Controlling the Oxygenation Level of Hemoglobin by Using a Synthetic Receptor for 2,3‐Bisphosphoglycerate

Abstract

Der synthetische Rezeptor 1 mit Guanidinium‐Gruppen und einem Kupfer(II)‐Zentrum bindet 2,3‐Diphosphoglycerat (2,3‐BPG) unter physiologischen Bedingungen effektiv und selektiv (siehe Bild; C=grau, Cu=grün, N=blau, P=gelb, O=rot). Durch seine hohe Affinität verringert der Rezeptor die Konzentration von verfügbarem 2,3‐BPG und nimmt auf diese Weise Einfluss auf die Oxygenierung von Hämoglobin.

Nucleophilic Addition to Unsaturated Nitrogen

“…This mechanism is in accordance with the proposed reaction mechanism for the aldol reaction (see chapter 6.2 The Hayashi group investigated the a-aminoxylation of propanal with nitrosobenzene in the presence of 30 mol% l-proline as model reaction [12a]. [11] The effect of the amount of catalyst (which is high, approximately 30 mol%) on this model reaction was also studied. Investigation of a variety of solvents revealed that acetonitrile was preferred, giving the desired product (R)-13a in quantitative yield and with excellent enantioselectivity (98% ee).…”

“…Zhong rationalized the enantioselectivity by proposing an enamine mechanism which proceeds via the chair transition state shown in Figure 7.1 [11]. In this transition state, the Si face of an E enamine formed from the aldehyde and the catalyst l-proline approaches the less-hindered oxygen atom of nitrosobenzene leading to the chiral product with (R) configuration.…”

“…In addition to nucleophilic addition to NbN double bonds, very recently the Mac-Millan group, the Hayashi group, Zhong, and the Cordova group independently demonstrated that additions of aldehydes to the NbO double bond also are catalyzed by organocatalysts [10][11][12][13]. Nitrosobenzene was used as the NbO compound and l-proline as the organocatalyst.…”

“…Nitrosobenzene was used as the NbO compound and l-proline as the organocatalyst. The concept of the reaction is shown below in Scheme 7.7 [10][11][12][13]. It is worthy of note that the carbonyl component can be used directly without prior modification, which simplifies the process.…”

“…In parallel, Zhong reported the a-aminooxylation of aldehydes, and in-situ derivatization into 1,2-diols, also using l-proline as catalyst [11]. a-Aminooxylation of isovaleraldehyde with nitrosobenzene at room temperature with 20 mol% catalyst was studied as model reaction.…”