Tomasz Janosik

Synthetic Studies of Cephalandole Alkaloids and the Revised Structure of Cephalandole A

A synthesis of the originally proposed 2-(1 H-indol-3-yl)-4 H-3,1-benzoxazin-4-one structure of the alkaloid cephalandole A (1) led to a structural revision, and the isolated natural product has now been identified as the previously known compound 3-(1 H-indol-3-yl)-2 H-1,4-benzoxazin-2-one (7). The structural assignment was corroborated by detailed NMR studies. A short synthesis of the related natural compound cephalandole B (2) has also been performed, confirming its structure. In addition some chemical transformations, involving, for example, the related synthetic molecule 2-(1 H-indol-3-yl)-3 H-quinazolin-4-one (9), are presented.

Reactions of 2,3′-biindolyl: Synthesis of indolo[3,2-a]carbazoles

2,3′-biindolyl (9) has been transformed into indolo[3,2-a]carbazoles 16a-b by means of formal [4 + 2] cycloadditions with co-formation of the Michael adducts 17a-b. The parent indolo[3,2-a]carbazole (6) has been prepared in one step from 9 in excellent yield. Several 3-substituted 2,3′-biindolyls have also been prepared in good yields and underwent further transformations, demonstrating the versatility of 2,3′-biindolyl (9) as a building block for synthesis of indolo[3,2-a]carbazoles.

Synthesis of the marine alkaloids rhopaladins A, B, C and D

The total synthesis of all four known rhopaladins, A-D, isolated from the Okinawan marine tunicate Rhopalaea sp., in two synthetic steps is described, involving an imidate based cyclization with tryptophan esters as the key step to afford the appropriately substituted imidazolinone unit. A short and efficient new synthesis of indol-3-yl-carbonyl nitriles from indol-3-yl-carboxaldehydes and trimethylsilyl cyanide, followed by oxidation with DDQ is also described.

Reactions of 1 ,2-Bis(1H-indol-2-yl)ethane: Formation of indolo(2,3-c)carbazole and cyclohept(1,2-b :5,4-b')bisindole derivatives

1,2-Bis(1H-indol-2-yl)ethane (9) has been prepared and converted into indolo[2,3-c]carbazole (8) using palladium acetate in refluxing acetic acid. Reaction of 9 with CoF3 in hot TFA led to isolatio ...

Synthesis and bioanalytical evaluation of morphine-3-O-sulfate and morphine-6-O-sulfate in human urine and plasma using LC-MS/MS

The aim of this work was to synthesize morphine-3-O-sulfate and morphine-6-O-sulfate for use as reference substances, and to determine the sulfate conjugates as possible heroin and morphine metabolites in plasma and urine by a validated LC-MS/MS method. Morphine-6-O-sulfate and morphine-3-O-sulfate were prepared as dihydrates from morphine hydrochloride, in overall yields of 41 and 39% with product purities of >99.5% and >98%, respectively. For bioanalysis, the chromatographic system consisted of a reversed-phase column and gradient elution. The tandem mass spectrometer was operated in the positive electrospray mode using selected reaction monitoring, of transition m/z 366.15 to 286.40. The measuring range was 5-500 ng/mL for morphine-3-O-sulfate and 4.5-454 ng/mL for morphine-6-O-sulfate in plasma. In urine, the measuring range was 50-5000 ng/mL for morphine-3-O-sulfate and 45.4-4544 ng/mL for morphine-6-O-sulfate. The intra-assay and total imprecision (coefficient of variation) was below 11% for both analytes in urine and plasma. Quantifiable levels of morphine-3-O-sulfate in authentic urine and plasma samples were found. Only one authentic urine sample contained a detectable level of morphine-6-O-sulfate, while no detectable morphine-6-O-sulfate was found in plasma samples.

Chapter 5.2 - Five-membered ring systems: pyrroles and benzo derivatives

This chapter discusses the progress in synthesis and chemistry of pyrroles, indoles, and related fused ring systems. Several specialized reviews on the chemistry of indoles and pyrroles have appear ...

Stereoselective synthesis and isomerization of the indole alkaloid murrayacarine

A short and efficient stereoselective synthesis of the indole alkaloid murrayacarine is described, including studies on its acid-induced isomerization.

Oxidative Coupling of Indoline-2-thione or Oxindole: Formation of Cyclic and Acyclic Indole Trimers

Oxidation of indoline-2-thione using p-toluenesulfonyl azide produced a modest yield of the structurally novel cyclic sulfur containing indole trimer (12). In contrast, the oxidation of oxindole wi ...

Recent progress in the chemistry of sulfur-containing indoles

Publisher Summary This chapter presents a review on the recent progress in the chemistry of sulfur-containing indoles. The chemistry of sulfur-containing indoles has led to the development of a multitude of compounds displaying interesting structural features and potent biological activity profiles. The chapter discusses indoles possessing sulfur at C-2, at C-3, and both C-2 and C-3, respectively, and focuses on chemical studies, including some selected biologically oriented papers. The chapter discusses (1) indoles possessing sulfur at C-2, (2) indoles possessing sulfur at C-3, and (3) indoles possessing sulfur at both C-2 and C-3. The keto-enol/enolate interconversions of indoline-2-thiones and their oxa- or selena-analogues in aqueous media have been investigated recently. Indoline-2-thiones have been prepared via lithiation of certain 2-substituted anilines followed by reaction with CS2, or thiomethylation of 2-chloro-1-methylindole-3-carbonyl amides, followed by demethylation. A useful and mild general route to 3-arylthioindoles has been developed employing the reaction of the indolyl anion with diaryldisulfides in DMF, avoiding the use of highly reactive arenesulfenyl chlorides. A second sulfenylation of the readily available indol-3-yl sulfides provides a protocol for the regioselective synthesis of mixed 2,3-di(alkyl/arylthio)indoles, a process which was suggested to occur via an intermediate 3,3-dithiaindolenine species, which could later be isolated when the second sulfenylation was performed in the presence of a base.