- Asymmetric Reductive Carbocyclization Using Engineered Ene Reductases
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Ene reductases from the Old Yellow Enzyme (OYE) family reduce the C=C double bond in α,β-unsaturated compounds bearing an electron-withdrawing group, for example, a carbonyl group. This asymmetric reduction has been exploited for biocatalysis. Going beyond its canonical function, we show that members of this enzyme family can also catalyze the formation of C?C bonds. α,β-Unsaturated aldehydes and ketones containing an additional electrophilic group undergo reductive cyclization. Mechanistically, the two-electron-reduced enzyme cofactor FMN delivers a hydride to generate an enolate intermediate, which reacts with the internal electrophile. Single-site replacement of a crucial Tyr residue with a non-protic Phe or Trp favored the cyclization over the natural reduction reaction. The new transformation enabled the enantioselective synthesis of chiral cyclopropanes in up to >99 % ee.
- Heckenbichler, Kathrin,Schweiger, Anna,Brandner, Lea Alexandra,Binter, Alexandra,Toplak, Marina,Macheroux, Peter,Gruber, Karl,Breinbauer, Rolf
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supporting information
p. 7240 - 7244
(2018/06/15)
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- Callipeltosides A, B and C: Total Syntheses and Structural Confirmation
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Since their isolation almost 20 years ago, the callipeltosides have been of long standing interest to the synthetic community owing to their unique structural features and inherent biological activity. Herein we present our full research effort that has led to the synthesis of these molecules. Key aspects of our final strategy include 1) synthesis of the C1-C9 pyran core (5) using an AuCl3-catalysed cyclisation; 2) formation of C10-C22 vinyl iodide (55) by sequential bidirectional Stille reactions and 3) diastereoselective union of these advanced fragments by means of an alkenylzinc addition (d.r.=91:9 at C9). The common callipeltoside aglycon (4) was completed in a further five steps. Following this, all three sugar fragments were appended to provide the entire callipeltoside family. In addition to this, D-configured callipeltose B was synthesised and appended to the callipeltoside aglycon. The 1H NMR spectrum of this molecule was found to be significantly different to the natural isolate, further supporting our assignment of callipeltoside B (2). Easy as A, B, C: The entire callipeltoside family of natural products have been synthesised in a highly convergent manner. This account details our full research effort and presents further evidence to aid in the stereochemical assignment of the glycosidic linkages present in callipeltosides B and C (see scheme).
- Frost, James R.,Pearson, Colin M.,Snaddon, Thomas N.,Booth, Richard A.,Turner, Richard M.,Gold, Johan,Shaw, David M.,Gaunt, Matthew J.,Ley, Steven V.
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supporting information
p. 13261 - 13277
(2015/09/15)
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- CYCLOPROPYL AMINE DERIVATIVES
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Compounds of formula (I) are useful in treating conditions or disorders prevented by or ameliorated by histamine-3 receptor ligands. Also disclosed are pharmaceutical compositions comprising the histamine-3 receptor ligands, methods for using such compoun
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Page/Page column 75
(2008/06/13)
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- Enantioselective cyclopropanation of allylic alcohols with dioxaborolane ligands: Scope and synthetic applications
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A very effective chiral controller has been found for the conversion of allylic alcohols into the corresponding enantiomerically enriched cyclopropanes using bis(iodomethyl)zinc. A variety of chiral, nonracemic cyclopropylmethanols could be obtained according to this method. This methodology was extended with success to the cyclopropanation of unconjugated and conjugated polyenes and homoallylic alcohols. The cyclopropanation of allylic carbamates has also been investigated with this system, but it was found that enantioenriched cyclopropylmethylamines are best prepared from enantioenriched cyclopropylmethanols.
- Charette, André B.,Juteau, Hélène,Lebel, Hélène,Molinaro, Carmela
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p. 11943 - 11952
(2007/10/03)
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