Synthesis and crystal structure of 5-methyl-2-(N-anabasinyl)-5,6-dihydro-1,3-thiazin-4-one from the alkaloid anabasine

Abstract

UDC 547.94;one was synthesized in one step from the alkaloid anabasine. Its structure was proved by IR and PMR spectroscopy, mass spectrometry, and an x-ray structure analysis.Keywords: anabasine alkaloid, methacryloylisothiocyanate, intramolecular heterocyclization, 5,6-dihydro-1,3-thiazin-4-one, x-ray structure analysis.We have previously synthesized thiourea derivatives of the alkaloids cytisine, anabasine, d-pseudoephedrine, and l-ephedrine [1][2][3]. Many thiourea derivatives based on these alkaloids are excellent synthons for synthesizing new heterocyclic derivatives [4,5]. It was found [6] during preparation of the thiosemicarbazide derivative of isonicotinic acid that reaction of the corresponding hydrazide with methacryloylisothiocyanate produced its intramolecular heterocyclization product, 5,6-dihydro-1,3-thiazin-4-one.Therefore, we investigated the reaction of anabasine with methacryloylisothiocyanate (1), which was prepared in situ (without isolation) by heating methacryloylchloride with potassium thiocyanate in acetone. The reaction occurred with intramolecular heterocyclization of the intermediate methacrylamide derivative 2 into the corresponding product 3. The reaction occurred under rather mild conditions at 25-30°C in acetone.The yield and purity of the synthesized derivative 5,6-dihydro-1,3-thiazin-4-one (3) varied depending on the rate and order of addition of the reagents. The most acceptable (up to 40%) yields of 3 were obtained with slow dropping of a freshly prepared acetone solution of 1 to a vigorously stirred solution of anabasine.Only trace amounts of heterocyclization product 3 could be detected with the reverse order of addition of reagents to the reaction mixture. Its amount increased with time as a result of gradual spontaneous intramolecular cyclization of 2. The reaction mixture contained after work up also several unidentified crystalline and oily side products with -NH, -SCN, and C=O groups (IR spectroscopy data). As a result, it was impossible to separate and characterize in a pure state the methacrylamide intermediate 2.

Synthesis, Structure and Molecular Docking of New 4,5-Dihydrothiazole Derivatives Based on 3,5-Dimethylpyrazole and Cytisine and Salsoline Alkaloids

“…Most thiourea and thioureide derivatives have not only valuable pharmacological properties and are used as antiepileptic drugs [ 51 ], antidiabetic [ 52 ], anti-cancer [ 53 ], anti-tuberculosis [ 54 ] and other therapeutically active substances [ 55 ], but they are also initial synthons in the synthesis of many sulfur-containing heterocycles [ 56 , 57 , 58 , 59 , 60 ].…”

Synthesis, Structure and Molecular Docking of New 4,5-Dihydrothiazole Derivatives Based on 3,5-Dimethylpyrazole and Cytisine and Salsoline Alkaloids

“…Most thiourea and thioureide derivatives have not only valuable pharmacological properties and are used as antiepileptic drugs [51], antidiabetic [52], anti-cancer [53], anti-tuberculosis [54] and other therapeutically active substances [55], but they are also initial synthons in the synthesis of many sulfur-containing heterocycles [56][57][58][59][60].…”