A biomimetic synthesis of colchicine (1) was designed which required the intermediacy of enamine 2. The enamine was to be generated by decarboxylation or decarbonylation of the homomorphinandienone 3, formed by phenolic oxidative coupling of the phenethyltetrahydroisoquinoline 4. / (DIAGRAM, TABLE OR GRAPHIC OMITTED...PLEASE SEE DAI) / Consequently Bischler-Napieralski cyclization of N- 3-(3,4,5-trimethoxyphenyl propanoyll-3-methoxy-4-hydroxyphenyl)alanine methyl ester was employed to give a 3,4-dihydrophenethyliso- quinoline, which was reduced with sodium borohydride to form a single diastereomeric tetrahydrophenethylisoquinoline. Acylation of the latter gave the N-trifluoroacetyl derivative, which when analyzed by X-ray diffraction, was shown to be the cis isomer. Epimerization of the amine followed by acylation gave the trans isomer, which was also analyzed by X-ray diffraction. / Intramolecular phenolic oxidative coupling of cis and trans-1-(3,4,5-trimethoxyphenethyl)-2-trifluoroacetyl-3-methoxycarbonyl-6-methoxy-7-hydroxy-tetrahydroisoquinolines was investigated. It was found that oxidative coupling of the trans derivative in dry toluene using iodosobenzene bistrifluoroacetate gave the best yield of homomorphinandienone (8%). Oxidation of the cis amide under the same conditions did not result in the formation of homomorphinandienone. / In view of the low yield obtained, an alternative pathway to 2 was investigated. O-Methylandrocymbine was synthesized in 34% yield by oxidation of the amine-borane of 1-(3,4,5-trimethoxyphenethyl)-2-methyl-6-methoxy-7-hydroxy-tetrahydroisoquinoline. Oxidation of O-Methylandrocymbine with hydrogen peroxide gave a diastereomeric mixture of N-oxides, which were each subjected to a modified Polonovski reaction using acetyl chloride. It was found that anti-elimination occurred to give the enamine 2. / Reaction of enamine 2 with both cyanogen azide and diphenylphosphoryl azide resulted in rearrangement to give the amidines 5 as the only identifiable products, in addition to two unidentifiable products. None of the desired colchicine derivative 6 could be found. / (DIAGRAM, TABLE OR GRAPHIC OMITTED...PLEASE SEE DAI) / Source: Dissertation Abstracts International, Volume: 46-04, Section: B, page: 1174. / Thesis (Ph.D.)--The Florida State University, 1984.
| Identifer | oai:union.ndltd.org:fsu.edu/oai:fsu.digital.flvc.org:fsu_75568 |
| Contributors | KELLY, SHARON LYNN., Florida State University |
| Source Sets | Florida State University |
| Detected Language | English |
| Type | Text |
| Format | 135 p. |
| Rights | On campus use only. |
| Relation | Dissertation Abstracts International |
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