The Experts below are selected from a list of 69 Experts worldwide ranked by ideXlab platform
Glenn C. Micalizio - One of the best experts on this subject based on the ideXlab platform.
-
Synthesis of conolidine, a potent non-opioid analgesic for tonic and persistent pain
Nature Chemistry, 2011Co-Authors: Michael A. Tarselli, Kirsten M. Raehal, Alex K. Brasher, John M. Streicher, Chad E. Groer, Michael D. Cameron, Laura M. Bohn, Glenn C. MicalizioAbstract:Management of chronic pain continues to represent an area of great unmet biomedical need. Although opioid analgesics are typically embraced as the mainstay of pharmaceutical interventions in this area, they suffer from substantial liabilities that include addiction and tolerance, as well as depression of breathing, nausea and chronic constipation. Because of their suboptimal therapeutic profile, the search for non-opioid analgesics to replace these well-established therapeutics is an important pursuit. Conolidine is a rare C5-nor Stemmadenine natural product recently isolated from the stem bark of Tabernaemontana divaricata (a tropical flowering plant used in traditional Chinese, Ayurvedic and Thai medicine). Although structurally related alkaloids have been described as opioid analgesics, no therapeutically relevant properties of conolidine have previously been reported. Here, we describe the first de novo synthetic pathway to this exceptionally rare C5-nor Stemmadenine natural product, the first asymmetric synthesis of any member of this natural product class, and the discovery that (±)-, (+)- and (−)-conolidine are potent and efficacious non-opioid analgesics in an in vivo model of tonic and persistent pain. The first total synthesis of conolidine — representing the first asymmetric synthesis of a C5-nor-Stemmadenine — is described. The chemical synthesis proceeds in just nine steps and gives an 18% overall yield from a commercially available pyridine — an achievement that led to the discovery that (+)-, (–)- and (±)-conolidine are potent non-opioid analgesics.
-
synthesis of conolidine a potent non opioid analgesic for tonic and persistent pain
Nature Chemistry, 2011Co-Authors: Michael A. Tarselli, Kirsten M. Raehal, Alex K. Brasher, John M. Streicher, Chad E. Groer, Michael D. Cameron, Laura M. Bohn, Glenn C. MicalizioAbstract:Management of chronic pain continues to represent an area of great unmet biomedical need. Although opioid analgesics are typically embraced as the mainstay of pharmaceutical interventions in this area, they suffer from substantial liabilities that include addiction and tolerance, as well as depression of breathing, nausea and chronic constipation. Because of their suboptimal therapeutic profile, the search for non-opioid analgesics to replace these well-established therapeutics is an important pursuit. Conolidine is a rare C5-nor Stemmadenine natural product recently isolated from the stem bark of Tabernaemontana divaricata (a tropical flowering plant used in traditional Chinese, Ayurvedic and Thai medicine). Although structurally related alkaloids have been described as opioid analgesics, no therapeutically relevant properties of conolidine have previously been reported. Here, we describe the first de novo synthetic pathway to this exceptionally rare C5-nor Stemmadenine natural product, the first asymmetric synthesis of any member of this natural product class, and the discovery that (±)-, (+)- and (-)-conolidine are potent and efficacious non-opioid analgesics in an in vivo model of tonic and persistent pain.
Michael A. Tarselli - One of the best experts on this subject based on the ideXlab platform.
-
Synthesis of conolidine, a potent non-opioid analgesic for tonic and persistent pain
Nature Chemistry, 2011Co-Authors: Michael A. Tarselli, Kirsten M. Raehal, Alex K. Brasher, John M. Streicher, Chad E. Groer, Michael D. Cameron, Laura M. Bohn, Glenn C. MicalizioAbstract:Management of chronic pain continues to represent an area of great unmet biomedical need. Although opioid analgesics are typically embraced as the mainstay of pharmaceutical interventions in this area, they suffer from substantial liabilities that include addiction and tolerance, as well as depression of breathing, nausea and chronic constipation. Because of their suboptimal therapeutic profile, the search for non-opioid analgesics to replace these well-established therapeutics is an important pursuit. Conolidine is a rare C5-nor Stemmadenine natural product recently isolated from the stem bark of Tabernaemontana divaricata (a tropical flowering plant used in traditional Chinese, Ayurvedic and Thai medicine). Although structurally related alkaloids have been described as opioid analgesics, no therapeutically relevant properties of conolidine have previously been reported. Here, we describe the first de novo synthetic pathway to this exceptionally rare C5-nor Stemmadenine natural product, the first asymmetric synthesis of any member of this natural product class, and the discovery that (±)-, (+)- and (−)-conolidine are potent and efficacious non-opioid analgesics in an in vivo model of tonic and persistent pain. The first total synthesis of conolidine — representing the first asymmetric synthesis of a C5-nor-Stemmadenine — is described. The chemical synthesis proceeds in just nine steps and gives an 18% overall yield from a commercially available pyridine — an achievement that led to the discovery that (+)-, (–)- and (±)-conolidine are potent non-opioid analgesics.
-
synthesis of conolidine a potent non opioid analgesic for tonic and persistent pain
Nature Chemistry, 2011Co-Authors: Michael A. Tarselli, Kirsten M. Raehal, Alex K. Brasher, John M. Streicher, Chad E. Groer, Michael D. Cameron, Laura M. Bohn, Glenn C. MicalizioAbstract:Management of chronic pain continues to represent an area of great unmet biomedical need. Although opioid analgesics are typically embraced as the mainstay of pharmaceutical interventions in this area, they suffer from substantial liabilities that include addiction and tolerance, as well as depression of breathing, nausea and chronic constipation. Because of their suboptimal therapeutic profile, the search for non-opioid analgesics to replace these well-established therapeutics is an important pursuit. Conolidine is a rare C5-nor Stemmadenine natural product recently isolated from the stem bark of Tabernaemontana divaricata (a tropical flowering plant used in traditional Chinese, Ayurvedic and Thai medicine). Although structurally related alkaloids have been described as opioid analgesics, no therapeutically relevant properties of conolidine have previously been reported. Here, we describe the first de novo synthetic pathway to this exceptionally rare C5-nor Stemmadenine natural product, the first asymmetric synthesis of any member of this natural product class, and the discovery that (±)-, (+)- and (-)-conolidine are potent and efficacious non-opioid analgesics in an in vivo model of tonic and persistent pain.
Vincenzo De Luca - One of the best experts on this subject based on the ideXlab platform.
-
Solution of the multistep pathway for assembly of corynanthean, strychnos, iboga, and aspidosperma monoterpenoid indole alkaloids from 19E-geissoschizine
Proceedings of the National Academy of Sciences of the United States of America, 2018Co-Authors: Michael E. A. M. Easson, Razvan Simionescu, Josef Hajicek, Antje M. K. Thamm, Vonny Salim, Vincenzo De LucaAbstract:Monoterpenoid indole alkaloids (MIAs) possess a diversity of alkaloid skeletons whose biosynthesis is poorly understood. A bioinformatic search of candidate genes, combined with their virus-induced gene silencing, targeted MIA profiling and in vitro/in vivo pathway reconstitution identified and functionally characterized six genes as well as a seventh enzyme reaction required for the conversion of 19E-geissoschizine to tabersonine and catharanthine. The involvement of pathway intermediates in the formation of four MIA skeletons is described, and the role of Stemmadenine-O-acetylation in providing necessary reactive substrates for the formation of iboga and aspidosperma MIAs is described. The results enable the assembly of complex dimeric MIAs used in cancer chemotherapy and open the way to production of many other biologically active MIAs that are not easily available from nature.
-
monoterpene indole alkaloids from the fruit of tabernaemontana litoralis and differential alkaloid composition in various fruit components
Journal of Natural Products, 2016Co-Authors: Razvan Simonescu, Vincenzo De LucaAbstract:Two new monoterpene indole alkaloids, isoakuammiline (1) and 18-hydroxypseudovincadifformine (2), and five known alkaloids, coronaridine (3), heyneanine (4), 3,19-oxidocoronaridine (5), tabersonine, and strictosidine, were identified from the fruit of Tabernaemontana litoralis. The structures of the alkaloids were determined using NMR and MS data analyses. While 18-hydroxypseudovincadifformine (2) showed a new hydroxylation pattern, isoakuammiline (1) revealed a novel skeleton for monoterpene indole alkaloids. In spite of the isolation of Stemmadenine from the fruit tissues in other Tabernaemontana species, this vital biosynthetic precursor of iboga, aspidosperma, and pseudoaspidosperma skeletons was not found in T. litoralis.
Kirsten M. Raehal - One of the best experts on this subject based on the ideXlab platform.
-
Synthesis of conolidine, a potent non-opioid analgesic for tonic and persistent pain
Nature Chemistry, 2011Co-Authors: Michael A. Tarselli, Kirsten M. Raehal, Alex K. Brasher, John M. Streicher, Chad E. Groer, Michael D. Cameron, Laura M. Bohn, Glenn C. MicalizioAbstract:Management of chronic pain continues to represent an area of great unmet biomedical need. Although opioid analgesics are typically embraced as the mainstay of pharmaceutical interventions in this area, they suffer from substantial liabilities that include addiction and tolerance, as well as depression of breathing, nausea and chronic constipation. Because of their suboptimal therapeutic profile, the search for non-opioid analgesics to replace these well-established therapeutics is an important pursuit. Conolidine is a rare C5-nor Stemmadenine natural product recently isolated from the stem bark of Tabernaemontana divaricata (a tropical flowering plant used in traditional Chinese, Ayurvedic and Thai medicine). Although structurally related alkaloids have been described as opioid analgesics, no therapeutically relevant properties of conolidine have previously been reported. Here, we describe the first de novo synthetic pathway to this exceptionally rare C5-nor Stemmadenine natural product, the first asymmetric synthesis of any member of this natural product class, and the discovery that (±)-, (+)- and (−)-conolidine are potent and efficacious non-opioid analgesics in an in vivo model of tonic and persistent pain. The first total synthesis of conolidine — representing the first asymmetric synthesis of a C5-nor-Stemmadenine — is described. The chemical synthesis proceeds in just nine steps and gives an 18% overall yield from a commercially available pyridine — an achievement that led to the discovery that (+)-, (–)- and (±)-conolidine are potent non-opioid analgesics.
-
synthesis of conolidine a potent non opioid analgesic for tonic and persistent pain
Nature Chemistry, 2011Co-Authors: Michael A. Tarselli, Kirsten M. Raehal, Alex K. Brasher, John M. Streicher, Chad E. Groer, Michael D. Cameron, Laura M. Bohn, Glenn C. MicalizioAbstract:Management of chronic pain continues to represent an area of great unmet biomedical need. Although opioid analgesics are typically embraced as the mainstay of pharmaceutical interventions in this area, they suffer from substantial liabilities that include addiction and tolerance, as well as depression of breathing, nausea and chronic constipation. Because of their suboptimal therapeutic profile, the search for non-opioid analgesics to replace these well-established therapeutics is an important pursuit. Conolidine is a rare C5-nor Stemmadenine natural product recently isolated from the stem bark of Tabernaemontana divaricata (a tropical flowering plant used in traditional Chinese, Ayurvedic and Thai medicine). Although structurally related alkaloids have been described as opioid analgesics, no therapeutically relevant properties of conolidine have previously been reported. Here, we describe the first de novo synthetic pathway to this exceptionally rare C5-nor Stemmadenine natural product, the first asymmetric synthesis of any member of this natural product class, and the discovery that (±)-, (+)- and (-)-conolidine are potent and efficacious non-opioid analgesics in an in vivo model of tonic and persistent pain.
Michael D. Cameron - One of the best experts on this subject based on the ideXlab platform.
-
Synthesis of conolidine, a potent non-opioid analgesic for tonic and persistent pain
Nature Chemistry, 2011Co-Authors: Michael A. Tarselli, Kirsten M. Raehal, Alex K. Brasher, John M. Streicher, Chad E. Groer, Michael D. Cameron, Laura M. Bohn, Glenn C. MicalizioAbstract:Management of chronic pain continues to represent an area of great unmet biomedical need. Although opioid analgesics are typically embraced as the mainstay of pharmaceutical interventions in this area, they suffer from substantial liabilities that include addiction and tolerance, as well as depression of breathing, nausea and chronic constipation. Because of their suboptimal therapeutic profile, the search for non-opioid analgesics to replace these well-established therapeutics is an important pursuit. Conolidine is a rare C5-nor Stemmadenine natural product recently isolated from the stem bark of Tabernaemontana divaricata (a tropical flowering plant used in traditional Chinese, Ayurvedic and Thai medicine). Although structurally related alkaloids have been described as opioid analgesics, no therapeutically relevant properties of conolidine have previously been reported. Here, we describe the first de novo synthetic pathway to this exceptionally rare C5-nor Stemmadenine natural product, the first asymmetric synthesis of any member of this natural product class, and the discovery that (±)-, (+)- and (−)-conolidine are potent and efficacious non-opioid analgesics in an in vivo model of tonic and persistent pain. The first total synthesis of conolidine — representing the first asymmetric synthesis of a C5-nor-Stemmadenine — is described. The chemical synthesis proceeds in just nine steps and gives an 18% overall yield from a commercially available pyridine — an achievement that led to the discovery that (+)-, (–)- and (±)-conolidine are potent non-opioid analgesics.
-
synthesis of conolidine a potent non opioid analgesic for tonic and persistent pain
Nature Chemistry, 2011Co-Authors: Michael A. Tarselli, Kirsten M. Raehal, Alex K. Brasher, John M. Streicher, Chad E. Groer, Michael D. Cameron, Laura M. Bohn, Glenn C. MicalizioAbstract:Management of chronic pain continues to represent an area of great unmet biomedical need. Although opioid analgesics are typically embraced as the mainstay of pharmaceutical interventions in this area, they suffer from substantial liabilities that include addiction and tolerance, as well as depression of breathing, nausea and chronic constipation. Because of their suboptimal therapeutic profile, the search for non-opioid analgesics to replace these well-established therapeutics is an important pursuit. Conolidine is a rare C5-nor Stemmadenine natural product recently isolated from the stem bark of Tabernaemontana divaricata (a tropical flowering plant used in traditional Chinese, Ayurvedic and Thai medicine). Although structurally related alkaloids have been described as opioid analgesics, no therapeutically relevant properties of conolidine have previously been reported. Here, we describe the first de novo synthetic pathway to this exceptionally rare C5-nor Stemmadenine natural product, the first asymmetric synthesis of any member of this natural product class, and the discovery that (±)-, (+)- and (-)-conolidine are potent and efficacious non-opioid analgesics in an in vivo model of tonic and persistent pain.