Perchloric acid induced epimerisation of the thevinones:: an improved synthesis of 7β-dihydrothevinones

被引：6

作者：

Derrick, I ^{[1
]}

Coop, A ^{[1
]}

Al-Mousawi, SM ^{[1
]}

Husbands, SM ^{[1
]}

Lewis, JW ^{[1
]}

机构：

[1] Univ Bristol, Sch Chem, Bristol BS8 1TS, Avon, England

来源：

TETRAHEDRON LETTERS | 2000年 / 41卷 / 39期

关键词：

opioids; thevinones; 7; beta-dihydrothevinones; epimerisation;

D O I：

10.1016/S0040-4039(00)01300-9

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

The region above and away from C7 in the orvinols is known to be of particular importance in determining the mu-opioid receptor profile of this important class of opioids. However it has been difficult to explore this site due to the relative inaccessibility of 7 beta-substituted compounds. Here we report that perchloric acid induced epimerisation of the 7 alpha-ketones (dihydrothevinones) allows considerably improved access to a series of beta-ketones (beta-dihydrothevinones). The extent of epimerisation of the 7 alpha-ketone is determined by the degree of steric bulk in both the 6,14-bridge and in the ketone side chain. (C) 2000 Elsevier Science Ltd. Ail rights reserved.

引用

页码：7571 / 7576

页数：6

共 11 条

[1] NOVEL ANALGESICS AND MOLECULAR REARRANGEMENTS IN MORPHINE-THEBAINE GROUP .I. KETONES DERIVED FROM 6,14-ENDO-ETHENOTETRAHYDROTHEBAINE [J].

BENTLEY, KW ;

HARDY, DG .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1967, 89 (13) :3267-&

[2] BASE-CATALYZED REARRANGEMENTS IN THE NEPENTHONE SERIES [J].

BENTLEY, KW ;

BALL, JC .

JOURNAL OF ORGANIC CHEMISTRY, 1958, 23 (11) :1725-1730

[3] NOVEL ANALGESICS AND MOLECULAR REARRANGEMENTS IN MORPHINE-THEBAINE GROUP .12. DERIVATIVES OF 7-AMINO-6,14-ENDO-ETHENO-TETRAHYDROTHEBAINE [J].

BENTLEY, KW ;

HARDY, DG ;

SMITH, ACB .

JOURNAL OF THE CHEMICAL SOCIETY C-ORGANIC, 1969, (17) :2235-&

[4] METHYLATION OF THE ENOLATES OF THEVINONE AND SOME ANALOGS [J].

COOP, A ;

GRIVAS, K ;

HUSBANDS, S ;

LEWIS, JW .

TETRAHEDRON, 1995, 51 (35) :9681-9698

[5]

DERRICK I, UNPUB HELV CHIM ACTA

[6] NUCLEAR MAGNETIC RESONANCE STUDIES IN 6,14-ENDO-ETHENOTETRAHYDROTHEBAINE SERIES [J].

FULMOR, W ;

LANCASTER, JE ;

MORTON, GO ;

BROWN, JJ ;

HOWELL, CF ;

NORA, CT ;

HARDY, RA .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1967, 89 (13) :3322-+

[7] PROBES FOR NARCOTIC RECEPTOR MEDIATED PHENOMENA .13. POTENTIAL IRREVERSIBLE NARCOTIC ANTAGONIST-BASED LIGANDS DERIVED FROM 6,14-ENDO-ETHENOTETRAHYDROORIPAVINE WITH 7-(METHOXYFUMAROYL)AMINO, (BROMOACETYL)AMINO, OR ISOTHIOCYANATE ELECTROPHILES - CHEMISTRY, BIOCHEMISTRY, AND PHARMACOLOGYV [J].

LESSOR, RA ;

BAJWA, BS ;

RICE, KC ;

JACOBSON, AE ;

STREATY, RA ;

KLEE, WA ;

SMITH, CB ;

ACETO, MD ;

MAY, EL ;

HARRIS, LS .

JOURNAL OF MEDICINAL CHEMISTRY, 1986, 29 (11) :2136-2141

[8]

Lewis John W., 1995, P3

[9] SYNTHESIS OF N-SUBSTITUTED 7-BETA-DIPRENORPHINE DERIVATIVES [J].

MARTON, J ;

MIKLOS, S ;

HOSZTAFI, S ;

MAKLEIT, S .

SYNTHETIC COMMUNICATIONS, 1995, 25 (06) :829-848

[10] Morphine alkaloids. Part 142. Isomerization reactions of 7-substituted 6,14-bridged thebaine derivatives (Bentley compounds) [J].

Marton, J ;

Garadnay, S ;

Szabo, Z ;

Hosztafi, S ;

Makleit, S .

ACTA CHEMICA SCANDINAVICA, 1998, 52 (10) :1234-1238

← 1 2 →