Hedvig Bölcskei

Synthesis of vinca alkaloids and related compounds XLVIII synthesis of (+)-catharanthine and (±)-allocatharanthine☆

Abstract The first synthesis of natural (+)-catharanthine (ulbar>1) has been achieved in a few steps and in ∼20 % overall yield based on indole-3--acetic acid. The isomeric (±)-allocatharanthine was also prepared.

Synthesis of vinca alkaloids and related compounds. Part LVI. 15′,20′-Anhydrovinblastine borane complex. Structural investigations using NMR methods.

Abstract In the course of coupling catharanthine 1 to vindoline 2, the 3 borane complex of anhydrovinblastine, a new diindole derivative was isolated. The structure of this compound was studied by detailed NMR investigations. Full1H and13C assignments for both the 3 borane complex and anhydrovinblastine are given.

Synthesis of vinca alkaloids and related compounds. XLVII: Synthesis of (+)- and (-)-deethylcatharanthine

Abstract Synthesis of optically active deethylcatharanthine ( 1 ) was performed in a few steps. While studying various approaches and reaction conditions new rearrangements ( 7 → 8 → 9 and 4b → 12 ) and new heterocyclic systems (e.g. 8 , 9 , 12 , 14 ) were discovered.

Synthesis of vinca alkaloids and related compounds XVII. Synthesis of deethylcatharanthine

Abstract Starting from indolylacetic acid the synthesis of (±)deethylcatharanthine was achieved using fewer steps than the previous pathways.

A new oxidative rearrangement of vindoline

Oxidation of vindoline 1 with MnO2 yielded a rearranged product, the vincine derivative 5, among other oxidized vindoline derivatives.

Borane complexes of vinblastine type diindole derivatives

Abstract While investigating the ferric chloride mediated coupling 1 of catharanthine ( 1 ) with vindoline ( 3 ) and their derivatives ( 2,4 ), the borane complexes of 15′,20′-anhydrovinblastine 2 (AVLB), 20′-deethyl-AVLB and N-demethyl-AVLB ( 9,10,11 ) have been synthesized. The corresponding bases ( 6,7 and 8 ) have also been obtained in high yield.

Synthesis of vinca alkaloids and related compounds, Part XCVI [1] Nitration study of vinblastine‐type bisindole alkaloids

The bisindole alkaloids vinblastine, vincristine, and N‐formyl‐leurosine were nitrated and subsequently converted to amino derivatives. In the case of compounds 5e and 5b cytotoxic activity has been found for non‐small cell lung cancer and breast cancer in the concentration range tested (10−5 — 10−9 M). 5b also showed potency in the screen for colon cancer and leukemia.

Biomimetic synthesis and HPLC-ECD analysis of the isomers of dracocephins A and B

Starting from racemic naringenin ((±)-1), a mixture of dracocephin A stereoisomers 6-(2”-pyrrolidinone-5”-yl)naringenin (±)-2a–d and its regioisomer, dracocephin B 8-(2”-pyrrolidinone-5”-yl)naringenin (±)-3a–d originally isolated from Dracocephalum rupestre, have been synthesized in a one-pot reaction. The separation of 2a–d and 3a–d was achieved by preparative HPLC. The four stereoisomers of each natural product were separated by analytical chiral HPLC and their absolute configuration was studied by the combination of HPLC–ECD measurements and TDDFT–ECD calculations. The synthesized flavonoid alkaloids were further characterized by physicochemical and in vitro pharmacological studies.

Azabicyclo[3.2.1]octene derivatives obtained by rearrangement reactions in course of the catharanthine synthesis

In the course of our synthesis of the alkaloid catharanthine l a (2+4+6+1)273, allocatharanthine l b and deethylcatharanthine lc, several azabicyclo [3.2. lloctene derivatives were obtained by rearrangement of the isoquinuclidine ring system. The structures and stereochemistry of the azabicyclo[3.2. lloctene derivatives were determined by various NMR methods (NOE and two-dimensonal INEPT experiments). On coupling of the alkaloid catharantine l a with vindoline antitumor vinblastine derivatives can be obtained1 . The main synthetic route293 of 1 (2-+4+6+1) (Figure 1) was accompanied by rearrangement reactions of the azabicyclo[2.2.2]octene skeleton4. To avoid the unwanted rearrangement we .tried to protect the nitrogen of the isoquinuclidine by acylation. Starting from 2 a simple acylation with indolyl-acetic acid pivalic acid mixed anhydride @MF, rt.) took place in good yield. On the other hand derivative 3 having the chlorine atom in endo position proved to be unstable under similar conditions.

Synthesis of Vinca Alkaloids and Related Compounds. Part LXX1. Ferric Chloride Mediated Coupling Reaction of Rearranged 5-nor-catharanthine with Vindoline

Abstract While investigating the ring opening-closure process of the C ring of catharanthine (2), a new type of dimer (5) and two rearranged “monomeric” compounds (3,4) have been obtained. In the course of the coupling process of the rearranged iboga-skeleton monomer (3) with vindoline (6) in the presence of ferric chloride in aqueous media three dimer compounds (7,8 and 9) have been produced.