Piperidine dispiro-1,2,4-trioxane analogues

Sunil Sabbani; Paul A. Stocks; Gemma L. Ellis; Jill Davies; Erik Hedenstrom; Steve Ward; Paul M. O'Neill

doi:10.1016/j.bmcl.2008.09.052

Piperidine dispiro-1,2,4-trioxane analogues

Sunil Sabbani, Paul A. Stocks, Gemma L. Ellis, Jill Davies, Erik Hedenstrom, Steve Ward, Paul M. O'Neill

Tropical Disease Biology

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

31 Citations (Scopus)

Abstract

Dispiro N-Boc-protected 1,2,4-trioxane 2 was synthesised via Mo(acac)(2) catalysed perhydrolysis of N-Boc spirooxirane followed by condensation of the resulting beta-hydroperoxy alcohol 10 with 2-adamantanone. N-Boc 1,2,4-trioxane 2 was converted to the amine 1,2,4-trioxane hydrochloride salt 3 which was subsequently used to prepare derivatives (4-7). Several of these novel 1,2,4-trioxanes had nanomolar antimalarial activity versus the 3D7 strain of Plasmodium falciparum. Amine intermediate 3 represents a versatile derivative for the preparation of achiral arrays of trioxane analogues with antimalarial activity. (C) 2008 Elsevier Ltd. All rights reserved.

Original language	English
Pages (from-to)	5804-5808
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	18
Issue number	21
DOIs	https://doi.org/10.1016/j.bmcl.2008.09.052
Publication status	Published - 1 Nov 2008

Keywords

1,2,4-Trioxane
Antimalarial
Endoperoxide
Hydrogen peroxide
Mechanism of action

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10.1016/j.bmcl.2008.09.052

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@article{1415d2a5dd444f0caf00817a56114b47,

title = "Piperidine dispiro-1,2,4-trioxane analogues",

abstract = "Dispiro N-Boc-protected 1,2,4-trioxane 2 was synthesised via Mo(acac)(2) catalysed perhydrolysis of N-Boc spirooxirane followed by condensation of the resulting beta-hydroperoxy alcohol 10 with 2-adamantanone. N-Boc 1,2,4-trioxane 2 was converted to the amine 1,2,4-trioxane hydrochloride salt 3 which was subsequently used to prepare derivatives (4-7). Several of these novel 1,2,4-trioxanes had nanomolar antimalarial activity versus the 3D7 strain of Plasmodium falciparum. Amine intermediate 3 represents a versatile derivative for the preparation of achiral arrays of trioxane analogues with antimalarial activity. (C) 2008 Elsevier Ltd. All rights reserved.",

keywords = "1,2,4-Trioxane, Antimalarial, Endoperoxide, Hydrogen peroxide, Mechanism of action",

author = "Sunil Sabbani and Stocks, \{Paul A.\} and Ellis, \{Gemma L.\} and Jill Davies and Erik Hedenstrom and Steve Ward and O'Neill, \{Paul M.\}",

year = "2008",

month = nov,

day = "1",

doi = "10.1016/j.bmcl.2008.09.052",

language = "English",

volume = "18",

pages = "5804--5808",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

publisher = "Elsevier Ltd",

number = "21",

}

TY - JOUR

T1 - Piperidine dispiro-1,2,4-trioxane analogues

AU - Sabbani, Sunil

AU - Stocks, Paul A.

AU - Ellis, Gemma L.

AU - Davies, Jill

AU - Hedenstrom, Erik

AU - Ward, Steve

AU - O'Neill, Paul M.

PY - 2008/11/1

Y1 - 2008/11/1

N2 - Dispiro N-Boc-protected 1,2,4-trioxane 2 was synthesised via Mo(acac)(2) catalysed perhydrolysis of N-Boc spirooxirane followed by condensation of the resulting beta-hydroperoxy alcohol 10 with 2-adamantanone. N-Boc 1,2,4-trioxane 2 was converted to the amine 1,2,4-trioxane hydrochloride salt 3 which was subsequently used to prepare derivatives (4-7). Several of these novel 1,2,4-trioxanes had nanomolar antimalarial activity versus the 3D7 strain of Plasmodium falciparum. Amine intermediate 3 represents a versatile derivative for the preparation of achiral arrays of trioxane analogues with antimalarial activity. (C) 2008 Elsevier Ltd. All rights reserved.

AB - Dispiro N-Boc-protected 1,2,4-trioxane 2 was synthesised via Mo(acac)(2) catalysed perhydrolysis of N-Boc spirooxirane followed by condensation of the resulting beta-hydroperoxy alcohol 10 with 2-adamantanone. N-Boc 1,2,4-trioxane 2 was converted to the amine 1,2,4-trioxane hydrochloride salt 3 which was subsequently used to prepare derivatives (4-7). Several of these novel 1,2,4-trioxanes had nanomolar antimalarial activity versus the 3D7 strain of Plasmodium falciparum. Amine intermediate 3 represents a versatile derivative for the preparation of achiral arrays of trioxane analogues with antimalarial activity. (C) 2008 Elsevier Ltd. All rights reserved.

KW - 1,2,4-Trioxane

KW - Antimalarial

KW - Endoperoxide

KW - Hydrogen peroxide

KW - Mechanism of action

U2 - 10.1016/j.bmcl.2008.09.052

DO - 10.1016/j.bmcl.2008.09.052

M3 - Article

SN - 0960-894X

VL - 18

SP - 5804

EP - 5808

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 21

ER -

Piperidine dispiro-1,2,4-trioxane analogues

Abstract

Keywords

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