Predicting the enantiomeric selectivity of chymotrypsin. Homologous series of ester substances

Schwartz, Harold; Wu, Weh-Sai; Marr, Peter W.; Jones, J. Bryan

doi:10.1021/ja00484a049

Cited by 24 publications

(12 citation statements)

References 3 publications

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“…The original manufacturing route for the preparation of 3 is shown in Scheme . This process started with a classical resolution of rac- 5 with ( R )-phenylethylamine (PEA) to afford the ( S ) -5 /PEA salt . This was followed by a bromolactonization to give the corresponding optically pure lactone 6 (25% isolated yield from rac- 5 ).…”

Section: Resultsmentioning

confidence: 99%

“…5 This process started with a classical resolution of rac-5 with (R)-phenylethylamine (PEA) to afford the (S)-5/PEA salt. 6 This was followed by a bromolactonization to give the corresponding optically pure lactone 6 (25% isolated yield from rac-5). Then the lactone moiety in 6 was opened by dimethylamine (Me 2 NH) to form bromohydrin 7, which was converted to amino alcohol 9, with excellent regioselectivity, via the corresponding epoxide 8 following treatment with aqueous ammonia.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

“…(1S,4S,5S)-4-Bromo-6-oxabicyclo[3.2.1]octan-7-one (6). The previously prepared rac-6 wet cake (289.6 g) was charged to water (480 mL) and stirred at 30 °C.…”

Section: ■ Conclusionmentioning

confidence: 99%

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Development of an Efficient Manufacturing Process for a Key Intermediate in the Synthesis of Edoxaban

Michida

Ishikawa

Kaneda

et al. 2019

Org. Process Res. Dev.

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We report the development of a novel synthetic method to access a key intermediate in the synthesis of edoxaban. The main features of the new synthetic method are an improvement in the approach for the synthesis of a key chiral bromolactone, application of an interesting cyclization reaction utilizing neighboring group participation to construct a differentially protected 1,2-cis-diamine, and implementation of plug-flow reactor technology to enable the reaction of an unstable intermediate on multihundred kilogram scale. The overall yield for the preparation of edoxaban was significantly increased by implementing these changes and led to a more efficient and environmentally friendly manufacturing process.

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Section: Resultsmentioning

confidence: 99%

Section: ■ Results and Discussionmentioning

confidence: 99%

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Development of an Efficient Manufacturing Process for a Key Intermediate in the Synthesis of Edoxaban

Michida

Ishikawa

Kaneda

et al. 2019

Org. Process Res. Dev.

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“…Eistert synthesis of 4 from 1 [25], presumably with retention of configuration [30]. These compounds, along with those related to them (as, 5 and 6), all stand together in configuration.…”

Section: And Second By a M D T -mentioning

confidence: 99%

“…Comparisons of indane derivatives with openchain analogs in stereo-differentiating reductions and esterifications produced results that led to a refining of our understanding of the steric requirements of phenyl groups [ 18-2 11 -once configurational relationships had been established. The biological activity of indane-1 -carboxylic acid and other plant-growth stimulators is a function of absolute configuration [2] [22] [23] and chiral homologs and benzologs of this acid have been used in efforts to map out the size and shape of the active site for ester hydrolysis in chymotrypsin [24] [25]. Chiral indanols are formed in microbial reductions of indanones [26] [27], apparently in accord with Prelog's rule 1281.…”

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confidence: 99%

On the Absolute Configuration of Indane‐1‐carboxylic Acid

Brewster

1982

Helvetica Chimica Acta

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Summary Doubts that have recently been expressed [ l ] about the currently accepted (+ )-(R), (-)-(S)[2] absolute configuration of indane-1-carboxylic acid appear to be unwarranted. Our In the case of indanes the conformational relationship between the aromatic ring and a substituent on the five-membered ring is fairly well-defined'); this makes indanes valuable in areas of research where such relationships matter. As seen in Schemes l a , l b , and 2, indane-1-carboxylic acid (1) occupies a central position, rather like the hub of a wheel, in the pattern of configurational correlations in this series. It is important, then, to attribute neither more, nor less, certainty to the currently accepted configuration (+ )-(R), (-)-(S) [2] for 1 than the available evidence warrants. For this reason we cannot let certain statements made recently in this journal [ 11 stand unchallenged. Specifically, and to quote: 'It is shown unequivocally by chemical correlations and Raman optical activity spectra that the @)-configuration has to be attributed to (+ )-1-methylindane I )Some flexing of the saturated ring is possible but it seems likely that there is only one conformational energy minimum; the extent of noncoplananty could be a function of the steric requirements of the substituents. Puckering has been explicitly invoked by several workers in efforts to account for chiroptical phenomena that seem difficult to explain otherwise [7] [8] [9] [ 111 [ 151.

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Control of Regioselectivity in the Transition‐Metal‐Catalysed Conjugate Additions of Alkylaluminium Compounds and Methyltitanium Ate Complexes to Androsta‐1,4‐diene‐3,17‐dione

Westermann¹,

Neh²,

Nickisch³

1996

Chem. Ber.

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By a variation of the nature of the reagent system conjugate addition to the cross‐conjugated steroidal dienone 1 occurs selectively either at C‐1 or at the sterically hindered C‐5. With Me3Al or Me4AlLi in the presence of catalytic amounts of Cu1 salts, a high regioselectivity (up to 97:3) in favour of position 1 is achieved. Application of ate complexes of aluminium and titanium in the presence of Ni(acac)2 as catalyst, however, leads to a reversal of the regioselectivity in favour of position 5 (up to 11:89). Aluminium and titanium ate complexes are efficient reagents in the Ni(acac)2‐catalysed conjugate addition to sterically hindered enones.

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Predicting the enantiomeric selectivity of chymotrypsin. Homologous series of ester substances

Cited by 24 publications

References 3 publications

Development of an Efficient Manufacturing Process for a Key Intermediate in the Synthesis of Edoxaban

Development of an Efficient Manufacturing Process for a Key Intermediate in the Synthesis of Edoxaban

On the Absolute Configuration of Indane‐1‐carboxylic Acid

Control of Regioselectivity in the Transition‐Metal‐Catalysed Conjugate Additions of Alkylaluminium Compounds and Methyltitanium Ate Complexes to Androsta‐1,4‐diene‐3,17‐dione

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