An efficient synthesis of (R)-3-hydroxytetradecanoic acid

Huang, Guangfei; Hollingsworth, Rawle I.

doi:10.1016/s0957-4166(98)00441-8

Cited by 26 publications

(20 citation statements)

References 12 publications

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“…The strategy was also applied to the synthesis of the 3( S )‐enantiomer, and an analog with two extra carbon atoms on the FA chain that is, compound 3( R )‐PAHMyr .In this strategy, the free carboxylic group is generated at the last step of the synthesis after the acylation step. Chiral pool synthesis starting from commercially available ( S )‐β‐hydroxy‐γ‐butyrolactone 40 or optically active epichlorohydrin.Scheme is given as an example. The ( S )‐β‐hydroxy‐γ‐butyrolactone 40 was converted to iodohydrin 42 , then epoxide followed by epoxide ring‐opening with the Grignard reagent derived from n ‐bromodecane and saponification. The enantiomeric excess reached 99 % ee , with excellent overall yields.The route starting from ( S )‐epichlorhydrin involves a copper‐mediated epoxide ring opening with the Grignard reagent derived from n ‐bromodecane, epoxide re‐formation and re‐opening with sodium cyanide.…”

Section: Fahfas Are Endogenous Lipidsmentioning

confidence: 99%

Branched Fatty Acyl Esters of Hydroxyl Fatty Acids (FAHFAs), Appealing Beneficial Endogenous Fat against Obesity and Type‐2 Diabetes

Balas

Feillet‐Coudray

Durand

2018

Chemistry A European J

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After a brief overview of the biological significance of FAHFAs, the present Minireview highlights the different strategies developed for their chemical syntheses. The term "FAHFAs" has been introduced in 2014 for fatty acyl esters of hydroxyl fatty acids, found in adipocytes, with antidiabetic properties. However, many other natural products contain this type of branched lipids in their structure. This review was then extended to the synthesis of these subunits, even though the length of the lipid chains and the location of the ester linkages are different, since the developed strategies may be applied to the synthesis of "FAHFA".

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Section: Fahfas Are Endogenous Lipidsmentioning

confidence: 99%

Branched Fatty Acyl Esters of Hydroxyl Fatty Acids (FAHFAs), Appealing Beneficial Endogenous Fat against Obesity and Type‐2 Diabetes

Balas

Feillet‐Coudray

Durand

2018

Chemistry A European J

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“…3C) was synthesized as reported (37, 38). Compound 4 was coupled with hydroxylamine hydrochloridein the presence of EDC/DIPEA to form 5 which, upon reaction with the corresponding Grignard or lithium-derived agent, yielded 6 and 7 in good yield.…”

Section: Methodsmentioning

confidence: 99%

Diacyltransferase Activity and Chain Length Specificity of Mycobacterium tuberculosis PapA5 in the Synthesis of Alkyl β-Diol Lipids

Touchette¹,

Bommineni²,

Bovi³

et al. 2015

Biochemistry

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Although classified as Gram-positive bacteria, Corynebacterineae possess an asymmetric outer membrane that imparts structural and thereby physiological similarity to more distantly related Gram-negative bacteria. Like lipopolysaccharide in Gram-negative bacteria, lipids in the outer membrane of Corynebacterineae have been associated with the virulence of pathogenic species such as Mycobacterium tuberculosis (Mtb). For example, Mtb strains that lack long, branched-chain alkyl esters known as dimycocerosates (DIMs) are significantly attenuated in model infections. The resultant interest in the biosynthetic pathway of these unusual virulence factors has led to the elucidation of many of the steps leading to the final esterification of the alkyl beta-diol, phthiocerol, with branched-chain fatty acids known as mycocerosates. PapA5 is an acyltransferase implicated in these final reactions. We here show that PapA5 is indeed the terminal enzyme in DIM biosynthesis by demonstrating its dual esterification activity and chain-length preference using synthetic alkyl beta-diol substrate analogues. Applying these analogues to a series of PapA5 mutants, we also revise a model for the substrate binding within PapA5. Finally, we demonstrate that the Mtb Ser/Thr kinases PknB and PknE modify PapA5 on three overlapping Thr residues and a fourth Thr is unique to PknE phosphorylation. These results clarify the DIM biosynthetic pathway and indicate post-translational modifications that warrant further elucidation for their roles in regulation DIM biosynthesis.

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“…enhancement (to >99.8%) by crystallization of 12 [29]. Other methods for the preparation of 11 were also examined, including copper-catalyzed Grignard addition to epoxybutyrate 13 (99.9% e.e., prepared in three steps from maltose) [30], but generally found to be less suitable, particularly for larger scale preparations. However, this latter method proved useful for the preparation ofunsaturated derivatives of 11, which are inaccessible via catalytic hydrogenation [31].…”

Section: IImentioning

confidence: 99%

Synthetic TLR4-active Glycolipids as Vaccine Adjuvants and Stand-alone Immunotherapeutics

Johnson¹

2008

CTMC

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The design of vaccine adjuvants and stand-alone immunotherapeutics has historically been a mix of alchemy and accident partly because of the complex nature of the molecular mechanisms involved in immune system function. The recent discovery of pattern recognition receptors and toll-like receptors (TLRs) in particular on cells of the immune system has shown the important role that stimulation of these cell receptors by microbial products plays in both innate and adaptive immune responses. Considerable effort has been directed at developing pharmaceutically acceptable mimetics of many TLR-active natural products, including the main cell-surface component of Gram-negative bacteria: lipopolysaccharide (LPS). LPS and its active principle, lipid A, are potent stimulators of host defense systems via their interaction with TLR4. However, the profound pyrogenicity and lethal toxicity of LPS and lipid A have precluded their medicinal use. Structure/activity investigations on natural S. minnesota R595 lipid A and its derivatives have led to the development of a novel class of synthetic lipid A mimetics known as aminoalkyl glucosaminide phosphates (AGPs). This review discusses the evolution of the AGPs and related TLR4-active glycolipids with emphasis on structure/activity relationships in the AGP series and pre-clinical/clinical development of selected AGPs, including the potent vaccine adjuvant RC-529.

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An efficient synthesis of (R)-3-hydroxytetradecanoic acid

Cited by 26 publications

References 12 publications

Branched Fatty Acyl Esters of Hydroxyl Fatty Acids (FAHFAs), Appealing Beneficial Endogenous Fat against Obesity and Type‐2 Diabetes

Branched Fatty Acyl Esters of Hydroxyl Fatty Acids (FAHFAs), Appealing Beneficial Endogenous Fat against Obesity and Type‐2 Diabetes

Diacyltransferase Activity and Chain Length Specificity of Mycobacterium tuberculosis PapA5 in the Synthesis of Alkyl β-Diol Lipids

Synthetic TLR4-active Glycolipids as Vaccine Adjuvants and Stand-alone Immunotherapeutics

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