Synthesis of the orthogonally protected amino alcohol Phaol and analogs
Jo Nelissen1, Koen Nuyts, Wim Dehaen
1Molecular Design and Synthesis, Department of Chemistry, K.U.Leuven, Celestijnenlaan 200F, box 2404, 3001 Leuven, Belgium.
Abstract:
The development of a multigram synthesis of the orthogonally protected amino acid-derived Phaol [2-{[(2S)-2-amino-3-phenylpropyl]amino}ethanol] is described. The goal of this work is to synthesize an orthogonally protected Phaol in a multigram scale up to 10 g (Cbz-Phaol), so it can be used in solution-based peptide synthesis of peptaibols. Two synthetic schemes were proposed and examined. Between the reduction-coupling and the coupling-reduction scheme, the latter gave the best results. A two-step synthesis affords easily purifiable products. Several analogs were synthesized using this methodology. All the molecules were orthogonally protected, so that they can be used in peptide synthesis. Deprotection posed no problems.
Related Concept Videos
Preparation of 1° Amines: Gabriel Synthesis
Strong bases like NaOH or KOH deprotonate the phthalimide to form the corresponding anion, which acts as a nucleophile. Further, the anion attacks an...
Protection of Alcohols
Protection
It defines a protecting group as the masking agent to make the more reactive species inert to a given set of conditions. This concept is depicted via the illustration of liquid flow through different outlets in an assembly of pipes. The analogy helps to understand the role...
Preparation of 1° Amines: Azide Synthesis
Azide ions act as good nucleophiles and react with unhindered alkyl halides to form alkyl azides. Alkyl azides do not participate in further nucleophilic substitution reactions, thereby eliminating the chances of polyalkylated products. Alkyl azides are reduced by hydride-based reducing agents, like lithium aluminum...
Alkylation of β-Diester Enolates: Malonic Ester Synthesis
ortho–para-Directing Activators: –CH3, –OH, –⁠NH2, –OCH3
Ethers from Alcohols: Alcohol Dehydration and Williamson Ether Synthesis
Ethers can be prepared from organic compounds by various methods. Some of them are discussed below,
Preparation of Ethers by Alcohol Dehydration
In this method, in the presence of protic acids, alcohol dehydrates to produce alkenes and ethers under different conditions. For example, in the presence of sulphuric acid, dehydration of ethanol at 413 K yields ethoxyethane, whereas it yields ethene at 443 K.


