Total syntheses of (+)-australine and (-)-7-epialexine.
Total syntheses of (+)-australine and (-)-7-epialexine.
复制标题
( )-autraline 和 (-)-7-epialexine 的全合成。
DOI：
10.1021/jo000689q
复制
发表时间：
2000
期刊：
影响因子：
--
通讯作者：
Hines,JV
中科院分区：
文献类型：
--
作者：
Pearson,WH;Hines,JV
Three approaches were examined for the synthesis of 3-(hydroxymethyl)pyrrolizidines, a class of compounds that includes the polyhydroxylated pyrrolizidine alkaloids alexine (1), australine (2), and various stereoisomers of thereof. In the first approach, the intramolecular cycloaddition of an azide onto an electron-rich 1,3-diene bearing a terminal alkoxymethyl substituent (i.e.,21) afforded the dehydropyrrolizidines22aand22b, with22apredominating. A rationale for this stereoselectivity was proposed. Transformation of the major diastereomer22ainto a natural 3-(hydroxymethyl)pyrrolizidine was not possible due to difficulties encountered in transforming the phenyl vinyl sulfide functionality into other useful functional groups. A second approach was examined, wherein the intramolecular cycloaddition of an azide with an optically pure S-t-Bu-substituted diene (i.e.,30) was found to produce the pyrrolizidine31. In this case, the alkoxymethyl substituent was incorporated into the tether between the azide and the diene, rather than on the diene itself. A key transformation in the synthesis of the diene30was the use of the allylic borane R2BCH2CHC(TMS)(StBu) for the stereoselective conversion of thed-arabinose-derived azido aldehyde28to theE-isomer of30. The cyclization of30to31also produced the bicyclic triazene32, the result of 1,3-dipolar cycloaddition of the azide onto the distal double bond of the diene. Again, difficulties in transformation of the vinyl sulfide functionality of31into useful oxygen functionality limited this approach to naturally occurring 3-(hydroxymethyl)pyrrolizidines. A third approach to these compounds was successful. The transformation ofl-xylose into the azido epoxy tosylate46was accomplished using two Wittig reactions and an epoxidation, in addition to other standard functional group manipulations. Reductive double-cyclization of46afforded the pyrrolizidines47aand47b, which were debenzylated to afford (+)-australine2and (−)-7-epialexine4, respectively. In the preliminary report of this work, erroneous spectroscopic data in the original literature on the structural assignment of australine led to the conclusion that the synthetic material obtained herein was actually (+)-7-epiaustraline. Recently corrected spectroscopic data have appeared which verify that (+)-australine2was indeed synthesized for the first time.
