A glycal approach towards an efficient and stereodivergent synthesis of polyhydroxypyrrolidines

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• 作者：Vipin Kumar and Namakkal G. Ramesh
• 关键词：Azasugars ; Glycosidase inhibitors ; Polyhydroxypyrrolidines ; Glycals ; Mitsunobu cyclization
• 刊名：Tetrahedron
• 出版年：2006
• 出版时间：20 February 2006
• 年：2006
• 卷：62
• 期：8
• 页码：1877-1885
• 全文大小：234 K

文摘

A stereo-defined synthesis of two diastereomers of polyhydroxypyrrolidines from 3,4,6-tri-O-benzyl-d-glucal g>4g> involving a cleavage–recyclization strategy is reported. Hemiacetal g>7g> obtained from glucal g>4g>, upon reduction with LiAlH₄ afforded diol g>8g>. Selective acetylation of g>8g> to g>11g>, followed by Mitsunobu cyclization yielded the diversely protected polyhydroxypyrrolidine g>12g>. Oxidation of g>11g> and subsequent stereoselective reduction led to g>20g>, the C-5 epimer of g>11g>, which upon Mitsunobu cyclization gave polyhydroxypyrrolidine g>21g>. Selective deprotection of the acetyl groups of g>12g> and g>21g> were carried out using Na₂CO₃ in MeOH. Polyhydroxypyrrolidines g>12g> and g>21g> upon heating with an excess of Mg in MeOH underwent simultaneous N-detosylation and deacetylation to afford amino alcohols g>15g> and g>24g>, respectively, in quantitative yield. Catalytic hydrogenation of g>15g> and g>24g> provided quantitatively the polyhydroxypyrrolidines g>2g> and g>3g>, respectively.