Synthesis of Tropine-labeled Atropine I. Micro-methods for the Synthesis of Tropine and for its Esterification with Tropic Acid
Gilbert C. Schmidt, Thomas E. Eling, John C. Drach
J. Pharm. Sci.
Vol.56(2) 1967 pp.215-221
DOI: 10.1002/jps.2600560213
Abstract
Yields for each step in the esterification of tropine and tropic acid have been determined with micro and semimicro quantities of reactants. In a similar way, the Robinson condensation has been studied. Data are compared with the findings of other investigators. In the esterification of micro quantities of tropine and tropic acid, 70–75 per cent of theoretical atropine yields are obtained routinely. Based on any intermediate in the Robinson condensation, micro quantities of reactants routinely produce 67–72 per cent of theoretical tropine yields. Predicted yields of 47–54 per cent atropine from Robinson intermediates were confirmed by synthesis of atropine from each of the Robinson reactants. The procedures are designed for the synthesis of labeled tropine and tropine-labeled atropine from labeled arabinose.
Synthesis of Tropine-labeled Atropine II. Prototype Synthesis for the Preparation of Tropine-14C and Aropine-14C from Arabinose-14C
Gilbert C. Schmidt, Thomas E. Eling, John M. McOwen, John C. Drach
J. Pharm. Sci.
Vol.56(11) 1967 pp.1453-1459
DOI: 10.1002/jps.2600561116
Abstract
Prototype methods for the synthesis of tropines-14C and tropine-labeled atropines are described. These compounds and the requisite labeled intermediates may be synthesized from arabinose-5-14C or arabinose-UL-14C. Yields for each step in the conversion of arabinose to succindialdehyde via 2, 5-diethoxytetrahydrofuran have been determined. Predicted yields of 27 per cent atropine, based on starting pentose, were confirmed by synthesis of the alkaloid from 2 mmole quantities of arabinose. This procedure is the first published method for labeling atropine in the carbon skeleton of the tropine moiety.
Synthesis of Tropine-labeled Atropine III. Synthesis of N-methyl-14C-tropine and N-methyl-14C-atropine
Gilbert C. Schmidt, Thomas E. Eling, John M. McOwen
J. Pharm. Sci.
Vol.57(3) 1968 pp.443-446
DOI: 10.1002/jps.2600570315
Abstract
Using a previously described modification of the Robinson condensation, N-methyl-14C-tropine, specific gravity 1 mc./mmole, was synthesized from methylamine-14C-HCl in 65 percent of theoretical yield. Subsequent esterification with unlabeled tropic acid gave N-methyl-14C-atropine, specific activity 1 mc./mmole, in 45 percent of theoretical yield, based on methylamine. Synthesis of these compounds validates previous studies and firmly establishes a general pathway for labeling the carbon skeleton of tropine with radioactive carbon.
Synthesis of Tropine-labeled Atropine IV. Labeling of the 2, 3, and 4 Positions of Atropine from Citric-14C acid
Thomas E. Eling, John M. McOwen, Gilbert C. Schmidt
J. Pharm. Sci.
Vol.57(
1968 pp.1357-1360
DOI: 10.1002/jps.2600570817
Abstract
Using a modification of the Robinson condensation, citric-3-14C acid, citric-2,4-14C acid, and citric-2,3,4-14C acid were converted into correspondingly labeled tropine and atropine. The specific activities of the products varied from 0.62 to 1.0 depending on the labeled compound. This is the first reported syntheses of tropine or atropine labeled with 14C in positions other than the endo-methyl group.
Gilbert C. Schmidt, Thomas E. Eling, John C. Drach
J. Pharm. Sci.
Vol.56(2) 1967 pp.215-221
DOI: 10.1002/jps.2600560213
Abstract
Yields for each step in the esterification of tropine and tropic acid have been determined with micro and semimicro quantities of reactants. In a similar way, the Robinson condensation has been studied. Data are compared with the findings of other investigators. In the esterification of micro quantities of tropine and tropic acid, 70–75 per cent of theoretical atropine yields are obtained routinely. Based on any intermediate in the Robinson condensation, micro quantities of reactants routinely produce 67–72 per cent of theoretical tropine yields. Predicted yields of 47–54 per cent atropine from Robinson intermediates were confirmed by synthesis of atropine from each of the Robinson reactants. The procedures are designed for the synthesis of labeled tropine and tropine-labeled atropine from labeled arabinose.
Synthesis of Tropine-labeled Atropine II. Prototype Synthesis for the Preparation of Tropine-14C and Aropine-14C from Arabinose-14C
Gilbert C. Schmidt, Thomas E. Eling, John M. McOwen, John C. Drach
J. Pharm. Sci.
Vol.56(11) 1967 pp.1453-1459
DOI: 10.1002/jps.2600561116
Abstract
Prototype methods for the synthesis of tropines-14C and tropine-labeled atropines are described. These compounds and the requisite labeled intermediates may be synthesized from arabinose-5-14C or arabinose-UL-14C. Yields for each step in the conversion of arabinose to succindialdehyde via 2, 5-diethoxytetrahydrofuran have been determined. Predicted yields of 27 per cent atropine, based on starting pentose, were confirmed by synthesis of the alkaloid from 2 mmole quantities of arabinose. This procedure is the first published method for labeling atropine in the carbon skeleton of the tropine moiety.
Synthesis of Tropine-labeled Atropine III. Synthesis of N-methyl-14C-tropine and N-methyl-14C-atropine
Gilbert C. Schmidt, Thomas E. Eling, John M. McOwen
J. Pharm. Sci.
Vol.57(3) 1968 pp.443-446
DOI: 10.1002/jps.2600570315
Abstract
Using a previously described modification of the Robinson condensation, N-methyl-14C-tropine, specific gravity 1 mc./mmole, was synthesized from methylamine-14C-HCl in 65 percent of theoretical yield. Subsequent esterification with unlabeled tropic acid gave N-methyl-14C-atropine, specific activity 1 mc./mmole, in 45 percent of theoretical yield, based on methylamine. Synthesis of these compounds validates previous studies and firmly establishes a general pathway for labeling the carbon skeleton of tropine with radioactive carbon.
Synthesis of Tropine-labeled Atropine IV. Labeling of the 2, 3, and 4 Positions of Atropine from Citric-14C acid
Thomas E. Eling, John M. McOwen, Gilbert C. Schmidt
J. Pharm. Sci.
Vol.57(
1968 pp.1357-1360DOI: 10.1002/jps.2600570817
Abstract
Using a modification of the Robinson condensation, citric-3-14C acid, citric-2,4-14C acid, and citric-2,3,4-14C acid were converted into correspondingly labeled tropine and atropine. The specific activities of the products varied from 0.62 to 1.0 depending on the labeled compound. This is the first reported syntheses of tropine or atropine labeled with 14C in positions other than the endo-methyl group.
I.Micro.Methods.for.the.Synthesis.of.Atropine.and.its.Esterification.with.Tropic.Acid.pdf