Gordon Gribble - Academia.edu (original) (raw)
Papers by Gordon Gribble
Organic Preparations and Procedures International, 2018
Indolo[2,3-a]quinolizidine 1 (Scheme 1) has an interesting history. First synthesized by Keufer i... more Indolo[2,3-a]quinolizidine 1 (Scheme 1) has an interesting history. First synthesized by Keufer in 1950, this tetracyclic amine was subsequently prepared by several others, only later to be discovered as a naturally occurring plant alkaloid from the New Guinea tree Dracontomelum mangiferum. This represents a rare case of a natural product being discovered after its synthesis. Several enantioselective syntheses established the S-configuration for 1, although the isolated alkaloid was found to be partially racemic. Other syntheses have been reported. The 10-bromo derivative (arborescidine A) was isolated in 1993 from the marine tunicate Pseudodistoma arborescens, and, accordingly, 1 has been named desbromoarborescidine A. Despite myriad syntheses of 1, we felt that none are suitable for a large-scale preparation that we required for a project in our laboratory. We now describe a simple and atom-economical synthesis of (±)-1 from tryptophan (2) and dihydropyran (3) (Scheme 1). A classic Pictet-Spengler acid-catalyzed condensation of tryptophan (2) with 3,4-dihydro-2H-pyran (3) afforded 1-(4-hydroxybutyl)-1,2,3,4-tetrahydro-b-carboline-3-carboxylic acid (4) in yields up to 60%, presumably as a mixture of diastereomers (Scheme 2). Treatment of 4 with hot acidic potassium dichromate resulted in oxidative decarboxylation to afford 1-(4-hydroxybutyl)-b-carboline (5) in yields up to 89%. Treatment of carboline alcohol 5 with hydrogen bromide followed by sodium hydroxide yielded the ring-closed zwitterionic 7, via the bromide 6. Without isolation, the crude 7 was treated with sodium borohydride to give tetracyclic amine 1 in yields of up to 40–45% overall from tryptophan. In summary, we believe that this procedure is atom-economical and practical for preparing racemic 1,2,3,4,6,7,12,12b-octahydroindolo[2,3-a]quinolizine (1) both efficiently and on a reasonably large scale.
Organic Preparations and Procedures International, 2018
The title compound, 2-oxo-1,2,3,4,6,7,12,12b-Octahydroindolo[2,3-a]quinolizine (1), was first syn... more The title compound, 2-oxo-1,2,3,4,6,7,12,12b-Octahydroindolo[2,3-a]quinolizine (1), was first synthesized in 1952 by Groves and Swan as an entry point to the yohimbine-reserpine-corynantheine family of alkaloids. Subsequently, this indole ketone was prepared by several groups, and Kametani parlayed 1 into a synthesis of yohimbine. In connection with a project in our laboratory we required a short, efficient, and atom-economical preparation of 1. Of the several known syntheses of 1 only the method of Potts and Nasri seemed suitable for us. We now describe a modification of this synthesis that involves the coupling of 3-acetylindole (2) and 4-methoxypyridine (3) (Scheme 1).
The Journal of Organic Chemistry, 2016
A three-step synthesis of masked 2,3-diaminoindole 1 from 2-iodo-3-nitro-1-(phenylsulfonyl)indole... more A three-step synthesis of masked 2,3-diaminoindole 1 from 2-iodo-3-nitro-1-(phenylsulfonyl)indole (2) has been developed. Treatment of 1 with trifluoroacetic acid generates the unstable 2,3-diamino-1-(phenylsulfonyl)indole (3), which can be trapped with α-dicarbonyl compounds to afford 5H-pyrazino[2,3-b]indoles 7-10.
Chemosphere, Jan 6, 2016
The US military is developing insensitive munitions (IM) that are less sensitive to shock and hig... more The US military is developing insensitive munitions (IM) that are less sensitive to shock and high temperatures to minimize unintentional detonations. DNAN (2,4-dinitroanisole) is one of the main ingredients of these IM formulations. During live-fire training, chunks of IM formulations are scattered by partial detonations and, once on the soil, they weather and dissolve. DNAN changes color when exposed to sunlight suggesting that it photodegrades into other compounds. We investigated the photo-degradation of DNAN both as a pure solid and as part of solid IM formulations, IMX101, IMX104 and PAX21. The concentrations of degradation products found were small, <1%, relative to DNAN concentrations. We saw transient peaks in the chromatograms indicating intermediate, unstable products but we consistently found methoxy nitrophenols and methoxy nitroanilines. We also found one unknown in most of the samples and other unknowns less frequently.
Tetrahedron Letters, 2011
Environmental Chemistry, 2015
Environmental context The general perception that nature does not produce compounds containing ha... more Environmental context The general perception that nature does not produce compounds containing halogens – chlorine, bromine, iodine and fluorine – is now known to be erroneous. Modern isolation and identification techniques have led to the discovery of more than 5000 halogen-containing compounds from myriad marine and terrestrial plant and animal sources. Many of these compounds possess extraordinary biological activity, including anticancer, antiviral and antibacterial activity of potential human benefit. This short review presents the naturally occurring organohalogen compounds discovered and characterised in 2014. They include compounds from both marine and terrestrial organisms, such as algae, sponges, corals, tunicates, bryozoans, fungi, bacteria, cyanobacteria and plants. Several novel structural types have been characterised. From only ~24 in 1968, naturally occurring organohalogens currently number more than 5000, and they continue to be discovered in all regions of the worl...
The Journal of Organic Chemistry, 2015
Pharmacological research : the official journal of the Italian Pharmacological Society, Jan 31, 2015
Two new analogues of CDDO-Imidazolide (CDDO-Im), namely 1-[2-Cyano-3,12-dioxooleana-1,9(11)-dien-... more Two new analogues of CDDO-Imidazolide (CDDO-Im), namely 1-[2-Cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl]-4(-pyridin-2-yl)-1H-imidazole ("CDDO-2P-Im") and 1-[2-Cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl]-4(-pyridin-3-yl)-1H-imidazole ("CDDO-3P-Im") have been synthesized and tested for their potential use as chemopreventive drugs. At nanomolar concentrations, they were equipotent to CDDO-Im for inducing differentiation and apoptosis in U937 leukemia cells. As inflammation and oxidative stress contribute to carcinogenesis, we also assessed their cytoprotective potential. The new compounds suppressed inducible nitric oxide synthase (iNOS) expression in RAW264.7 macrophage-like cells and significantly elevated heme oxygenase-1 (HO-1) and quinone reductase (NQO1) mRNA and protein levels in various mouse tissues in vivo. Most importantly, pharmacokinetic studies performed in vitro in human plasma and in vivo showed that each new analogue was more stable than CDDO-Im. Mu...
Fortschritte der Chemie organischer Naturstoffe = Progress in the chemistry of organic natural products. Progrès dans la chimie des substances organiques naturelles, 2010
ABSTRACT While the question of how nature produces organohalogens lagged far behind their discove... more ABSTRACT While the question of how nature produces organohalogens lagged far behind their discovery, this situation has dramatically changed since the first review (1). Numerous excellent reviews of biohalogenation are available (17, 59, 2114–2122, 2323), and, as will be seen, several new halogen peroxidases, halogenases, and other enzymes capable of introducing halogen into organic compounds are known, including fluorine. Specialized reviews on biohalogenation involving vanadium haloperoxidases (2123–2126), biochlorination (2127), biohalogenation by Basidiomycetes fungi (2128), haloperoxidases in organic synthesis (2129–2131, 2327), biohalogenation enzymatic mechanisms (2132), and halomethane biosynthesis (2133) are available. The role of hydrogen peroxide in defining the function of haloperoxidases and other plant enzymes has also been investigated (2134–2137).
Organic preparations and procedures international, 2005
The Handbook of Environmental Chemistry, 2003
Tetrahedron Letters, 2011
Tetrahedron Letters, 2010
Synthesis, 1977
communication, Synthesis 1977; 1977(3): 172-176 DOI: 10.1055/s-1977-24308. © Georg Thieme Verlag,... more communication, Synthesis 1977; 1977(3): 172-176 DOI: 10.1055/s-1977-24308. © Georg Thieme Verlag, Rüdigerstr. 14, 70469 Stuttgart, Germany. All rights reserved. This journal, including all individual contributions and illustrations ...
Organic Preparations and Procedures International, 2008
Of the more than 4,500 known naturally occurring organohalogen compounds' the halogenated bip... more Of the more than 4,500 known naturally occurring organohalogen compounds' the halogenated bipyrroles are among the most interesting. For example, hexabromo1 ,I1-dimethyl22'-bipyrrole and 3,3',4,4'-tetrabromo-5J1-dichloro1 ,11-dimethyl-2,2'-bipyrrole are present in the eggs of Pacific and Atlantic Ocean seabirds (albatross, puffin, gull, petrel, auklet) and in bald eagle liver samples?" and, more recently, 2,3,31,4,4',5,5'-heptachloro-11-methyl1,2'-bipyrrole (designated "QI") (1) is found to be a ubiquitous marine natural product, detected in over 100 environmental marine samples from virtually all over the world (sea bird eggs, fish, the blubber of marine mammals, Antarctic air, and, remarkably, human milk from Eskimo women who consume whale blubber): Atthough we established the structure of Q1 by total synthesis in 2002, the yield was very low due to the difficulty of synthesis and instability of the key intermediate 1,2'-bipyrrolyl 4.5 Subsequently, many mixed halogenated 1,2'-bipyrrolyls have been detected in a myriad of marine sources! For example, 2,3,3',4,4',5,5'-heptabromo-l'-methyl-l,2'bipyrrole (2) was tentatively identified in 2006.6b9c To provide a more efficient synthesis of Q1 (1) for much needed analytical comparison and biological evaluation in view of its structural similarity to anthropogenic polychlorinated
Natural Product Research, 2008
The known cembranoid diterpene eunicin (1) was isolated from a new genus of octocoral, Pseudoplex... more The known cembranoid diterpene eunicin (1) was isolated from a new genus of octocoral, Pseudoplexaura, collected in the Caribbean. The complete assignment of the 13C and 1H NMR spectra, including differentiation of pro-R and pro-S hydrogens and elucidation of all J values, was accomplished with the aid of TOCSY, HSQC, and HMBC data, and a consideration of three low-energy conformations using SYBYL.
The Journal of Organic Chemistry
Organic Preparations and Procedures International, 2018
Indolo[2,3-a]quinolizidine 1 (Scheme 1) has an interesting history. First synthesized by Keufer i... more Indolo[2,3-a]quinolizidine 1 (Scheme 1) has an interesting history. First synthesized by Keufer in 1950, this tetracyclic amine was subsequently prepared by several others, only later to be discovered as a naturally occurring plant alkaloid from the New Guinea tree Dracontomelum mangiferum. This represents a rare case of a natural product being discovered after its synthesis. Several enantioselective syntheses established the S-configuration for 1, although the isolated alkaloid was found to be partially racemic. Other syntheses have been reported. The 10-bromo derivative (arborescidine A) was isolated in 1993 from the marine tunicate Pseudodistoma arborescens, and, accordingly, 1 has been named desbromoarborescidine A. Despite myriad syntheses of 1, we felt that none are suitable for a large-scale preparation that we required for a project in our laboratory. We now describe a simple and atom-economical synthesis of (±)-1 from tryptophan (2) and dihydropyran (3) (Scheme 1). A classic Pictet-Spengler acid-catalyzed condensation of tryptophan (2) with 3,4-dihydro-2H-pyran (3) afforded 1-(4-hydroxybutyl)-1,2,3,4-tetrahydro-b-carboline-3-carboxylic acid (4) in yields up to 60%, presumably as a mixture of diastereomers (Scheme 2). Treatment of 4 with hot acidic potassium dichromate resulted in oxidative decarboxylation to afford 1-(4-hydroxybutyl)-b-carboline (5) in yields up to 89%. Treatment of carboline alcohol 5 with hydrogen bromide followed by sodium hydroxide yielded the ring-closed zwitterionic 7, via the bromide 6. Without isolation, the crude 7 was treated with sodium borohydride to give tetracyclic amine 1 in yields of up to 40–45% overall from tryptophan. In summary, we believe that this procedure is atom-economical and practical for preparing racemic 1,2,3,4,6,7,12,12b-octahydroindolo[2,3-a]quinolizine (1) both efficiently and on a reasonably large scale.
Organic Preparations and Procedures International, 2018
The title compound, 2-oxo-1,2,3,4,6,7,12,12b-Octahydroindolo[2,3-a]quinolizine (1), was first syn... more The title compound, 2-oxo-1,2,3,4,6,7,12,12b-Octahydroindolo[2,3-a]quinolizine (1), was first synthesized in 1952 by Groves and Swan as an entry point to the yohimbine-reserpine-corynantheine family of alkaloids. Subsequently, this indole ketone was prepared by several groups, and Kametani parlayed 1 into a synthesis of yohimbine. In connection with a project in our laboratory we required a short, efficient, and atom-economical preparation of 1. Of the several known syntheses of 1 only the method of Potts and Nasri seemed suitable for us. We now describe a modification of this synthesis that involves the coupling of 3-acetylindole (2) and 4-methoxypyridine (3) (Scheme 1).
The Journal of Organic Chemistry, 2016
A three-step synthesis of masked 2,3-diaminoindole 1 from 2-iodo-3-nitro-1-(phenylsulfonyl)indole... more A three-step synthesis of masked 2,3-diaminoindole 1 from 2-iodo-3-nitro-1-(phenylsulfonyl)indole (2) has been developed. Treatment of 1 with trifluoroacetic acid generates the unstable 2,3-diamino-1-(phenylsulfonyl)indole (3), which can be trapped with α-dicarbonyl compounds to afford 5H-pyrazino[2,3-b]indoles 7-10.
Chemosphere, Jan 6, 2016
The US military is developing insensitive munitions (IM) that are less sensitive to shock and hig... more The US military is developing insensitive munitions (IM) that are less sensitive to shock and high temperatures to minimize unintentional detonations. DNAN (2,4-dinitroanisole) is one of the main ingredients of these IM formulations. During live-fire training, chunks of IM formulations are scattered by partial detonations and, once on the soil, they weather and dissolve. DNAN changes color when exposed to sunlight suggesting that it photodegrades into other compounds. We investigated the photo-degradation of DNAN both as a pure solid and as part of solid IM formulations, IMX101, IMX104 and PAX21. The concentrations of degradation products found were small, <1%, relative to DNAN concentrations. We saw transient peaks in the chromatograms indicating intermediate, unstable products but we consistently found methoxy nitrophenols and methoxy nitroanilines. We also found one unknown in most of the samples and other unknowns less frequently.
Tetrahedron Letters, 2011
Environmental Chemistry, 2015
Environmental context The general perception that nature does not produce compounds containing ha... more Environmental context The general perception that nature does not produce compounds containing halogens – chlorine, bromine, iodine and fluorine – is now known to be erroneous. Modern isolation and identification techniques have led to the discovery of more than 5000 halogen-containing compounds from myriad marine and terrestrial plant and animal sources. Many of these compounds possess extraordinary biological activity, including anticancer, antiviral and antibacterial activity of potential human benefit. This short review presents the naturally occurring organohalogen compounds discovered and characterised in 2014. They include compounds from both marine and terrestrial organisms, such as algae, sponges, corals, tunicates, bryozoans, fungi, bacteria, cyanobacteria and plants. Several novel structural types have been characterised. From only ~24 in 1968, naturally occurring organohalogens currently number more than 5000, and they continue to be discovered in all regions of the worl...
The Journal of Organic Chemistry, 2015
Pharmacological research : the official journal of the Italian Pharmacological Society, Jan 31, 2015
Two new analogues of CDDO-Imidazolide (CDDO-Im), namely 1-[2-Cyano-3,12-dioxooleana-1,9(11)-dien-... more Two new analogues of CDDO-Imidazolide (CDDO-Im), namely 1-[2-Cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl]-4(-pyridin-2-yl)-1H-imidazole ("CDDO-2P-Im") and 1-[2-Cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl]-4(-pyridin-3-yl)-1H-imidazole ("CDDO-3P-Im") have been synthesized and tested for their potential use as chemopreventive drugs. At nanomolar concentrations, they were equipotent to CDDO-Im for inducing differentiation and apoptosis in U937 leukemia cells. As inflammation and oxidative stress contribute to carcinogenesis, we also assessed their cytoprotective potential. The new compounds suppressed inducible nitric oxide synthase (iNOS) expression in RAW264.7 macrophage-like cells and significantly elevated heme oxygenase-1 (HO-1) and quinone reductase (NQO1) mRNA and protein levels in various mouse tissues in vivo. Most importantly, pharmacokinetic studies performed in vitro in human plasma and in vivo showed that each new analogue was more stable than CDDO-Im. Mu...
Fortschritte der Chemie organischer Naturstoffe = Progress in the chemistry of organic natural products. Progrès dans la chimie des substances organiques naturelles, 2010
ABSTRACT While the question of how nature produces organohalogens lagged far behind their discove... more ABSTRACT While the question of how nature produces organohalogens lagged far behind their discovery, this situation has dramatically changed since the first review (1). Numerous excellent reviews of biohalogenation are available (17, 59, 2114–2122, 2323), and, as will be seen, several new halogen peroxidases, halogenases, and other enzymes capable of introducing halogen into organic compounds are known, including fluorine. Specialized reviews on biohalogenation involving vanadium haloperoxidases (2123–2126), biochlorination (2127), biohalogenation by Basidiomycetes fungi (2128), haloperoxidases in organic synthesis (2129–2131, 2327), biohalogenation enzymatic mechanisms (2132), and halomethane biosynthesis (2133) are available. The role of hydrogen peroxide in defining the function of haloperoxidases and other plant enzymes has also been investigated (2134–2137).
Organic preparations and procedures international, 2005
The Handbook of Environmental Chemistry, 2003
Tetrahedron Letters, 2011
Tetrahedron Letters, 2010
Synthesis, 1977
communication, Synthesis 1977; 1977(3): 172-176 DOI: 10.1055/s-1977-24308. © Georg Thieme Verlag,... more communication, Synthesis 1977; 1977(3): 172-176 DOI: 10.1055/s-1977-24308. © Georg Thieme Verlag, Rüdigerstr. 14, 70469 Stuttgart, Germany. All rights reserved. This journal, including all individual contributions and illustrations ...
Organic Preparations and Procedures International, 2008
Of the more than 4,500 known naturally occurring organohalogen compounds' the halogenated bip... more Of the more than 4,500 known naturally occurring organohalogen compounds' the halogenated bipyrroles are among the most interesting. For example, hexabromo1 ,I1-dimethyl22'-bipyrrole and 3,3',4,4'-tetrabromo-5J1-dichloro1 ,11-dimethyl-2,2'-bipyrrole are present in the eggs of Pacific and Atlantic Ocean seabirds (albatross, puffin, gull, petrel, auklet) and in bald eagle liver samples?" and, more recently, 2,3,31,4,4',5,5'-heptachloro-11-methyl1,2'-bipyrrole (designated "QI") (1) is found to be a ubiquitous marine natural product, detected in over 100 environmental marine samples from virtually all over the world (sea bird eggs, fish, the blubber of marine mammals, Antarctic air, and, remarkably, human milk from Eskimo women who consume whale blubber): Atthough we established the structure of Q1 by total synthesis in 2002, the yield was very low due to the difficulty of synthesis and instability of the key intermediate 1,2'-bipyrrolyl 4.5 Subsequently, many mixed halogenated 1,2'-bipyrrolyls have been detected in a myriad of marine sources! For example, 2,3,3',4,4',5,5'-heptabromo-l'-methyl-l,2'bipyrrole (2) was tentatively identified in 2006.6b9c To provide a more efficient synthesis of Q1 (1) for much needed analytical comparison and biological evaluation in view of its structural similarity to anthropogenic polychlorinated
Natural Product Research, 2008
The known cembranoid diterpene eunicin (1) was isolated from a new genus of octocoral, Pseudoplex... more The known cembranoid diterpene eunicin (1) was isolated from a new genus of octocoral, Pseudoplexaura, collected in the Caribbean. The complete assignment of the 13C and 1H NMR spectra, including differentiation of pro-R and pro-S hydrogens and elucidation of all J values, was accomplished with the aid of TOCSY, HSQC, and HMBC data, and a consideration of three low-energy conformations using SYBYL.
The Journal of Organic Chemistry