Reija Jokela

Syntheses of (±)-Z-Geissoschizol, (±)-3-epi-Z-Geissoschizol, (±)-Corynantheidol, (±)-Dihydrocorynantheol, (±)-3-epi-Dihydrocorynantheol and the Corresponding Corynan-17-oic Acid Methyl Esters

The utility of the Claisen rearrangement using carefully separated, diastereoisomeric allylic alcohols (1a) and (1b) in the preparation of (±)-Z-geissoschizol (4a), (±)-3-epi-Z-geissoschizol (4b), (±)-corynantheidol (7a), (±)-dihydrocorynantheol (8a), (±)-3-epi-dihydrocorynantheol (8b) and the corresponding corynan-17-oic acid methyl esters (3a, 3b, 5a, 6a and 6b) is shown. Special attention is paid to the stereochemical outcome of catalytic (PtO 2 ) hydrogenation of the C(20) Z-ethylidene side chain

Preparation and conformational study of Z- and E-Isositsirikine epimers and model compounds. Determination of their C-16 configurations

Abstract Syntheses are reported for isositsirikine isomers 1 – 6 and (16S*)-and (16R*)-17-deoxy- E -isositsirikines 9 and 10 (Model compounds 1,2 for the “synthetically missing” (16R)- and (16S)- E -isositsirikines 7 and 8 , respectively). Predominant conformations of the compounds, and of their C-16 configurations were determined on the basis of nmr measurements, especially NOE difference spectroscopy. The large difference in chemical shifts (δ 4.31 ppm versus δ 3.9 ppm), between the C-3-H-signals of (16R)- and (16S)- E -isositsirikines 7 and 8 is explained. The 13 C-nmr data confirm the non-identity of compounds 1 – 6 with rhazimanine and bhimberine, alkaloids isolated from Rhazya stricta .

Indoloquinolizidine iminium species formed under the modified Polonovski reaction conditions

Abstract The regioselectivity in the formation of different iminium species, generated from four indoloquinolizidines under the modified Polonovski reaction conditions, was studied using NaBD4-reduction and cyanide trapping of the intermediate iminium ions.

Stereoregulation of the C(12b)H-C(2)H relationship in the preparation of 2-substituted 1,2,3,4,6,7,12,12b-octahydro-indolo[2,3-a]quinolizines

Abstract Stereochemical control in the preparation of 2-substituted1,2,3,4,6,7,12,12b-octahydroindolo[2,3- a ]quinolizinespossessing at will the C(12b)H-C(2)H cis or trans configuration was achieved by catalytic reduction of the 2,3-dehydro analoques,which were either unsubstituted on the indole nitrogen orsubstituted with a BOC-group, respectively. The contribution ofdifferent conformations to the conformational equilibrium of theprepared compounds was estimated by 13C NMR spectral analysis.

Short synthesis of (+-)-hirsutine: direct addition of dimethyl malonate anion to a 1,4-conjugate iminium salt of appropriate 3-ethylindolo[2,3-a]quinolizidine

Abstract Direct addition of dimethyl malonate anion to a 1,4-conjugate iminium salt of 3-ethylindolo[2,3- a ]quinolizidine 4a (regenerated from the corresponding α-aminonitrile 4b ) afforded enamine 5. Catalytic hydrogenation of compound 5 led stereoselectively to compound 6 ( pseudo ), which is the highly desired intermediate for the preparation of several Corynanthe alkaloids, including (±)-hirsutine 7.

Novel applications of the modified Polonovski reaction. IX: A new route to Wenkert's enamine

Abstract A practical synthetic entry to Wenkerts enamine 1 employing the modified Polonovski reaction is described. Complete 13C NMR spectral data of 1 is presented. Conformational analysis of the intermediate 1-hydroxy- and 1-ethyl-1-hydroxy-indoloquinolizidines 20a , 20b , 21a and 21b based on simple but reliable 13C NMR spectral correlations is presented.

Synthetic studies in the alkaloid field—VII1: Stereochemistry of 1,2,3,4,6,7,12,12b-octahydroindolo [2,3-a]quinolizine derivatives prepared by alkaline decarboalkoxylative cyclization or acid-induced cyclization of appropriate tetrahydropyridines

Abstract The C(12b)-C(1)-C(2) stereochemical relationship in several racemic 1,2,3,4,6,7,12,12b-octahydroindolo [2,3-a]quinolizine derivatives has been determined by 13C NMR spectral analysis. The proper shift assignment was confirmed by recording the spectra of selectively deuterated derivatives. The C(12b)-C(1)-C(2) stereochemical relationship in indolo[2,3-a]quinolizines obtained either by alkaline decarboalkoxylative cyclization or by acid-induced cyclization of partially hydrogenated 1-[2-(3-indolyl)ethyl]-3-methoxycarbonylpyridine derivatives is discussed. The ambiguity existing in the preparation of dl-18,19-dihydroantirhine 2 by analogous decarboalkoxylative cyclization is considered.

The Claisen Rearrangement in the Preparation of Geissoschizine Isomers

Abstract The Claisen rearrangement of vinyl allyl ether 3 in refluxing toluene leads to a mixture of (±)- Z -geissoschizine 5 and (±)-15-epi- E -geissoschizine 6 [= (±)-3-epi- E -geissoschizine 6′], whereas vinyl allyl ether 4, under the same reaction conditions, affords only (±)-15-epi- Z -geissoschizine 15 [= (±)-3-epi- Z -geissoschizine 15′]. No (±)- E -geissoschizine 16 was formed. However, the formation of (±)-15-epi- E -geissoschizine 6 [ = (±)-3-epi- E -geissoschizine 6′], which has earlier been transformed to (±)- E -geissoschizine 16, represents a new, formal total synthesis of (±)- E -geissoschizine 16. A conformational study of the prepared compounds, mainly based on nmr measurements, is presented.

Synthesis of compounds in the eburnamonine-homoeburnamonine series

Abstract Six different lactams of the desethyleburnamonine-homoeburnamonine series were synthesized. Complete 13 C NMR data are presented for these compounds, as well as for their precursors. Special attention is paid to their C(20)–C(21) stereochemistry.

Binding of strychnocarpine and related β-carbolines to brain receptors in vitro

Abstract The affinity of strychnocarpine and related β-carbolines for serotonin, benzodiazepine, tryptamine, opiate and GABA receptors in rat brain was studied. Strychnocarpine showed a low to very low affinity for all the receptors tested. The weak binding to tryptamine receptors might explain part of the tremorigenic effects found earlier in the in vivo studies.