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Title: Design, synthesis, and evaluation of omega-iodovinyl- and omega-iodoalkyl-substituted methyl-branched long-chain fatty acids

Abstract

The synthesis of a new methyl-branched fatty acid, (E)-19-iodo-3(RS)-methyl-18-nonadecenoic acid (19), is described. Methyl branching has been introduced at the 3-position to inhibit beta-oxidation and radioiodide has been attached as a trans-vinyl iodide. Preparation of 19 involved a 15-step sequence of reactions climaxing with formation of the methyl ester 18 by iododestannylation of methyl (E)-19-(tri-n-butylstannyl)-3(RS)-methyl-18-nonadecenoate (17) resulting from the reaction of n-Bu3SnH with methyl 3(RS)-methyl-18-nonadecynoate (16). Methyl branching was introduced at an early stage by Friedel-Crafts acylation of thiophene with 3(RS)-methyl-4-carbomethoxybutanoyl chloride (3) generated from 3-methylglutaric anhydride. The new agent, (/sup 125/I)-19, showed high myocardial uptake (5 min, 4.89% dose/g; 30 min, 3.32% dose/g), good heart/blood (H/B) ratios (5 min, 5.4/1; 30 min, 4.3/1), and significantly greater myocardial retention in fasted rats than the corresponding straight-chain analogue 19-(/sup 125/I)-iodo-18-nonadecenoic acid (5 min, 3.52% dose/g, H/B = 4.8/1; 30 min, 1.19% dose/g, H/B = 1.6/1). Excellent myocardial images were obtained in rats after administration of (123I)-19 and confirmed the slow myocardial washout over a 60-min period. These data suggest that 19 is a good candidate for evaluation of heart disease involving aberrations in fatty acid metabolism by use of imaging techniques such as single photon emission computerized tomography (SPECT) where redistributionmore » or washout should be minimized.« less

Authors:
; ;
Publication Date:
Research Org.:
Oak Ridge National Lab., TN
OSTI Identifier:
5253758
Resource Type:
Journal Article
Journal Name:
J. Med. Chem.; (United States)
Additional Journal Information:
Journal Volume: 6
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; CARBOXYLIC ACIDS; BIOSYNTHESIS; TISSUE DISTRIBUTION; HYPERTENSION; IODINE 125; METABOLISM; MYOCARDIUM; RATS; RETENTION; SINGLE PHOTON EMISSION COMPUTED TOMOGRAPHY; ANIMALS; BETA DECAY RADIOISOTOPES; BODY; CARDIOVASCULAR DISEASES; CARDIOVASCULAR SYSTEM; COMPUTERIZED TOMOGRAPHY; DAYS LIVING RADIOISOTOPES; DIAGNOSTIC TECHNIQUES; DISEASES; DISTRIBUTION; ELECTRON CAPTURE RADIOISOTOPES; EMISSION COMPUTED TOMOGRAPHY; HEART; INTERMEDIATE MASS NUCLEI; IODINE ISOTOPES; ISOTOPES; MAMMALS; MUSCLES; NUCLEI; ODD-EVEN NUCLEI; ORGANIC ACIDS; ORGANIC COMPOUNDS; ORGANS; RADIOISOTOPES; RODENTS; SYMPTOMS; SYNTHESIS; TOMOGRAPHY; VASCULAR DISEASES; VERTEBRATES; 550201* - Biochemistry- Tracer Techniques

Citation Formats

Goodman, M M, Callahan, A P, and Knapp, Jr, F F. Design, synthesis, and evaluation of omega-iodovinyl- and omega-iodoalkyl-substituted methyl-branched long-chain fatty acids. United States: N. p., 1985. Web. doi:10.1021/jm00383a020.
Goodman, M M, Callahan, A P, & Knapp, Jr, F F. Design, synthesis, and evaluation of omega-iodovinyl- and omega-iodoalkyl-substituted methyl-branched long-chain fatty acids. United States. https://doi.org/10.1021/jm00383a020
Goodman, M M, Callahan, A P, and Knapp, Jr, F F. 1985. "Design, synthesis, and evaluation of omega-iodovinyl- and omega-iodoalkyl-substituted methyl-branched long-chain fatty acids". United States. https://doi.org/10.1021/jm00383a020.
@article{osti_5253758,
title = {Design, synthesis, and evaluation of omega-iodovinyl- and omega-iodoalkyl-substituted methyl-branched long-chain fatty acids},
author = {Goodman, M M and Callahan, A P and Knapp, Jr, F F},
abstractNote = {The synthesis of a new methyl-branched fatty acid, (E)-19-iodo-3(RS)-methyl-18-nonadecenoic acid (19), is described. Methyl branching has been introduced at the 3-position to inhibit beta-oxidation and radioiodide has been attached as a trans-vinyl iodide. Preparation of 19 involved a 15-step sequence of reactions climaxing with formation of the methyl ester 18 by iododestannylation of methyl (E)-19-(tri-n-butylstannyl)-3(RS)-methyl-18-nonadecenoate (17) resulting from the reaction of n-Bu3SnH with methyl 3(RS)-methyl-18-nonadecynoate (16). Methyl branching was introduced at an early stage by Friedel-Crafts acylation of thiophene with 3(RS)-methyl-4-carbomethoxybutanoyl chloride (3) generated from 3-methylglutaric anhydride. The new agent, (/sup 125/I)-19, showed high myocardial uptake (5 min, 4.89% dose/g; 30 min, 3.32% dose/g), good heart/blood (H/B) ratios (5 min, 5.4/1; 30 min, 4.3/1), and significantly greater myocardial retention in fasted rats than the corresponding straight-chain analogue 19-(/sup 125/I)-iodo-18-nonadecenoic acid (5 min, 3.52% dose/g, H/B = 4.8/1; 30 min, 1.19% dose/g, H/B = 1.6/1). Excellent myocardial images were obtained in rats after administration of (123I)-19 and confirmed the slow myocardial washout over a 60-min period. These data suggest that 19 is a good candidate for evaluation of heart disease involving aberrations in fatty acid metabolism by use of imaging techniques such as single photon emission computerized tomography (SPECT) where redistribution or washout should be minimized.},
doi = {10.1021/jm00383a020},
url = {https://www.osti.gov/biblio/5253758}, journal = {J. Med. Chem.; (United States)},
number = ,
volume = 6,
place = {United States},
year = {Sat Jun 01 00:00:00 EDT 1985},
month = {Sat Jun 01 00:00:00 EDT 1985}
}