Asymmetric synthesis of D-fagomine and its diastereoisomers

TETRAHEDRON

卷:74

Article

Davies, Stephen G.¹  Fletcher, Ai M.¹  Kennedy, Matthew S.¹  Roberts, Paul M.¹  Thomson, James E.¹ 

[1] Univ Oxford, Dept Chem, Chem Res Lab, Mansfield Rd, Oxford OX1 3TA, England

关键词: D-fagomine;    D-3-epi-fagomine;    D-4-epi-fagomine;    D-5-epi-fagomine;    Asymmetric synthesis;    Lithium amide;   

DOI  :  10.1016/j.tet.2018.10.073

来源: Elsevier

【 摘 要 】

A divergent strategy for the asymmetric syntheses of D-fagomine and three of its diastereoisomers has been developed. The diastereoselective conjugate addition of an enantiopure lithium amide to an alpha,beta-unsaturated ester was used as the key step to install the correct configuration required for the C(5)stereogenic centre within the targets. In situ enolate oxidation generated the corresponding anti-alpha-hydroxy-beta-amino ester, which possessed the correct configuration required for the C(4)-stereogenic centre within both D-fagomine and D-3-epi-fagomine. Subsequent epimerisation of this key anti-alpha-hydroxy-beta-amino ester upon oxidation and diastereoselective reduction gave the corresponding syn-alpha-hydroxy-fiamino ester, which possessed the correct configuration required for the C(4)-stereogenic centre within both D-4-epi-fagomine and D-5-epi-fagomine. Elaboration of both alpha-hydroxy-beta-amino esters upon reduction to the corresponding aldehydes followed by aldol reaction generated the requisite C(3)stereogenic centres within the target compounds, then cyclisation and deprotection gave the enantiopure iminosugars in good overall yields, as single diastereoisomers (>99:1 dr). (C) 2018 Elsevier Ltd. All rights reserved.

【 授权许可】

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