Nicotine is an alkaloid mainly found in leaves of tobacco and is used therapeutically for patients seeking relief from tobacco dependence in the form of products such as gums, patches, lozenges etc. In these products,...Nicotine is an alkaloid mainly found in leaves of tobacco and is used therapeutically for patients seeking relief from tobacco dependence in the form of products such as gums, patches, lozenges etc. In these products, majorly nicotine derived from tobacco is used which is inherently contaminated with undesirable nicotine related substances as impurities at low levels and is difficult to remove. Hence, use of synthetic nicotine is considered as an option which will be devoid of such impurities. In this work, a short and efficient synthesis of (R) and (S) nicotine was achieved by leveraging a key esterification between racemic homoallylic alcohol intermediate (2) and (S)-Ibuprofen (3) to produce diastereomers (5a) and (5b) which were easily separable under standard column chromatography conditions. Use of (S)-Ibuprofen (3) as a chiral resolving agent constitutes a novel approach which was not reported earlier. A subsequent hydrolysis of the diastereomers furnished the homoallylic alcohol intermediates (S)-6a and (R)-6a with high enantiopurity, which was effectively translated to the corresponding (R)-nicotine and (S)-nicotine respectively.展开更多
文摘Nicotine is an alkaloid mainly found in leaves of tobacco and is used therapeutically for patients seeking relief from tobacco dependence in the form of products such as gums, patches, lozenges etc. In these products, majorly nicotine derived from tobacco is used which is inherently contaminated with undesirable nicotine related substances as impurities at low levels and is difficult to remove. Hence, use of synthetic nicotine is considered as an option which will be devoid of such impurities. In this work, a short and efficient synthesis of (R) and (S) nicotine was achieved by leveraging a key esterification between racemic homoallylic alcohol intermediate (2) and (S)-Ibuprofen (3) to produce diastereomers (5a) and (5b) which were easily separable under standard column chromatography conditions. Use of (S)-Ibuprofen (3) as a chiral resolving agent constitutes a novel approach which was not reported earlier. A subsequent hydrolysis of the diastereomers furnished the homoallylic alcohol intermediates (S)-6a and (R)-6a with high enantiopurity, which was effectively translated to the corresponding (R)-nicotine and (S)-nicotine respectively.
