Process for producing L-ambrox
AssigneeKuraray Co., Ltd.
InventorsGoro Asanuma, Yoshin Tamai
Life of this patent
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Abstract
(-)-2,5,5,8a-Tetramethyl-1-(carboxymethyl)-2-hydroxydecalin is subjected to lactonization by dehydration to form decahydro-3a,6,6,9a-tetramethyl(3a.alpha.,5a.beta.,9a.alpha.,9b.beta.)-(+) -naphtho[2,1-b]furan-2(1H)-one, which is then reduced with a metal hydride to convert it into (-)-2,5,5,8a-tetramethyl-1-(carboxymethyl)-2-hydroxydecalin, followed by dehydrative cyclization to give L-ambrox. The (-)-2,5,5,8a-tetramethyl-1-(carboxymethyl)-2-hydroxydecalin is produced from its racemic mixture. The resolution is performed using a 1-(aryl)ethylamine. The starting material for the synthesis is beta-ionone.
Claims4
A process for producing (-)-3a,6,6,9a-tetramethyl-dodecahydronaphtho[2,1-b]furan, comprising the steps of:
- allowing (.+-.)-2,5,5,8a-tetramethyl-1-(carboxymethyl)-2-hydroxydecalin to react with an optically resolving agent comprising an optically active 1-(aryl)ethylamine to form two kinds of diastereomer salts, and optically resolving from said diastereomer salts a salt comprised of (-)-2,5,5,8a-tetramethyl-1-(carboxymethyl)-2-hydroxydecalin and the optically active 1-(aryl)ethylamine, followed by hydrolysis to give (-)-2,5,5,8a-tetramethyl-1-(carboxymethyl)-2-hydroxydecalin;
- subjecting said (-)-2,5,5,8a-tetramethyl-1-(carboxymethyl)-2-hydroxydecalin to lactonization by dehydration to form decahydro-3a,6,6,9a-tetramethyl-(3a.alpha.,5a.beta.,9a.alpha.,9b.beta.)-(+ )-naphtho[2,1-b]furan-2(1H)-one;
- reducing the lactonized compound to convert it into (-)-2,5,5,8a-tetramethyl-1-(carboxymethyl)-2-hydroxydecalin;
- and
- subjecting the reduced compound to dehydrative cyclization to give (-)-3a,6,6,9a-tetramethyl-dodecahydronaphtho[2,1-b]furan.
A process for producing (-)-3a,6,6,9a-tetramethyl-dodecahydronaphtho[2,1-b]furan, comprising the steps of:
- allowing a carbonate of dihydro-.beta.-vinyl-ionol to react with carbon monoxide in the presence of a palladium catalyst to form .beta.-monocyclohomofarnesic acid;
- cyclizing said .beta.-monocyclohomofarnesic acid in the presence of an acid catalyst to form (.+-.)-norambreinolide, hydrolyzing said (.+-.)-norambreinolide to form (.+-.)-2,5,5,8a-tetramethyl-1-(carboxymethyl)-2-hydroxydecalin;
- allowing said (.+-.)-2,5,5,8a-tetramethyl-1-(carboxymethyl)-2-hydroxydecalin to react with an optically resolving agent comprising an optically active 1-(aryl)ethylamine to form two kinds of diastereomer salts, and optically resolving from said diastereomer salts a salt comprised of (-)-2,5,5,8a-tetramethyl-1-(carboxymethyl)-2-hydroxydecalin and the optically active 1-(aryl)ethylamine, followed by hydrolysis to give (-)-2,5,5,8a-tetramethyl-1-(carboxymethyl)-2-hydroxydecalin;
- subjecting said (1)-2,5,5,8a-tetramethyl-1-(carboxymethyl)-2-hydroxydecalin to lactonization by dehydration to form decahydro-3a,6,6,9a-tetramethyl-(3a.alpha.,5a.beta.,9a.alpha.,9b.beta.)-(+ )-naphtho[2,1-b]furan-2(1H)-one;
- reducing the lactonized compound to convert it into (-)-2,5,5,8a-tetramethyl-1-(carboxymethyl)-2-hydroxydecalin;
- and
- subjecting the reduced compound to dehydrative cyclization to give (-)-3a,6,6,9a-tetramethyl-dodecahydronaphtho[2,1-b]furan.
A process for optically resolving (.+-.)-2,5,5,8a-tetramethyl-1-(carboxymethyl)-2-hydroxydecalin into optically active (-)-form and (+)-form thereof, wherein said (.+-.)-2,5,5,8a-tetramethyl-1-(carboxymethyl)-2-hydroxydecalin is allowed to react with an optically resolving agent comprising an optically active 1-(aryl)ethylamine, to form a diastereomer.
Dependencies are inferred from the claim text.