Studies towards lipid A: a synthetic strategy for the enantioselective preparation of 3-hydroxy fatty acids

Guaragna, Annalisa; Nisco, Mauro De; Pedatella, Silvana; Palumbo, Giovanni

doi:10.1016/j.tetasy.2006.10.023

Cited by 13 publications

(8 citation statements)

References 10 publications

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“…Although there have been a number of syntheses of (3 R )-hydroxy alkanoic acids reported in the literature to date, [10,11] we proposed a shorter route whereby the desired acid 5 could be accessed from the chiral homoallylic alcohol 16 via an oxidative cleavage-oxidation sequence (Scheme 1). Homoallylic alcohol 16 in turn could be prepared via an enantioselective allylation reaction as the key stereochemistry determining step from the commercially available aldehyde, decanal ( 17 ).…”

Section: Resultsmentioning

confidence: 99%

Total Synthesis of Fellutamide B and Deoxy-Fellutamides B, C, and D

Giltrap

Cergol²,

Pang³

et al. 2013

Marine Drugs

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The total syntheses of the marine-derived lipopeptide natural product fellutamide B and deoxy-fellutamides B, C, and D are reported. These compounds were accessed through a novel solid-phase synthetic strategy using Weinreb amide-derived resin. As part of the synthesis, a new enantioselective route to (3R)-hydroxy lauric acid was developed utilizing a Brown allylation reaction followed by an oxidative cleavage-oxidation sequence as the key steps. The activity of these natural products, and natural product analogues was also assessed against Mycobacterium tuberculosis in vitro.

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Section: Resultsmentioning

confidence: 99%

Total Synthesis of Fellutamide B and Deoxy-Fellutamides B, C, and D

Giltrap

Cergol²,

Pang³

et al. 2013

Marine Drugs

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“…Recently, the synthesis of 3-hydroxylauric acid by γ-alkylation of doubly deprotonated ethyl acetoacetate followed by reduction of the β-keto moiety and ester hydrolysis has been reported [11]. 3-Hydroxy fatty acids may be also synthesized via the opening of chiral long chain terminal epoxides by Me 3 SiCN in the presence of TBAF, followed by hydrolysis of the resulting nitriles [12]. Another approach employs the ring opening of chiral 2-(2-benzyloxyethyl)-oxirane by a long chain alkylmagnesium bromide, followed by functional group transformations to give 3-hydroxy fatty acids [13].…”

Section: Introductionmentioning

confidence: 99%

Enantioselective Organocatalysis-Based Synthesis of 3-Hydroxy Fatty Acids and Fatty γ-Lactones

et al. 2019

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3-Hydroxy fatty acids have attracted the interest of researchers, since some of them may interact with free fatty acid receptors more effectively than their non-hydroxylated counterparts and their determination in plasma provides diagnostic information regarding mitochondrial deficiency. We present here the development of a convenient and general methodology for the asymmetric synthesis of 3-hydroxy fatty acids. The enantioselective organocatalytic synthesis of terminal epoxides, starting from long chain aldehydes, is the key-step of our methodology, followed by ring opening with vinylmagnesium bromide. Ozonolysis and subsequent oxidation leads to the target products. MacMillan’s third generation imidazolidinone organocatalyst has been employed for the epoxide formation, ensuring products in high enantiomeric purity. Furthermore, a route for the incorporation of deuterium on the carbon atom carrying the hydroxy group was developed allowing the synthesis of deuterated derivatives, which may be useful in biological studies and in mass spectrometry studies. In addition, the synthesis of fatty γ-lactones, corresponding to 4-hydroxy fatty acids, was also explored.

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“…Optically pure 3-hydroxy carboxylic acids and their derivatives are important chiral synthons used for the synthesis of a number of pharmaceuticals such as fluoxetine, b-lactams, pheromones, bblockers, lipid A and L-carnitine (Guaragna et al, 2006;Hu et al, 2007;Padhi et al, 2006;Spengler and Albericio, 2008). They have been prepared via lipase-catalyzed transesterification resolution of (R,S)-3-hydroxy carboxylic esters in organic solvents or hydrolysis at the 3-O-acyl group in the aqueous solution (Bornscheuer et al, 1993;Hoff and Anthonsen, 1999;Huerta and Backvall, 2001;Kaga et al, 1998;Nascimento et al, 2003;Xu and Yuan, 2005).…”

Section: Introductionmentioning

confidence: 99%