Bulgecinine의 선구물질인 (4S,5R)-1-acetyl-2-formyl-5-benzyloxymethyl-4-pyrrolidinol (15)을 diacetone-D-glucose로부터 합성하였다. Barton 탈산소화 반응, C-5에서의 반전, $-N_3$ 도입과 환원 및 C-2에서의 고리 형성을 통해 bulgecinine의 핵심 중간체인 두 고리 화합물 (6R)-6-Ο-benzyloxymethyl-(3R)-3-methoxy-2-oxa-5-azabicyclo-[2,2,1]heptane (13)을 합성하였다. 화합물 13을 N-아세틸화 후 산가수분해하여 얻은 bulgecinine 선구물질은 토토머화가 수반되어 (2S,4S,5R)-pyrrolidinol 유도체 15와 함께 (2S,4S,5R)-부분 입체 이성질체도 얻어졌다.
A precursor of bulgecinine, (4S,5R)-1-acetyl-2-formyl-5-benzyloxymethyl-4-pyrrolidinol (15) has been synthesized from diacetone-D-glucose. Barton deoxygenation, conversion to an L-sugar and displacement with $N_3^-$ at C-5, and one-pot reductive cyclization at C-2 produced (6R)-6-Ο-benzyloxymethyl-(3R)-3-methoxy-2-oxa-5-azabicyclo-[2,2,1]heptane(13), a key intermediate for bulgecinine. N-Acetylation and acid hydrolysis of 13 furnished a precursor of bulgecinine, (2S,4S,5R)-pyrrolidinol derivative 15 and its (2R,4S,5R)-diastereomer.
