Synthesis and preliminary biological evaluation of β-carotene and retinoic acid oxidation products

E. M. Kithsiri Wijeratne; Manping X. Liu; Narendra B. Kantipudi; Claudia B. Brochini; A. A. Leslie Gunatilaka; Louise M. Canfield

doi:10.1016/j.bmc.2006.07.057

Synthesis and preliminary biological evaluation of β-carotene and retinoic acid oxidation products

E. M. Kithsiri Wijeratne
, Manping X. Liu
, Narendra B. Kantipudi
, Claudia B. Brochini
, A. A. Leslie Gunatilaka
, Louise M. Canfield

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

5 Scopus citations

Abstract

Synthesis of the β-carotene oxidation product, 2,3-dihydro-5,8-endoperoxy-β-apo-carotene-13-one (1) was achieved in six steps starting from β-ionone. Photo-oxygenation of all trans-retinoic acid (8) and 13-cis-retinoic acid (9) produced a mixture of 5S*,8S*-epidioxy-5,8-dihydroretinoic acid (10) and 13-cis-5S*,8S*-epidioxy-5,8-dihydroretinoic acid (11). Methylation of the crude photo-oxygenation mixture afforded the corresponding methyl esters 12 and 13, respectively, both of which underwent ready aerial oxidation yielding hitherto unknown oxidation products of retinoic acid identified as methyl 5S*,8S*-epidioxy-9,10β-epoxy-5,8,9,10-tetrahydroretinoate (14) and methyl 13-cis-5S*,8S*-epidioxy-9,10β-epoxy-5,8,9,10-tetrahydroretinoate (15). Evaluation of 1, all trans-retinoic acid (8), 13-cis-retinoic acid (9), and the photo-oxygenation products 10-15 in a panel of five cancer cell lines showed 1 to be inactive and that 11 is significantly cytotoxic compared with the other retinoic acid analogs suggesting the requirement of the carboxylic acid moiety and the cis-geometry of the 13(14) double bond for cytotoxic activity.

Original language	English (US)
Pages (from-to)	7875-7879
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry
Volume	14
Issue number	23
DOIs	https://doi.org/10.1016/j.bmc.2006.07.057
State	Published - Dec 1 2006

Keywords

DACE
Oxidation products
Retinoic acid
Synthesis
β-Carotene

ASJC Scopus subject areas

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

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10.1016/j.bmc.2006.07.057

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@article{c5cab5f5e00f48efabf9b0996618fe84,

title = "Synthesis and preliminary biological evaluation of β-carotene and retinoic acid oxidation products",

abstract = "Synthesis of the β-carotene oxidation product, 2,3-dihydro-5,8-endoperoxy-β-apo-carotene-13-one (1) was achieved in six steps starting from β-ionone. Photo-oxygenation of all trans-retinoic acid (8) and 13-cis-retinoic acid (9) produced a mixture of 5S*,8S*-epidioxy-5,8-dihydroretinoic acid (10) and 13-cis-5S*,8S*-epidioxy-5,8-dihydroretinoic acid (11). Methylation of the crude photo-oxygenation mixture afforded the corresponding methyl esters 12 and 13, respectively, both of which underwent ready aerial oxidation yielding hitherto unknown oxidation products of retinoic acid identified as methyl 5S*,8S*-epidioxy-9,10β-epoxy-5,8,9,10-tetrahydroretinoate (14) and methyl 13-cis-5S*,8S*-epidioxy-9,10β-epoxy-5,8,9,10-tetrahydroretinoate (15). Evaluation of 1, all trans-retinoic acid (8), 13-cis-retinoic acid (9), and the photo-oxygenation products 10-15 in a panel of five cancer cell lines showed 1 to be inactive and that 11 is significantly cytotoxic compared with the other retinoic acid analogs suggesting the requirement of the carboxylic acid moiety and the cis-geometry of the 13(14) double bond for cytotoxic activity.",

keywords = "DACE, Oxidation products, Retinoic acid, Synthesis, β-Carotene",

author = "\{Kithsiri Wijeratne\}, \{E. M.\} and Liu, \{Manping X.\} and Kantipudi, \{Narendra B.\} and Brochini, \{Claudia B.\} and \{Leslie Gunatilaka\}, \{A. A.\} and Canfield, \{Louise M.\}",

note = "Funding Information: Financial support from American Institute for Cancer Research (Project 01A090-REV), and College of Agriculture and Life Sciences is gratefully acknowledged. CBB thanks FAPESP (Brazil) for a Fellowship.",

year = "2006",

month = dec,

day = "1",

doi = "10.1016/j.bmc.2006.07.057",

language = "English (US)",

volume = "14",

pages = "7875--7879",

journal = "Bioorganic and Medicinal Chemistry",

issn = "0968-0896",

publisher = "Elsevier Ltd",

number = "23",

}

TY - JOUR

T1 - Synthesis and preliminary biological evaluation of β-carotene and retinoic acid oxidation products

AU - Kithsiri Wijeratne, E. M.

AU - Liu, Manping X.

AU - Kantipudi, Narendra B.

AU - Brochini, Claudia B.

AU - Leslie Gunatilaka, A. A.

AU - Canfield, Louise M.

N1 - Funding Information: Financial support from American Institute for Cancer Research (Project 01A090-REV), and College of Agriculture and Life Sciences is gratefully acknowledged. CBB thanks FAPESP (Brazil) for a Fellowship.

PY - 2006/12/1

Y1 - 2006/12/1

N2 - Synthesis of the β-carotene oxidation product, 2,3-dihydro-5,8-endoperoxy-β-apo-carotene-13-one (1) was achieved in six steps starting from β-ionone. Photo-oxygenation of all trans-retinoic acid (8) and 13-cis-retinoic acid (9) produced a mixture of 5S*,8S*-epidioxy-5,8-dihydroretinoic acid (10) and 13-cis-5S*,8S*-epidioxy-5,8-dihydroretinoic acid (11). Methylation of the crude photo-oxygenation mixture afforded the corresponding methyl esters 12 and 13, respectively, both of which underwent ready aerial oxidation yielding hitherto unknown oxidation products of retinoic acid identified as methyl 5S*,8S*-epidioxy-9,10β-epoxy-5,8,9,10-tetrahydroretinoate (14) and methyl 13-cis-5S*,8S*-epidioxy-9,10β-epoxy-5,8,9,10-tetrahydroretinoate (15). Evaluation of 1, all trans-retinoic acid (8), 13-cis-retinoic acid (9), and the photo-oxygenation products 10-15 in a panel of five cancer cell lines showed 1 to be inactive and that 11 is significantly cytotoxic compared with the other retinoic acid analogs suggesting the requirement of the carboxylic acid moiety and the cis-geometry of the 13(14) double bond for cytotoxic activity.

AB - Synthesis of the β-carotene oxidation product, 2,3-dihydro-5,8-endoperoxy-β-apo-carotene-13-one (1) was achieved in six steps starting from β-ionone. Photo-oxygenation of all trans-retinoic acid (8) and 13-cis-retinoic acid (9) produced a mixture of 5S*,8S*-epidioxy-5,8-dihydroretinoic acid (10) and 13-cis-5S*,8S*-epidioxy-5,8-dihydroretinoic acid (11). Methylation of the crude photo-oxygenation mixture afforded the corresponding methyl esters 12 and 13, respectively, both of which underwent ready aerial oxidation yielding hitherto unknown oxidation products of retinoic acid identified as methyl 5S*,8S*-epidioxy-9,10β-epoxy-5,8,9,10-tetrahydroretinoate (14) and methyl 13-cis-5S*,8S*-epidioxy-9,10β-epoxy-5,8,9,10-tetrahydroretinoate (15). Evaluation of 1, all trans-retinoic acid (8), 13-cis-retinoic acid (9), and the photo-oxygenation products 10-15 in a panel of five cancer cell lines showed 1 to be inactive and that 11 is significantly cytotoxic compared with the other retinoic acid analogs suggesting the requirement of the carboxylic acid moiety and the cis-geometry of the 13(14) double bond for cytotoxic activity.

KW - DACE

KW - Oxidation products

KW - Retinoic acid

KW - Synthesis

KW - β-Carotene

UR - https://www.scopus.com/pages/publications/33750085044

UR - https://www.scopus.com/pages/publications/33750085044#tab=citedBy

U2 - 10.1016/j.bmc.2006.07.057

DO - 10.1016/j.bmc.2006.07.057

M3 - Article

C2 - 16908162

AN - SCOPUS:33750085044

SN - 0968-0896

VL - 14

SP - 7875

EP - 7879

JO - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

IS - 23

ER -

Synthesis and preliminary biological evaluation of β-carotene and retinoic acid oxidation products

Abstract

Keywords

ASJC Scopus subject areas

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