A Novel Approach for the Synthesis of (R) and (S)-Nicotine  

作　　者：Rohith Kumar Agarthimoole Sahir Gagan Sudesna Parida Tarur Konikkaledom Dinesh Maheswaran S. Karatholuvhu Namasivayam Palani Soumitra Mukherjee Rohith Kumar Agarthimoole;Sahir Gagan;Sudesna Parida;Tarur Konikkaledom Dinesh;Maheswaran S. Karatholuvhu;Namasivayam Palani;Soumitra Mukherjee(ITC Limited, ITC Life Sciences and Technology Centre, Peenya Industrial Area, Phase I, Bangalore, India;Presently at Department of Atmospheric Sciences, Texas A&M University, College Station, Texas, USA)

机构地区：[1]ITC Limited, ITC Life Sciences and Technology Centre, Peenya Industrial Area, Phase I, Bangalore, India [2]Presently at Department of Atmospheric Sciences, Texas A&M University, College Station, Texas, USA

出　　处：《International Journal of Organic Chemistry》2022年第4期189-199,共11页有机化学国际期刊（英文）

摘　　要：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.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.

关 键 词：NICOTINE IBUPROFEN DIASTEREOMERS Column Chromatography Chiral Purity 

分 类 号：O621[理学—有机化学]