Oxidation of ((+OR-))-N-ethoxycarbonyl-N-norreticuline (16)* with VOCl(,3) in the presence of trifluoroacetic acid or its anion gave 69% and 78% of ((+OR-))-N-ethoxy-N-norisoboldine (18)*, respectively. / Oxidation of ((+OR-))-cis-3-methoxycarbonyl-N-methoxycarbonyl- N-norreticuline (40)* with phenyliodosodiacetate in the presence of trifluoroacetic acid gave ((+OR-))-16-methoxycarbonyl-N-methoxy- carbonyl-N-norsalutaridine (65)*, ((+OR-))-5-methoxycarbonyl-N-meth- oxycarbonyl-N-norisoboldine (77)* and ((+OR-))-N-methoxycarbonyl-7-hydroxy-6-methoxy-1-(4-methoxy-2,5-dioxocyclohex-3,6-dienyl) methyl 3-methoxycarbonyl-1,2,3,4-tetrahydroisoquinoline (80)* in yields of 25%, 20% and 9%, respectively. Oxidation of 40 with VOCl(,3) gave an 80% yield of 77*. Oxidation of 40* with thallium (III) tri- fluoroacetate gave 3% and 27% yields of 77* and 80*, respectively. / Reduction of 65* with NaBH(,4), followed by treatment with dimethylformamide dineopentyl acetal, gave a 77% yield of thebaine derivative 90*. Hydrolysis of 90* in aqueous sodium hydroxide, followed by reductive decarboxylation of the acid by photochemically induced decomposition of the derived N-hydroxy-pyridine-2-thione ester in the presence of tert-butyl thiol gave ((+OR-))-thebaine derivative 92*. The latter compound was converted to ((+OR-))-codeine upon sequential treatment with anhydrous HBr in n-butylether, aqueous sodium bicarbonate and then LiAlH(,4). / Using the same synthetic approach, (-)-(1R,3R)-40 was synthesized in 54% ee (based on HPLC analysis of its Mosher ester derivative) from optically active amino acid (R)-94*, which had been generated by asymmetric hydrogenation. Oxidation of (-)-40* with PhI(OAc)(,2) gave a 25% yield of (+)-(9R)-65* (58% ee based on HPLC analysis using a Pirkle HPLC column). Since ((+OR-))-65* had been / converted to ((+OR-))-codeine*, this work constituted a novel formal approach to the asymmetric synthesis of codeine. / *See the following pages in dissertation for illustration: 8, 23, 38, 52, 55, 62, 64 and 4. / Source: Dissertation Abstracts International, Volume: 46-11, Section: B, page: 3851. / Thesis (Ph.D.)--The Florida State University, 1985.
| Identifer | oai:union.ndltd.org:fsu.edu/oai:fsu.digital.flvc.org:fsu_75690 |
| Contributors | PHAM, PHUONG THI KIM., Florida State University |
| Source Sets | Florida State University |
| Detected Language | English |
| Type | Text |
| Format | 157 p. |
| Rights | On campus use only. |
| Relation | Dissertation Abstracts International |
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