Stereoselective Synthesis of γ-Fluorinated α-Amino Acids Using 2-Hydroxy-3-pinanone as an Auxiliary

Laue, K. W.; Kröger, Stefan; Wegelius, Elina; Haufe, Günter

doi:10.1002/1099-0690(200011)2000:22<3737::aid-ejoc3737>3.3.co;2-1

Cited by 6 publications

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“…The key step of the synthesis is an asymmetric aldol reaction of the fluorinated aldehyde 3 with the enantiopure iminoglycinate 4 ( Scheme 1 ). The latter building block has already been used for the preparation of several γ-fluoro-α-amino acids [ 31 ]. This methodology, utilizing the corresponding ethyl iminoglycinate instead of 4 , was previously applied for the synthesis of natural D- erythro -sphingosine ( 1a ) [ 32 ], deuterium and tritium labeled sphingosines [ 33 ] and various other non-fluorinated sphingosine, sphinganine and phytosphingosine derivatives [ 34 ].…”

Section: Resultsmentioning

confidence: 99%

Stereoselective synthesis of (2S,3S,4Z)-4-fluoro-1,3-dihydroxy-2-(octadecanoylamino)octadec-4-ene, [(Z)-4-fluoroceramide], and its phase behavior at the air/water interface

Nikolova¹,

Haufe²

2008

Beilstein J. Org. Chem.

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Section: Resultsmentioning

confidence: 99%

Stereoselective synthesis of (2S,3S,4Z)-4-fluoro-1,3-dihydroxy-2-(octadecanoylamino)octadec-4-ene, [(Z)-4-fluoroceramide], and its phase behavior at the air/water interface

Nikolova¹,

Haufe²

2008

Beilstein J. Org. Chem.

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“…There are several examples in the literature where alkylation of imines derived from enantiomerically pure chiral ketones has afforded acyclic quaternary α-amino acids with highenantioselectivities, – and Crooks et al have used this technique to synthesize anabasine analogues and derivatives . Recognizing the potential of this modification to control the stereochemical outcome in the key alkylation step, we chose to use the (+)- and (−)-antipodes of 2-hydroxy-3-pinanone to synthesize the desired imines.…”

Section: Discussionmentioning

confidence: 99%

Synthesis of 2-(Pyridin-3-yl)-1-azabicyclo[3.2.2]nonane, 2-(Pyridin-3-yl)-1-azabicyclo[2.2.2]octane, and 2-(Pyridin-3-yl)-1-azabicyclo[3.2.1]octane, a Class of Potent Nicotinic Acetylcholine Receptor–Ligands

et al. 2008

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In an attempt to generate nicotinic acetylcholine receptor (nAChR) ligands selective for the alpha4beta2 and alpha7 subtype receptors we designed and synthesized constrained versions of anabasine, a naturally occurring nAChR ligand. 2-(Pyridin-3-yl)-1-azabicyclo[2.2.2]octane, 2-(pyridin-3-yl)-1-azabicyclo[3.2.2]nonane, and several of their derivatives have been synthesized in both an enantioselective and a racemic manner utilizing the same basic synthetic approach. For the racemic synthesis, alkylation of N-(diphenylmethylene)-1-(pyridin-3-yl)methanamine with the appropriate bromoalkyltetrahydropyran gave intermediates which were readily elaborated into 2-(pyridin-3-yl)-1-azabicyclo[2.2.2]octane and 2-(pyridin-3-yl)-1-azabicyclo[3.2.2]nonane via a ring opening/aminocyclization sequence. An alternate synthesis of 2-(pyridin-3-yl)-1-azabicyclo[3.2.2]nonane via the alkylation of N-(1-(pyridin-3-ylethylidene)propan-2-amine has also been achieved. The enantioselective syntheses followed the same general scheme, but utilized imines derived from (+)- and (-)-2-hydroxy-3-pinanone. Chiral HPLC shows that the desired compounds were synthesized in >99.5% ee. X-ray crystallography was subsequently used to unambiguously characterize these stereochemically pure nAChR ligands. All compounds synthesized exhibited high affinity for the alpha4beta2 nAChR subtype ( K i < or = 0.5-15 nM), a subset bound with high affinity for the alpha7 receptor subtype ( K i < or = 110 nM), selectivity over the alpha3beta4 (ganglion) receptor subtype was seen within the 2-(pyridin-3-yl)-1-azabicyclo[2.2.2]octane series and for the muscle (alpha1betagammadelta) subtype in the 2-(pyridin-3-yl)-1-azabicyclo[3.2.2]nonane series.

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“…Deprotection of the acid moiety and acidic hydrolysis gave (S)-MfeGly 33 (Scheme 9). 72,73 Wang et al used a chiral aspartic acid derivative for their synthesis of (S)-MfeGly 33. The free acid moiety of (S)-4-(benzyloxy)-2-((Boc)amino)-4-oxobutanoic acid was protected as the corresponding tert-butyl ester, and the benzyl protecting group was chemoselectively hydrogenated.…”

Section: T H Imentioning

confidence: 99%

“…Removal of the chiral auxiliary, hydrolysis of the ester and stirring in propene oxide generated (S)-2-amino-4-fluoropent-4-enoic acid 114 in 88% ee (Scheme 25). 109 Alternatively, Shenage et al established a synthetic approach for the asymmetric synthesis of 114 starting from enantiopure (S)-Boc-BMI 84,85 stereoselective alkylation of (S)-Boc-BMI with 2-fluoroallyl tosylate was performed in the presence of DMPU using LDA as a base, leading to a single diastereomer. Deprotection of the alkylation product was achieved in two steps and gave the desired product 114.…”

Section: T H Imentioning

confidence: 99%

Approaches to Obtaining Fluorinated α-Amino Acids

et al. 2019

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Fluorine does not belong to the pool of chemical elements that nature uses to build organic matter. However, chemists have exploited the unique properties of fluorine and produced countless fluoro-organic compounds without which our everyday lives would be unimaginable. The incorporation of fluorine into amino acids established a completely new class of amino acids and their properties, and those of the biopolymers constructed from them are extremely interesting. Increasing interest in this class of amino acids caused the demand for robust and stereoselective synthetic protocols that enable straightforward access to these building blocks. Herein, we present a comprehensive account of the literature in this field going back to 1995. We place special emphasis on a particular fluorination strategy. The four main sections describe fluorinated versions of alkyl, cyclic, aromatic amino acids, and also nickel-complexes to access them. We progress by one carbon unit increments. Special cases of amino acids for which there is no natural counterpart are described at the end of each section. Synthetic access to each of the amino acids is summarized in form of a table at the end of this article with the aim to make the information easily accessible to the reader.

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Stereoselective Synthesis of γ-Fluorinated α-Amino Acids Using 2-Hydroxy-3-pinanone as an Auxiliary

Cited by 6 publications

References 0 publications

Stereoselective synthesis of (2S,3S,4Z)-4-fluoro-1,3-dihydroxy-2-(octadecanoylamino)octadec-4-ene, [(Z)-4-fluoroceramide], and its phase behavior at the air/water interface

Stereoselective synthesis of (2S,3S,4Z)-4-fluoro-1,3-dihydroxy-2-(octadecanoylamino)octadec-4-ene, [(Z)-4-fluoroceramide], and its phase behavior at the air/water interface

Synthesis of 2-(Pyridin-3-yl)-1-azabicyclo[3.2.2]nonane, 2-(Pyridin-3-yl)-1-azabicyclo[2.2.2]octane, and 2-(Pyridin-3-yl)-1-azabicyclo[3.2.1]octane, a Class of Potent Nicotinic Acetylcholine Receptor–Ligands

Approaches to Obtaining Fluorinated α-Amino Acids

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