Synthetic studies of neoclerodane diterpenes from Salvia divinorum: Exploration of the 1-position

Kenneth G. Holden; Kevin Tidgewell; Alfred Marquam; Richard B. Rothman; Hernán Navarro; Thomas E. Prisinzano

doi:10.1016/j.bmcl.2007.09.050

Synthetic studies of neoclerodane diterpenes from Salvia divinorum: Exploration of the 1-position

Kenneth G. Holden, Kevin Tidgewell, Alfred Marquam, Richard B. Rothman, Hernán Navarro, Thomas E. Prisinzano

Research output: Contribution to journal › Article › peer-review

26 Scopus citations

Abstract

Modification of the C-1 ketone of salvinorin A (2a) produces analogues with opioid antagonist properties. Of particular significance is the finding that 1-deoxo-1,10-dehydrosalvinorin A (11a) is a moderately potent antagonist at all three opioid receptor subtypes, and that herkinorin (2b), a μ agonist, is converted to a weak antagonist by removal of the C-1 ketone (3b and 11b). These observations suggest that the ketone of 2b is a key structural feature responsible for μ agonist activity.

Original language	English
Pages (from-to)	6111-6115
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	17
Issue number	22
DOIs	https://doi.org/10.1016/j.bmcl.2007.09.050
State	Published - Nov 15 2007

Bibliographical note

Funding Information:
This work was supported by National Institutes of Health, National Institute on Drug Abuse Grant DA018151 (to T.E.P.). The authors also thank Keith Warner for technical assistance and the American Foundation for Pharmaceutical Education (K.T.) and the University of Iowa Graduate College (A.M.) for predoctoral fellowships.

Keywords

Antagonist
Opioid
Salvia divinorum
Salvinorin A
κ

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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10.1016/j.bmcl.2007.09.050

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title = "Synthetic studies of neoclerodane diterpenes from Salvia divinorum: Exploration of the 1-position",

abstract = "Modification of the C-1 ketone of salvinorin A (2a) produces analogues with opioid antagonist properties. Of particular significance is the finding that 1-deoxo-1,10-dehydrosalvinorin A (11a) is a moderately potent antagonist at all three opioid receptor subtypes, and that herkinorin (2b), a μ agonist, is converted to a weak antagonist by removal of the C-1 ketone (3b and 11b). These observations suggest that the ketone of 2b is a key structural feature responsible for μ agonist activity.",

keywords = "Antagonist, Opioid, Salvia divinorum, Salvinorin A, κ",

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note = "Funding Information: This work was supported by National Institutes of Health, National Institute on Drug Abuse Grant DA018151 (to T.E.P.). The authors also thank Keith Warner for technical assistance and the American Foundation for Pharmaceutical Education (K.T.) and the University of Iowa Graduate College (A.M.) for predoctoral fellowships. ",

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doi = "10.1016/j.bmcl.2007.09.050",

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AU - Tidgewell, Kevin

AU - Marquam, Alfred

AU - Rothman, Richard B.

AU - Navarro, Hernán

AU - Prisinzano, Thomas E.

N1 - Funding Information: This work was supported by National Institutes of Health, National Institute on Drug Abuse Grant DA018151 (to T.E.P.). The authors also thank Keith Warner for technical assistance and the American Foundation for Pharmaceutical Education (K.T.) and the University of Iowa Graduate College (A.M.) for predoctoral fellowships.

PY - 2007/11/15

Y1 - 2007/11/15

N2 - Modification of the C-1 ketone of salvinorin A (2a) produces analogues with opioid antagonist properties. Of particular significance is the finding that 1-deoxo-1,10-dehydrosalvinorin A (11a) is a moderately potent antagonist at all three opioid receptor subtypes, and that herkinorin (2b), a μ agonist, is converted to a weak antagonist by removal of the C-1 ketone (3b and 11b). These observations suggest that the ketone of 2b is a key structural feature responsible for μ agonist activity.

AB - Modification of the C-1 ketone of salvinorin A (2a) produces analogues with opioid antagonist properties. Of particular significance is the finding that 1-deoxo-1,10-dehydrosalvinorin A (11a) is a moderately potent antagonist at all three opioid receptor subtypes, and that herkinorin (2b), a μ agonist, is converted to a weak antagonist by removal of the C-1 ketone (3b and 11b). These observations suggest that the ketone of 2b is a key structural feature responsible for μ agonist activity.

KW - Antagonist

KW - Opioid

KW - Salvia divinorum

KW - Salvinorin A

KW - κ

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Synthetic studies of neoclerodane diterpenes from Salvia divinorum: Exploration of the 1-position

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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