6168-83-8Relevant academic research and scientific papers
SYNTHESIS OF 3-HYDROXYBUTYRYL 3-HYDROXYBUTYRATE AND RELATED COMPOUNDS
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Paragraph 0308; 0320-0324, (2021/04/02)
In various embodiments methods of preparing hydroxybutyryl 3-hydroxybutyrate and related compounds are provided along with methods of use thereof.
PANTETHEINE DERIVATIVES AND USES THEREOF
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Paragraph 2121, (2020/06/19)
The present disclosure relates to compounds of Formula (I), (II), or (II'): (I), (II), (II'), and pharmaceutically acceptable salts or solvates thereof. The present disclosure also relates to pharmaceutical compositions comprising the compounds and therapeutic and diagnostic uses of the compounds and pharmaceutical compositions.
Process Optimisation Studies and Aminonitrile Substrate Evaluation of Rhodococcus erythropolis SET1, A Nitrile Hydrolyzing Bacterium
Coady, Tracey M.,Coffey, Lee,Kinsella, Michael,Lennon, Claire M.,Mareya, Tatenda M.,O'Reilly, Catherine
, p. 512 - 520 (2020/10/02)
A comprehensive series of optimization studies including pH, solvent and temperature were completed on the nitrile hydrolyzing Rhodococcus erythropolis bacterium SET1 with the substrate 3-hydroxybutyronitrile. These identified temperature of 25 °C and pH of 7 as the best conditions to retain enantioselectivity and activity. The effect of the addition of organic solvents to the biotransformation mixture was also determined. The results of the study suggested that SET1 is suitable for use in selected organo-aqueous media at specific ratios only. The functional group tolerance of the isolate with unprotected and protected β-aminonitriles, structural analogues of β-hydroxynitriles was also investigated with disappointingly poor isolated yields and selectivity obtained. The isolate was further evaluated with the α- aminonitrile phenylglycinonitrile generating acid in excellent yield and ee (>99 % (S) – isomer and 50 % yield). A series of pH studies with this substrate indicated pH 7 to be the optimum pH to avoid product and substrate degradation.
Three new bioactive natural products from the fungus Talaromyces assiutensis JTY2
Cai, Jin,Chen, Guang-Ying,Liao, Qi-Ying,Liao, Shan,Meng, Bo-Zhen,Tang, Min-Min,Yang, Xing,Zhou, Xue-Ming
, (2019/12/24)
A novel cyclopentenone derivative, talarocyclopenta A (1), a new phenolicethers derivative, talarocyclopenta B (2) and a new itaconic acid derivative, talarocyclopenta C (3) together with four known itaconic acid derivatives (4–7) were isolated from the Talaromyces assiutensis JTY2. Their structures were elucidated by the detailed analysis of comprehensive spectroscopic data. Among them, talarocyclopent (1) is the first represent an unusual type of cyclopentenone derivative, possessing a cyclopentenone unit, a 2-butanone unit and a 3-hydroxybutyric acid unit. All isolated compounds were evaluated for their anti-inflammatory and antibacterial activities. Compounds 1–4 showed inhibitory activities against the nitric oxide (NO) production induced by lipopolysaccharide in mouse macrophage RAW 264.7 cells in vitro. Compound 2 showed broad spectrum antibacterial against six terrestrial pathogenic bacteria.
Efficient synthesis of the ketone body ester (R)-3-hydroxybutyryl-(R)-3-hydroxybutyrate and its (S,S) enantiomer
Budin, Noah,Higgins, Erin,DiBernardo, Anthony,Raab, Cassidy,Li, Chun,Ulrich, Scott
, p. 560 - 564 (2018/07/25)
The ketone body ester (R)-3-hydroxybutyryl-(R)-3-hydroxybutyrate and its (S,S) enantiomer were prepared in a short, operationally simple synthetic sequence from racemic β-butyrolactone. Enantioselective hydrolysis of β-butyrolactone with immobilized Candida antarctica lipase-B (CAL-B) results in (R)-β-butyrolactone and (S)-β-hydroxybutyric acid, which are easily converted to (R) or (S)-ethyl-3-hydroxybutyrate and reduced to (R) or (S)-1,3 butanediol. Either enantiomer of ethyl-3-hydroxybutyrate and 1,3 butanediol are then coupled, again using CAL-B, to produce the ketone body ester product. This is an efficient, scalable, atom-economic, chromatography-free, and low cost synthetic method to produce the ketone body esters.
Functional characterization of salt-tolerant microbial esterase WDEst17 and its use in the generation of optically pure ethyl (R)-3-hydroxybutyrate
Wang, Yilong,Xu, Yongkai,Zhang, Yun,Sun, Aijun,Hu, Yunfeng
, p. 769 - 776 (2018/03/29)
The two enantiomers of ethyl 3-hydroxybutyrate are important intermediates for the synthesis of a great variety of valuable chiral drugs. The preparation of chiral drug intermediates through kinetic resolution reactions catalyzed by esterases/lipases has been demonstrated to be an efficient and environmentally friendly method. We previously functionally characterized microbial esterase PHE21 and used PHE21 as a biocatalyst to generate optically pure ethyl (S)-3-hydroxybutyrate. Herein, we also functionally characterized one novel salt-tolerant microbial esterase WDEst17 from the genome of Dactylosporangium aurantiacum subsp. Hamdenensis NRRL 18085. Esterase WDEst17 was further developed as an efficient biocatalyst to generate (R)-3-hydroxybutyrate, an important chiral drug intermediate, with the enantiomeric excess being 99% and the conversion rate being 65.05%, respectively, after process optimization. Notably, the enantio-selectivity of esterase WDEst17 was opposite than that of esterase PHE21. The identification of esterases WDEst17 and PHE21 through genome mining of microorganisms provides useful biocatalysts for the preparation of valuable chiral drug intermediates.
Stereochemical Consequences of Vinylpyruvate Hydratase-Catalyzed Reactions
Johnson, William H.,Stack, Tyler M. M.,Taylor, Stephanie M.,Burks, Elizabeth A.,Whitman, Christian P.
, p. 4055 - 4064 (2016/08/05)
A stereochemical analysis has been carried out on two vinylpyruvate hydratases (VPH), which convert 2-hydroxy-2,4-pentadienoate to 2-keto-4S-hydroxypentanoate in meta-fission pathways. Bacterial strains with this pathway can use aromatic compounds as sole sources of energy and carbon. The analysis was carried out using the 5-methyl and 5-chloro derivatives of 2-hydroxy-2,4-pentadienoate with the enzymes from Pseudomonas putida mt-2 (Pp) and Leptothrix cholodnii SP-6 (Lc). In both organisms, VPH is in a complex with the preceding enzyme in the pathway, 4-oxalocrotonate decarboxylase (4-OD). In D2O, a deuteron is incorporated stereospecifically at the C-3 and C-5 positions of product by both Pp and Lc enzymes. Accordingly, the complexes generate (3S,5S)-3,5-[di-D]-2-keto-4S-hydroxyhexanoate and (3S,5R)-3,5-[di-D]-2-keto-4R-hydroxy-5-chloropentanoate (4R and 5R due to a priority numbering change). The substitution at C-5 (CH3 or Cl) or the source of the enzyme (Pp or Lc) does not change the stereochemical outcome. One mechanism that can account for the results is the ketonization of the 5-substituted dienol to the α,β-unsaturated ketone (placing a deuteron at C-5 in D2O), followed by the conjugate addition of water (placing a deuteron at C-3). The stereochemical outcome for VPH (from Pp and Lc) is the same as that reported for a related enzyme, 2-oxo-hept-4-ene-1,7-dioate hydratase, from Escherichia coli C. The combined observations suggest similar mechanisms for these three enzymes that could possibly be common to this group of enzymes.
Acylated oleanane-type triterpene saponins from the flowers of Bellis perennis show anti-proliferative activities against human digestive tract carcinoma cell lines
Ninomiya, Kiyofumi,Motai, Chiaki,Nishida, Eriko,Kitagawa, Niichiro,Yoshihara, Kazuya,Hayakawa, Takao,Muraoka, Osamu,Li, Xuezheng,Nakamura, Seikou,Yoshikawa, Masayuki,Matsuda, Hisashi,Morikawa, Toshio
, p. 435 - 451 (2016/07/16)
Seven oleanane-type triterpene saponin bisdesmosides, perennisaponins N–T (1–7), were newly isolated from a methanol extract of daisy, the flowers of Bellis perennis L. (Asteraceae). The structures were determined based on chemical and physicochemical data and confirmed using previously isolated related compounds as references. The isolates, including 13 previously reported perennisaponins A–M (8–20), exhibited anti-proliferative activities against human digestive tract carcinoma HSC-2, HSC-4, and MKN-45 cells. Among them, perennisaponin O (2, IC50?=?11.2, 14.3, and 6.9?μM, respectively) showed relatively strong activities. The mechanism of action of 2 against HSC-2 was found to involve apoptotic cell death.
Absolute configurations of melanoxadin, MR-93A, melanoxazal, and MR-93B
He, Tian-Jun,Zhu, Shijun,Lu, Xiao-Wei,Wu, Yikang,Li, Yan
, p. 647 - 654 (2015/01/30)
Fungal metabolites melanoxadin, MR-93A, melanoxazal, and MR-93B were synthesized with the key stereogenic centers derived from commercially available chiral building blocks. The optically active synthetic products with well-defined absolute configurations provided authentic samples for the stereoisomers of these oxazole-containing natural products and thus allowed for unambiguous assignments of their relative and absolute configurations. The large discrepancies in the optical rotations between the natural and the pure synthetic samples are discussed. Some errors in the previously reported NMR signal assignments are also corrected.
Substrate evaluation of rhodococcus erythropolis SET1, a nitrile hydrolysing bacterium, demonstrating dual activity strongly dependent on nitrile sub-structure
Coady, Tracey M.,Coffey, Lee V.,O'Reilly, Catherine,Lennon, Claire M.
supporting information, p. 1108 - 1116 (2015/02/19)
Assessment of Rhodococcus erythropolis SET1, a novel nitrile hydrolysing bacterial isolate, has been undertaken with 34 nitriles, 33 chiral and 1 prochiral. These substrates consist primarily of β-hydroxy nitriles with varying alkyl and aryl groups at the β position and containing in several compounds different substituents α to the nitrile. In the case of β-hydroxy nitriles without substitution at the α position, acids were the major products obtained, along with recovered nitrile after biotransformation, as a result of suspected nitrilase activity of the isolate. Unexpectedly, amides were found to be the major hydrolysis product when the β-hydroxy nitriles possessed a vinyl group at this position. To probe this behaviour further, additional related substrates were evaluated containing electron-withdrawing groups at the α position, and amide was also observed upon biotransformation in the presence of SET1. Therefore this novel isolate has also demonstrated NHase activity with nitriles that appears to be substrate-dependent.
