Dichlorodicyanoquinone oxidations in the indole area. Synthesis of crenatine

Abstract

The influence of temperature on the reaction of dichlorodicyanoquinone (DDQ) with l,2,3,4-tetrahydro-/3carbolines has been explored. The DDQ oxidation of amide 2a, when performed at room temperature, gave 3a (3-acylindole)/4 (2-acylindole) in a ratio of ca. 1:1, while this was increased to 2:1 at 0 °C and to ca. 5:1 at -78 °C. This method for preparation of 4-oxo-/3-carbolines has been employed for synthesis of the /3-carboline alkaloid crenatine (11). In addition, treatment of the 4-oxotetrahydro-/3-carboline (3b) with hydrazine gave l-ethyl-4amino-/3-carboline (12) which should provide access to a series of 4-substituted /3-carbolines.

Design and Strategic Synthesis of Some β-Carboline-Based Novel Natural Products of Biological Importance

“…For the synthesis of 4-alkoxy-β-carbolines 61, Oxidation of tetrahydro-βcarbolines 57 with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ ) has also found one of the best way of synthetic method [43] (Figure 12).…”

π-Delocalized Lipophilic Cations as New Candidates for Antimalarial, Antitrypanosomal and Antileishmanial Agents: Synthesis, Evaluation of Antiprotozoal Potency, and Insight into Their Action Mechanisms

“…We accomplished the total synthesis of MVC (29a) in addition to several related β-carbolines using Cook's procedure for the synthesis of crenatine, a structurally related alkaloid, with some modifications [43][44][45] (Chart 3). The preparation of the β-carbolinium salts 30, which corresponded to the DLCs, was achieved by a simple quaternization with the alkyl tosylate or alkyl halide.…”

General Approach to the Total Synthesis of Macroline-Related Sarpagine and Ajmaline Alkaloids1

“…This oxidation completed the total synthesis of (+)-(E)16-epinormacusine B 136a, (-)-(E)16-epiaffinisine 136b and (-)-gardnerine 136c in 26%, 25% and 20% overall yields, respectively (from the respective tryptophan alkyl esters). Oxidative cyclization of 136a-c effected by DDQ in THF [54,55] The akuammidine alkaloids 139a', 139b' and 140a-c illustrated in Figure 8 contain the basic sarpagine stereochemistry and an exo-methyl ester function at C16(S), with the less stable β-axial stereochemistry. The regiospecific hydroboration (as shown in the previous section) and lactone formation between the C(6)and C(17) carbon atoms were key to the formation of the β-axial ester.…”

“…This oxidation completed the total synthesis of (+)-(E)16-epinormacusine B 136a, (-)-(E)16-epiaffinisine 136b and (-)-gardnerine 136c in 26%, 25% and 20% overall yields, respectively (from the respective tryptophan alkyl esters). Oxidative cyclization of 136a-c effected by DDQ in THF [54,55] provided the ethers 137a-c and consequently completed the first total synthesis of (+)-dehydro-16-epinormacusine 137a, (+)-dehydro-16-epiaffinisine 137b and gardnutine 137c in 25%, 24% and 18% overall yields, respectively [97]. To achieve the total synthesis of 16-epi-vellosimine 8, various oxidative conditions were attempted to provide the less stable β-axial aldehyde present in 8.…”