Synthesis and stereochemistry of stereoisomeric 1,2,3-oxathiazino[4,3-a]isoquinolines

Abstract

The ring-closures of homocalycotomine and its 1Ј-and 2Ј-methyl-substituted diastereomers 3, 4 and 7, 8 with thionyl chloride or with sulfuryl chloride led to 1,2,3-oxathiazino[4,3-a]isoquinoline derivatives 9-11 and 18, 19 or to 15, 17 and 22, 23, respectively. The relative configurations and the predominant conformations of the cis 1 -transcis 2 conformational equilibrium were studied by means of 1 H-and 13 C-NMR spectroscopy, with the application of DNOE, 2D HSC and 2D-COSY measurements. In good agreement with the liquid-phase results, the X-ray investigations revealed that 9 and 10 have the cis 1 , while 18 has the trans-anellated stereostructure.

Synthesis and Conformational Analysis of Tetrahydroisoquinoline‐Fused 1,3,2‐Oxazaphospholidines and 1,2,3‐Oxathiazol­idines

“…The 1 H NMR spectra of the crude products indicated that the diastereomer of the 1,2,3‐oxathiazolo 2‐oxides containing the S=O bond and the hydrogen atom at the annelation point in the cis position predominates both in the angularly fused ( 5 ) and in the linearly fused regioisomer ( 11 ). In contrast with the homologous 9,10‐dimethoxy‐1,6,7,11b‐tetrahydro‐2 H ‐1,2,3‐oxathiazino[4,3‐ a ]isoquinoline 4‐oxide, for which the minor diastereomer decomposed during the chromatographic purification,12c both S ‐epimeric diastereomers ( 4 , 5 ) of the five‐membered analogue could be isolated by column chromatography. In the attempted cyclization of 7 with sulfuryl chloride, cyclic sulfamidate product 12 decomposed during the purification process.…”

Molecular Evolution Using Intramolecular Acyl Migration on myo‐Inositol Benzoates with Thermodynamic and Kinetic Selectors

“…The chemistry and stereochemistry of tetrahydroisoquinolines and of their phosphorus‐ and sulfur‐containing derivatives are of interest as a consequence of the potential biological activity of this class of compounds 1–6. Fused bicyclic7, 8 and tricyclic derivatives of 1,3,2‐oxazaphosphino‐9, 10 and 1,2,3‐oxathiazino[4,3‐ a ]isoquinoline11 analogues with nitrogen at the bridgehead position have been synthesized and their conformational analysis by different methods, e.g. nuclear magnetic resonance (NMR) spectroscopy in solution, X‐ray diffraction in the solid state and quantum chemical calculations in the gaseous state, has been carried out.…”

“…nuclear magnetic resonance (NMR) spectroscopy in solution, X‐ray diffraction in the solid state and quantum chemical calculations in the gaseous state, has been carried out. The heteroatoms and the substituents on the saturated ring moieties were both found to strongly influence the conformation of the polycyclic heterocycles 9–11…”

Synthesis and stereochemistry of 4-arylimino-1,3-oxazino- and 1,3-thiazino[4,3,a]isoquinolines

“…refs 9-11) deal with the synthesis of the closely analogous 1,3-oxazino-and 1,3-thiazino [4,3-a]isoquinolines. As a continuation of our systematic studies [5][6][7][8][9][10][11][12][13][14][15] on isoquinoline-fused 1,3-heterocycles, we now report on the synthesis of 1,3-oxazino-and 1,3-thiazino [4,3-a]isoquinolines. These compounds are interesting from both pharmacological and stereochemical points of view.…”

“…[1][2][3][4][5] The hetero atoms, the substituents on the saturated rings and the configurations of the substituted carbon atoms have been demonstrated to exert pronounced effects on the conformations of these compounds. [6][7][8] On the other hand, only a few papers (see e.g. refs 9-11) deal with the synthesis of the closely analogous 1,3-oxazino-and 1,3-thiazino [4,3-a]isoquinolines.…”