Diastereoselective Synthesis of Piperidine Imino Sugars Using Aldol Additions of Metalated Bislactim Ethers to Threose and Erythrose Acetonides
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- 作者：Marí ; a Ruiz ; Tania M. Ruanova ; Olga Blanco ; Fá ; tima Nú ; ñ ; ez ; Cristina Pato ; Vicente Ojea
- 刊名：Journal of Organic Chemistry
- 出版年：2008
- 出版时间：March 21, 2008
- 年：2008
- 卷：73
- 期：6
- 页码：2240 - 2255
- 全文大小：506K
- 年卷期：v.73,no.6(March 21, 2008)
- ISSN：1520-6904
文摘
A general strategy for the synthesis of 1-deoxy-azasugars from a chiral glycine equivalent and 4-carbonbuilding blocks is described. Diastereoselective aldol additions of metalated bislactim ethers to matchedand mismatched erythrose or threose acetonides and intramolecular N-alkylation (by reductive aminationor nucleophilic substitution) were used as key steps. The dependence of the yield and the asymmetricinduction of the aldol addition with the nature of the metallic counterion of the azaenolate and the 
-alkoxyprotecting group for the erythrose or threose acetonides has been studied. The stereochemical outcomeof the aldol additions with tin(II) azaenolates has been rationalized with the aid of density functionaltheory (DFT) calculations. In accordance with DFT calculations with model glyceraldehyde acetonides,high trans,syn,anti-selectivitity for the matched pairs and moderate to low trans,anti,anti-selectivity forthe mismatched ones may originate from (1) the intervention of solvated aggregates of tin(II) azaenolateand lithium chloride as the reactive species and (2) favored chair-like transition structures with a Cornforth-like conformation for the aldehyde moiety. DFT calculations indicate that aldol additions to erythroseacetonides proceed by an initial deprotonation, followed by coordination of the alkoxy-derivative to thetin(II) azaenolate and final reorganization of the intermediate complex through pericyclic transitionstructures in which the erythrose moiety is involved in a seven-membered chelate ring. The preparativeutility of the aldol-based approach was demonstrated by application in concise routes for the synthesisof the glycosidase inhibitors 1-deoxy-D-allonojirimycin, 1-deoxy-L-altronojirimycin, 1-deoxy-D-gulonojirimycin, 1-deoxy-D-galactonojirimycin, 1-deoxy-L-idonojirimycin and 1-deoxy-D-talonojirimycin.
-alkoxyprotecting group for the erythrose or threose acetonides has been studied. The stereochemical outcomeof the aldol additions with tin(II) azaenolates has been rationalized with the aid of density functionaltheory (DFT) calculations. In accordance with DFT calculations with model glyceraldehyde acetonides,high trans,syn,anti-selectivitity for the matched pairs and moderate to low trans,anti,anti-selectivity forthe mismatched ones may originate from (1) the intervention of solvated aggregates of tin(II) azaenolateand lithium chloride as the reactive species and (2) favored chair-like transition structures with a Cornforth-like conformation for the aldehyde moiety. DFT calculations indicate that aldol additions to erythroseacetonides proceed by an initial deprotonation, followed by coordination of the alkoxy-derivative to thetin(II) azaenolate and final reorganization of the intermediate complex through pericyclic transitionstructures in which the erythrose moiety is involved in a seven-membered chelate ring. The preparativeutility of the aldol-based approach was demonstrated by application in concise routes for the synthesisof the glycosidase inhibitors 1-deoxy-D-allonojirimycin, 1-deoxy-L-altronojirimycin, 1-deoxy-D-gulonojirimycin, 1-deoxy-D-galactonojirimycin, 1-deoxy-L-idonojirimycin and 1-deoxy-D-talonojirimycin.