Pirjo Hanhinen

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 .

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.

Claisen Orthoester Rearrangement in the Direct Preparation of Z-Isositsirikine and Z-Geissoschizine Derivatives Possessing the Right Oxidation State at C-17

Abstract The Claisen orthoester rearrangement utilizing allylic alcohol 1 (or 2 ) and trimethyl 3-methoxyortbopropionate 13a leads to Z-isositsirikine derivatives 21a–22a (or 23a–24a ) possessing one RO-function at C-17. In the cases of trialkyl 3,3-dialkoxyorthopropionates [triethyl 3,3-diethoxyorthopropionate 14b (or 3,3-diethoxymethylketene diethylacetal 20b ) and trimethyl 3,3-dimethoxyorthopropionate 14 a (or 3,3-dimethoxymethylketene dimethylacetal 20a )], the intermediate ketene acetals 25a,b do not rearrange according to the Claisen mechanism to form compounds 26a,b and/or 27a,b possessing two RO-functions at C-17. Syntheses of the intermediate orthoesters, trimethyl 3-methoxyorthopropionate 13a , trimethyl 3,3-dimethoxyorthopropionate 14a , trimethyl trans -3-methoxyorthoacrylate 20c , and triethyl 3,3-diethoxyorthopropionate 14b are described.

Studies on the biomimetic preparation of the sarpagan ring system. Attempts to apply the spontaneous “biogenetic-type cyclization” of van Tamelen to bond formation between C-5 and C-16 in the corynantheine series

Abstract Attempts were made to apply the spontaneous “biogenetic-type cyclization” of van Tamelen to the preparation of the sarpagan ring system by utilizing indolo [2,3-a]quinolizidines 10, 11, 12, and 14 . The fact that the spontaneous “biogenetic-type cyclization” did not take place casts some doubt on the correctness of the earlier results.

Preparation and conformational study of Z-isositsirikine model compounds and their cis-Nb-oxides. Determination of the C-16 configuration

Preparation of Z-isositsirikine derivatives (5-12) from the allylic alcohols (21) and (22) by the orthoester Claisen rearrangement and their oxidation to the corresponding cis-N b -oxides (13-20) are described. Nmr methods were applied to determine the configuration at C-16 of Z-isositsirikine derivatives and their cis-N b -oxides. A general, nmr based conformational study of compounds (5-20) is presented

Short, Stereospecific Total Synthesis of (+-)-Corynantheidine

Abstract A short, stereospecfic total synthesis of indole alkaloid (±)-corynantheidine 1 is described.

The ajmaline group of indole alkaloids.

Publisher Summary This chapter discusses an area of indole alkaloids, which has been neglected in the series for over 30 years—namely, the ajmaline group of alkaloids, where numerous advances in chemistry and biosynthesis have been made recently. The number of known ajmaline structures has grown markedly in recent years to a present count of 77. Some of these might be artefacts and a few structures have not been convincingly determined. In addition, seven bisindole alkaloids containing at least one monomeric ajmalan unit have been isolated, increasing the total number to 84. Ajmaline alkaloids contain the polycyclic ajmalan ring system. The “biogenetic numbering” of Le Men and Taylor is used throughout the chapter. The priority sequence for the C-17 substituents in the Cahn–Ingold–Prelog system is different in the absence and presence of the COOCH, substituent at C-16. All of the ajmaline alkaloids found thus far occur in the plant family Apocynaceae. They have been recognized in the following genera Alstonia , Aspidospenna , Cabucala , Melodinus , Rauvolfia , Tonduzia (Alstonia), and Vinca .

Preparation and determination of stereochemical properties of epimeric z-geissoschizine and 19,20-dihydrogeissoschizine acetals

Abstract Preparation and determination of stereochemical properties of epimeric Z-geissoschizine and 19,20-dihydrogeissoschizine acetals arc described. The determination of the stereochemical properties is mainly based on nmr measurements.