Optically active 6-acetyloxy-2H-pyran-3(6H)-one obtained by lipase catalyzed transesterification and esterification

Heuvel, M. van den; Cuiper, Agnes D.; Deen, Hanneke van der; Kellogg, Richard M.; Feringa, Bernard

doi:10.1016/s0040-4039(97)00155-x

Cited by 53 publications

(21 citation statements)

References 20 publications

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“…Racemisation occurs spontaneously due to the inherently labile nature of these compounds (Scheme 11). 265 A similar observation was observed in the kinetic resolution of 8-amino-5,6,7,8-tetrahydroquinoline 17. A spontaneous DKR process was observed due to formation of an intermediate 18 in the reaction and reformation via an imine mechanism of the racemic hydroxy pyrrolone 17; moderate to good yields are reported (Scheme 11).…”

Section: Scheme 10supporting

confidence: 70%

Recent trends in whole cell and isolated enzymes in enantioselective synthesis

Milner¹,

Maguire²

2012

Arkivoc

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Modern synthetic organic chemistry has experienced an enormous growth in biocatalytic methodologies; enzymatic transformations and whole cell bioconversions have become generally accepted synthetic tools for asymmetric synthesis. This review details an overview of the latest achievements in biocatalytic methodologies for the synthesis of enantiopure compounds with a particular focus on chemoenzymatic synthesis in non-aqueous media, immobilisation technology and dynamic kinetic resolution. Furthermore, recent advances in ketoreductase technology and their applications are also presented.Keywords: Biocatalysis, kinetic and dynamic kinetic resolution, Baker's yeast, ketoreductases General IntroductionAsymmetric synthesis is the preferential formation of one stereoisomer of a chiral target compound to another; when scientists at GlaxoSmithKline, AstraZeneca and Pfizer 1 examined 128 syntheses from their companies, they found as many as half of the drug compounds made by their process research and development groups are not only chiral but also contain an average of two chiral centres each. 2In 2006 just 25 % were derived from the chiral pool and over 50 % employed chiral technologies. 1In order to meet regulatory requirements enantiomeric purities of 99.5 % were deemed necessary by the FDA. 3 This is one of the biggest challenges which face chemists today, primarily due to the recognition of the fact that different enantiomers of the same compound can interact differently in biological systems. As a consequence, the production of single enantiomers instead of racemic mixtures has become an important process in the pharmaceutical and agrochemical industry. Several routes can lead to the desired enantiomer including transition metal-, [4][5][6] organo-5,7-10 and bio-catalysis [11][12][13][14][15] and these have been thoroughly reviewed in the literature. 16,17 2. Biocatalysis IntroductionBiocatalysis involves the use of enzymes or whole cells (containing the desired enzyme or enzyme system) as catalysts for chemical reactions. A timeline of historic events in biocatalysis and biotechnology is outlined in Table 1. [18][19][20] Reviews and Accounts Novel methodologies for discovering industrial enzymes based on genomic sequencing and phage display (discussed further in Section 1.3), 21,22 as well as highly effective optimisation tools based on chemical, physical and molecular biology approaches, 23 have improved the access to biocatalysts, increased their stability, and radically broadened their specificity. 24This greater availability of catalysts with superior qualities including the use of new bioengineering tools contributed significantly to the development of new industrial processes. Biocatalytic methodologies for organic synthesis were outlined by Woodley et al. in three categories: established, emerging and expanding chemistries as depicted in Figure 1. 25 Enzyme classesBy the late 1950s it had become evident that the nomenclature of enzymes without any guiding authority, in a period when the...

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Section: Scheme 10supporting

confidence: 70%

Recent trends in whole cell and isolated enzymes in enantioselective synthesis

Milner¹,

Maguire²

2012

Arkivoc

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“…To increase both efficiency and overall yield, a dynamic kinetic asymmetric transformation (DYKAT) was considered for the acylation of the racemic lactol 2 a (Scheme ). Limited precedence existed for this transformation biocatalytically, and most reports achieved only low to moderate enantioselectivity 9. In fact, in our hands, screening of more than 100 enzymes led to either the undesired isomer [( R )‐ 3 a ]10 or ( S )‐ 3 a with low selectivity.…”

Section: Methodsmentioning

confidence: 77%

Scalable Synthesis of the Potent HIV Inhibitor BMS‐986001 by Non‐Enzymatic Dynamic Kinetic Asymmetric Transformation (DYKAT)

et al. 2015

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Described herein is the synthesis of BMS‐986001 by employing two novel organocatalytic transformations: 1) a highly selective pyranose to furanose ring tautomerization to access an advanced intermediate, and 2) an unprecedented small‐molecule‐mediated dynamic kinetic resolution to access a variety of enantiopure pyranones, one of which served as a versatile building block for the multigram, stereoselective, and chromatography‐free synthesis of BMS‐986001. The synthesis required five chemical transformations and resulted in a 44 % overall yield.

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“…Attempts to perform this reaction enantioselectively with rac ‐ 4 as the substrate and the chiral diphosphane 10 10 as ligand to Pd were unrewarding (∼30 % ee ). However, the use of 10 in combination with enantiomerically enriched ( S )‐ 4 (81 % ee ), which is easily prepared on a multigram scale by a lipase‐catalyzed dynamic resolution,11 served our purpose very well, and delivered the tricyclic ketone (−)‐ 5 in good yield and with excellent enantiomeric purity (96 % ee ) (Scheme ).…”

Section: Methodsmentioning

confidence: 99%