SYNTHESIS OF PHOSPHONIC AND PHOSPHINIC ACID ANALOGUES OF OLIGONUCLEOTIDES AND CHOLESTEROL INHIBITORS.
Item
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Title
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SYNTHESIS OF PHOSPHONIC AND PHOSPHINIC ACID ANALOGUES OF OLIGONUCLEOTIDES AND CHOLESTEROL INHIBITORS.
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Identifier
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AAI8302561
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identifier
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8302561
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Creator
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GOTLINSKY, BARRY.
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Contributor
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Robert Engel
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Date
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1982
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Language
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English
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Publisher
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City University of New York.
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Subject
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Chemistry, Organic
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Abstract
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The present thesis encompasses two separate projects. The first project described is a synthetic procedure for the preparation of a phosphinic acid analogue of a sequenced trinucleotide. The synthesis has a relatively simple starting material, D-glucose, which, through the series of reactions is developed to the oligonucleotide analogue. This analogue, having no hydrolyzable phosphate ester oxygen, is seen as being valuable for further understanding of details of protein synthesis.;The synthesis involves linking three carbohydrate ring systems via a pair of Wittig reactions, with the nucleoside base added prior to each coupling. Each ring system must also be functionalized specifically. After obtaining the trinucleotide system, the protecting groups are removed to yield the desired product.;The second project involves the synthesis of the phosphonic acid analogue of phosphomevalonate, an important intermediate in the biosynthesis of cholesterol and its linkage to a bile acid related material. After being coupled to a bile acid derivative, the phosphomevalonate analogue is capable of being carried to the liver where it may inhibit cholesterol biosynthesis. This was confirmed by studies using a carbon-14 label in the analogue.;A series of phosphates were also synthesized and linked to the bile acid derivative for biological control experiments. The same reagents were used to accomplish the esterification as for the previously noted coupling.
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
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Program
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Chemistry
