA) pA2 = 6.61 ±0.09 mean ± s.e. (n = 90).
-
nAChR resolved at the single-channel level in Ascaris suum
2013Co-Authors: Hai Qian, Richard J Martin, Alan P. RobertsonAbstract:suum have demonstrated the presence of three (N-, L-, and B-) subtypes of cholinergic receptor mediating contraction of body wall muscle in parasitic nematodes (1). In the present study, these ionotropic acetylcholine (ACh) receptors (nAChRs) were activated by levamisole and bephenium under patch-clamp conditions and competitively antagonized by Paraherquamide and 2-desoxoParaherquamide. A number of recordings exhibited three separate current amplitude levels, indicating the presence of small, intermediate, and large conductance subtypes of receptor. The mean conductance of the small conductance subtype, G25, was 22 � 1 pS; the intermediate conductance channel, G35, was 33 � 1 pS; and the large conductance channel, G45, was 45 � 1 pS. The small channel was not antagonized significantly by Paraherquamide and was identified as the N-subtype. The intermediate channel was preferentially activated by levamisole rather than bephenium and antagonized by Paraherquamide: the intermediate channel was identified as the L-subtype. The large conductance channel was preferentially activated by bephenium, antagonized more by 2-desoxoparaherquamde than by Paraherquamide and was identified as the B-subtype. These observations reveal that the three channel subtypes have different selectivity for cholinergic anthelmintics. The different selectivity of these compounds should be considered when dealing with drug resistant infections.—Qian, H., Martin, R. J.
-
Parasitic Helminths - Discovery, Mode of Action, and Commercialization of Derquantel
Parasitic Helminths, 2012Co-Authors: Debra J. Woods, Alan P. Robertson, Richard J Martin, David P. Thompson, Timothy G. Geary, Steven J. Maeder, S. S. Johnson, George A. ConderAbstract:The frequent use of anthelmintics, particularly in geographic areas of intense parasite transmission, has led to the selection and spread of parasite strains that are resistant to them. Against that backdrop, Upjohn Animal Health (now Pfizer Animal Health) established a discovery program to identify compounds with novel modes of action and effective against several important nematode species, including strains resistant to the major classes of anthelmintics. This testing led to the discovery of 2-deoxy-Paraherquamide (derquantel) – the first of the spiroindole class of anthelmintics with commercial utility. Derquantel was prepared semisynthetically by chemical reduction of Paraherquamide, isolated from fermentation extracts of Penicillium simplicissimum. It was subsequently shown that derquantel is a nicotinic cholinergic antagonist. During clinical development, derquantel was combined with the macrocyclic lactone, abamectin. The combination of the new chemical with a second anthelmintic from a different chemical class in a single product (Startect) provides a more complete spectrum of anthelmintic activity and efficacy against resistant strains. Additionally, the combination also offers a means of minimizing selection for resistance to derquantel through the use of abamectin with a second, distinct mode of action, thereby potentially enhancing the sustainability of worm control programs.
-
Pharmacology of N-, L-, and B-subtypes of nematode nAChR resolved at the single-channel level in Ascaris suum
FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2006Co-Authors: Hai Qian, Richard J Martin, Alan P. RobertsonAbstract:Pharmacological experiments on Ascaris suum have demonstrated the presence of three (N-, L-, and B-) subtypes of cholinergic receptor mediating contraction of body wall muscle in parasitic nematodes. In the present study, these ionotropic acetylcholine (ACh) receptors (nAChRs) were activated by levamisole and bephenium under patch-clamp conditions and competitively antagonized by Paraherquamide and 2-desoxoParaherquamide. A number of recordings exhibited three separate current amplitude levels, indicating the presence of small, intermediate, and large conductance subtypes of receptor. The mean conductance of the small conductance subtype, G25, was 22 +/- 1 pS; the intermediate conductance channel, G35, was 33 +/- 1 pS; and the large conductance channel, G45, was 45 +/- 1 pS. The small channel was not antagonized significantly by Paraherquamide and was identified as the N-subtype. The intermediate channel was preferentially activated by levamisole rather than bephenium and antagonized by Paraherquamide: the intermediate channel was identified as the L-subtype. The large conductance channel was preferentially activated by bephenium, antagonized more by 2-desoxoparaherquamde than by Paraherquamide and was identified as the B-subtype. These observations reveal that the three channel subtypes have different selectivity for cholinergic anthelmintics. The different selectivity of these compounds should be considered when dealing with drug resistant infections.
-
Oxantel is an N-type (methyridine and nicotine) agonist not an L-type (levamisole and pyrantel) agonist: classification of cholinergic anthelmintics in Ascaris
International journal for parasitology, 2004Co-Authors: Richard J Martin, Sasa M. Trailovic, Cheryl L. Clark, Alan P. RobertsonAbstract:Abstract Three pharmacological subtypes of cholinergic receptors have been distinguished in Ascaris suum using a muscle contraction assay and classical pharmacological techniques. The receptor subtypes are: a B-subtype (sensitive to bephenium); an L-subtype (sensitive to levamisole and pyrantel); and an N-subtype (sensitive to nicotine and methyridine). Oxantel is a cholinergic anthelmintic that was first introduced for the treatment of whipworm, Trichuris, infections in children. Here, we compare the subtype selectivity of oxantel with thenium and other cholinergic anthelmintics. We used the A. suum assay to derive pA2 values for the agonists: oxantel, thenium, bephenium, levamisole, pyrantel, nicotine and methyridine with the antagonists: Paraherquamide, 2-desoxyParaherquamide and methyllycaconitine. pA2 values, rather than pKB values, were determined for all agonists when it was found that Schild slopes for some agonists were significantly less than 1.0. The pA2 of oxantel was 6.58±0.25 for Paraherquamide; 5.39±0.28 for 2-desoxyParaherquamide; 7.01±0.19 for methyllycaconitine. Comparison of pA2 values using cluster analysis showed that oxantel was grouped with nicotine and methyridine, the N-subtype agonists. Thenium had pA2s of 7.84±0.41 for Paraherquamide; 5.52±0.50 for 2-desoxyParaherquamide; 6.33±0.19 for methyllycaconitine. Cluster analysis placed thenium between the L-subtype agonists and the B-subtype agonist. The therapeutic significance of classification of cholinergic anthelmintics is discussed. Combination of oxantel and pyrantel would have therapeutic advantages, covering N- and L-subtypes, and so increasing spectrum of action and reducing the potential for development of resistance. Our results predict that oxantel may remain effective in some nematode isolates that have become levamisole- and pyrantel-resistant.
Rhona J. Cox - One of the best experts on this subject based on the ideXlab platform.
-
Asymmetric, Stereocontrolled Total Synthesis of Paraherquamide A
Journal of the American Chemical Society, 2003Co-Authors: Robert M. Williams, Jianhua Cao, Hidekazu Tsujishima, Rhona J. CoxAbstract:The first total synthesis of Paraherquamide A, a potent anthelmintic agent isolated from various Penicillium sp. with promising activity against drug-resistant intestinal parasites, is reported. Key steps in this asymmetric, stereocontrolled total synthesis include a new enantioselective synthesis of α-alkylated-β-hydroxyproline derivatives to access the substituted proline nucleus and a highly diastereoselective intramolecular SN2‘ cyclization to generate the core bicyclo[2.2.2]diazaoctane ring system.
-
Paraherquamides, brevianamides, and asperparalines: laboratory synthesis and biosynthesis. An interim report.
Accounts of chemical research, 2003Co-Authors: Robert M. Williams, Rhona J. CoxAbstract:Studies from our laboratories on the Paraherquamide, brevianamide, and asperparaline families of natural products are reviewed. It has been proposed that the unique core ring system that is common to this family of compounds arises by a biological intramolecular Diels-Alder cycloaddition reaction. Key biosynthetic studies are described, along with classical synthetic approaches as well as those inspired by Nature for the synthesis of these interesting molecules.
-
Synthetic studies towards Paraherquamide F: synthesis of the 1,7-dihydropyrano[2,3-g]indole ring system
Tetrahedron Letters, 2002Co-Authors: Rhona J. Cox, Robert M. WilliamsAbstract:A substituted 1,7-dihydropyrano[2,3-g]indole suitable for elaboration to Paraherquamide F has been prepared in eight steps and 6% overall yield. The key steps are a Fischer indolization and a Claisen rearrangement.
Wesley L. Shoop - One of the best experts on this subject based on the ideXlab platform.
-
DMD #19430 1
2016Co-Authors: Herve A. Aloysius, Wesley L. Shoop, Timothy A. Blizzard, Maria Silva V. Elipe, Byron H. Arison, Terry D. Faidley, Bruce F. Michael, Donald R. Thompson, Richard A. Tschirret-guth, At AAbstract:Comparative disposition and metabolism of Paraherquamide in sheep, gerbils and dogs
-
Comparative disposition and metabolism of Paraherquamide in sheep, gerbils and dogs
Drug metabolism and disposition: the biological fate of chemicals, 2008Co-Authors: Herve A. Aloysius, Wesley L. Shoop, B.f. Michael, Timothy A. Blizzard, Byron H. Arison, Maria Victoria Silva Elipe, Terry Faidley, Donald Thompson, Richard Tschirret-guthAbstract:The disposition and metabolism of Paraherquamide (PHQ), a potent and broad-spectrum anthelminthic, were examined in sheep, dogs, and gerbils. The metabolism of PHQ in these species was extensive and marked by significant species differences both in vitro and in vivo. In sheep and gerbils, PHQ metabolism occurs mainly at the pyrrolidine moiety, generating several metabolites that, for the most part, retained nematodicidal activity in vitro. In dogs, the dioxepene group was also extensively metabolized, ultimately resulting in formation of a catechol and loss of pharmacological activity. After oral administration of [3H]PHQ to intact sheep, gerbils, and dogs, the majority of the administered radioactivity was recovered in feces. Intact PHQ accounted for 0% (dogs) to ∼30% (sheep and gerbils) of drug-related material in feces. A detailed investigation of the composition of the intestinal content of sheep indicated that a significant amount of the dose was still present in the rumen 24 h after dose and that PHQ underwent significant dehydration in the cecum. The oral pharmacokinetic parameters of PHQ in sheep and dogs suggest that its absorption is rapid in both species but that its apparent elimination rate is significantly higher in the dog (t1/2 ∼ 1.5 h) than it is in sheep (t1/2 ∼ 8.5 h). The short elimination half-life and the absence of PHQ or other active components in the dog gastrointestinal tract provide a potential explanation of the lack of efficacy of PHQ in this species.
-
Evidence of multiple mechanisms of avermectin resistance in haemonchus contortus--comparison of selection protocols
International journal for parasitology, 1998Co-Authors: Jennifer H. Gill, Wesley L. Shoop, Caroline A. Kerr, Ernest LaceyAbstract:Abstract Three isolates of Haemonchus contortus selected for avermectin resistance in sheep were compared in three in vitro pharmacological tests previously shown to discriminate between field isolates of H. contortus resistant and susceptible to the avermectins. Two isolates, F7-A and IVC, were selected for avermectin resistance in the laboratory from a reference susceptible isolate using suboptimal doses of ivermectin (LD95) for 7 and 16 generations, respectively. In these isolates avermectin resistance was not associated with a decreased sensitivity to avermectin inhibition of larval development or L3 motility but was associated with an increased sensitivity to Paraherquamide. The third isolate, Warren, was derived from an overwhelmingly avermectin-susceptible, mixed species field isolate in a single generation by propagating the small number of survivors of a 0.2 mg/kg ivermectin treatment (i.e. 10×LD95). This isolate, like previously characterised avermectin-resistant H. contortus isolates derived from the field in South Africa and Australia, showed a markedly reduced sensitivity to avermectin inhibition of larval development and L3 motility, as well as an increased sensitivity to Paraherquamide. These results suggest that avermectin resistance can manifest itself in different ways and that the two selection protocols used to generate the F7-A, IVC and Warren isolates have resulted in the selection of different resistance phenotypes.
-
Anthelmintic activity of Paraherquamide in calves.
Veterinary parasitology, 1992Co-Authors: Wesley L. Shoop, B.f. Michael, H.w. Haines, C.h. EaryAbstract:Abstract Paraherquamide, an oxindole alkaloid metabolite of Penicillium paraherquei and Penicillium charlesii , was tested against the adult stages of nine common gastrointestinal and lung nematodes of calves at single, oral dosages of 0.5, 1.0, 2.0 or 4.0 mg kg −1 . At dosages 1.0–4.0 mg kg −1 there was 95% or more removal of Haemonchus placei, Ostertagia ostertagi, Trichostrongylus axei, Trichostrongylus colubriformis, Cooperia oncophora, Nematodirus helvetianus, Oesophagostomum radiatum , and Dictyocaulus viviparus. Cooperia punctata , the dosage-limiting species, was virtually unaffected by any dosage except the highest, which produced an efficacy of 89%. The 0.5 mg kg −1 dosage was 95% or more efficacious against H. placei, O. ostertagi, C. oncophora , and D. viviparus , but weaknessesb were evident against the other five species. No adverse reaction was observed in any calf.
-
The preparation and utilization of Paraherquamide-2-O-methyl imidate in the synthesis of 14-O-substituted Paraherquamide derivatives
Bioorganic & Medicinal Chemistry Letters, 1992Co-Authors: Peter J. Sinclair, Wesley L. Shoop, James M. Schaeffer, Helmut MrozikAbstract:Abstract The preparation of the methyl imidate of the antiparasitic oxindole alkaloid Paraherquamide, its utilization in the synthesis of a variety of 14-O-substituted parherquamide analogs and their biological activity are described.
