The Asymmertric Synthesis Of Piperidine Alkaloid(+)-Cassine,(+)-Spicigerine And Their C-3 Epimers

Piperidine structure widely exists in natural products, pharmaceutical molecules and can been see in many complicated alkaloids. Most of the compounds who contain piperidine ring received the attentions of many research group because of their important biological activity. 2, 6-Disubstituted piperidinol alkaloids are an important part of the piperidine alkaloid, which were isolated from Cassia and Prosopis species and they have similar structures. The dissertation aims to construct a efficient synthetic route of 2,6-disubstituted piperidinol alkaloids and used as the synthesis of(+)-Cassine、(+)-Spicigerine and their C-3 epimers. The dissertation contains the following two parts of work:The following two parts of research results was obtained in this dissertation. Refering to our addition-cyclization tandem protocol, we prepared high stereoselectively trans-3- hydroxyl-2-methyl-6-piperidone. On the basis of the asymmetric allylation reaction of allyl silicon reagents with N, O-acetal catalyzed by Lewis acid, we prepared high stereoselectively cis-2, 6-disubbstitutent piperid-3-ol.Carried out the asymmetric research of(+)-Cassine、(+)-Spicigerine and their epimers 3-epi-(+)-Cassine、3-epi-(+)-Spicigerine.Through the olefin metathesis reaction of compounds 82/83 with undec-10-en-2-one 103 seprately, we obtained compounds 102/104. Then reduce double bond, deprotect Cbz protecting groups,(+)-Cassine、 3-epi-(+)-Cassine were achieved with the 6.1%, 5.6% overall yield over 16 steps respectively.Through the olefin metathesis reaction of compounds 82/83 with benzyl dec-9-enoate 265 seprately, we obtained compounds 264/266. Then reduce double bond, deprotect Cbz protecting groups,(+)-Spicigerine, 3-epi-(+)-Spicigerine were achieved with the 6.6%, 6.6% overall yield over 16 steps respectively.