Dragovich Peter S, Zhou Ru, Prins Thomas J
Pfizer Global Research and Development-La Jolla/Agouron Pharmaceuticals, Inc., 10777 Science Center Drive, San Diego, California 92121-1111, USA.
J Org Chem. 2002 Feb 8;67(3):741-6. doi: 10.1021/jo010712n.
The eleven-step preparation of the bicyclic 2-pyridone dipeptide mimetic 1 [(3S)-6-(benzyloxycarbonylamino)-5-oxo-1,2,3,5-tetrahydroindolizine-3-carboxylic acid] in optically active form (60% ee) is described. Key steps in the synthesis of 1 include the osmium-catalyzed asymmetric dihydroxylation of olefin 13 [(6-but-3-enyl-2-methoxypyridin-3-yl)carbamic acid benzyl ester] and the intramolecular cyclization of protected diol 19 [(3'R)-[6-[4'-(tert-butyldimethylsilanyloxy)-3'-hydroxybutyl]-2-methoxypyridin-3-yl]carbamic acid benzyl ester] to afford the pyridinium salt 20 [(3S)-[3-(tert-butyldimethylsilanyloxymethyl)-5-methoxy-2,3-dihydro-1H-indolizin-6-yl]carbamic acid benzyl ester trifuoromethanesulfonic acid salt]. Several alternate methods to prepare olefin 13 are also discussed.
描述了光学活性形式（对映体过量60%）的双环2-吡啶酮二肽模拟物1[（3S）-6-（苄氧羰基氨基）-5-氧代-1,2,3,5-四氢吲哚嗪-3-羧酸]的十一步制备方法。1的合成中的关键步骤包括烯烃13[（6-丁-3-烯基-2-甲氧基吡啶-3-基）氨基甲酸苄酯]的锇催化不对称二羟基化以及受保护的二醇19[（3'R）-[6-[4'-（叔丁基二甲基硅烷氧基）-3'-羟基丁基]-2-甲氧基吡啶-3-基]氨基甲酸苄酯]的分子内环化，以得到吡啶鎓盐20[（3S）-[3-（叔丁基二甲基硅烷氧基甲基）-5-甲氧基-2,3-二氢-1H-吲哚嗪-6-基]氨基甲酸苄酯三氟甲磺酸盐]。还讨论了制备烯烃13的几种替代方法。
