Paul Spurr - Academia.edu (original) (raw)
Papers by Paul Spurr
Publication View. 33189266. Derivatives of iceane : a study in molecular architecture / by Paul R... more Publication View. 33189266. Derivatives of iceane : a study in molecular architecture / by Paul Raymond Spurr (1982). Spurr, Paul Raymond. Abstract. Typescript (photocopy). viii, 182 leaves : ill. ; 30 cm.. Title page, contents and abstract only. ...
ChemInform, Sep 8, 1987
ChemInform Abstract (1.1.1.1)Pagodane (Ia) and its dione (Ib) are transformed by some reaction se... more ChemInform Abstract (1.1.1.1)Pagodane (Ia) and its dione (Ib) are transformed by some reaction sequences alluding to different syntheses of dodecahedrane. Bromination with Br2 in a large excess gives dibromides (II) which on warming or irradiation lose bromine to regenerate (I). Conventional reduction of the dibromides (II) then leads to the dienes (III) (regenerating (I) under acetone-sensitized excitation) which add bromine regiospecifically to give back the dibromides (II). The hyperstable dienes (III) and enes (IV) cannot be reduced to the saturated compounds even under drastic conditions (in the presence of Pd, Pt, or Rh), only the monoenes (IV) can be achieved. When heated for a short time, the enes (IV) rearrange to (V). Further reactions of (IIIa), (IIIb) and (IVa), (IVb) lead to products as shown inthe scheme-here only described for the hydrocarbons (IIIa) and (IVa) for reasons of simplicity; the diones (IIIb) and (IVb), however, give analogous products (and yields) in each case. Molecular data from MM2 calculations (C,C and H,H distances, formation enthalpies, strain energies) are given for the sequence (Ia), (IIIa), (IVa), its saturated counterpart, a didehydro derivative (with a new C-Cbond) of the latter, and dodecahedrane (an isomer of (Ia)).
ChemInform, Aug 21, 2010
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was e... more ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform, Nov 24, 1987
The class of "pagodanes" such as (X) constitutes a novel series of undecacyclic, strain... more The class of "pagodanes" such as (X) constitutes a novel series of undecacyclic, strained and chemically versatile carbon frameworks.
![Research paper thumbnail of ChemInform Abstract: Photochemical Transformations. Part 68. [6 + 6]-Benzo/Benzo-Photocycloaddition Reactions](https://attachments.academia-assets.com/109204243/thumbnails/1.jpg)
](Chemischer Informationsdienst, Sep 2, 1986
ChemInform Abstract Die Bestrahlung von Nitroalkanen wie (I) in z.B. Cyclohexan führt zu den Capr... more ChemInform Abstract Die Bestrahlung von Nitroalkanen wie (I) in z.B. Cyclohexan führt zu den Caprolactamen (II), daneben entstehen Amide wie z.B. N-Cyclohexyl-acetamid im Falle R =Äthyl oder N-Cyclohexyl-und N-Cyclohexyl-N-methyl-acetamid im FalleR =Propyl-(2). erner entstehen Cyclohexanon, Cyclohexanol und Nitrocyclohexan als Nebenprodukte. Anhand des ermittelten Produktspektrums werden Mechanismen der Photoreaktion diskutiert, die vermutlichüber Radikale und Oxaziridine verläuft.
Tetrahedron Letters, 1986
Abstract Cyclobutane-formation between “face-to-race” oriented benzenoid chromophoric units has b... more Abstract Cyclobutane-formation between “face-to-race” oriented benzenoid chromophoric units has been observed in 1,6-diene- (B) (1b–d/4a–d), not, however, in 1,5-diene-derived (C) (7a–c) skeletons.
Nature Chemistry, 2016
The use of transaminases to access pharmaceutically relevant chiral amines is an attractive alter... more The use of transaminases to access pharmaceutically relevant chiral amines is an attractive alternative to transition-metal-catalysed asymmetric chemical synthesis. However, one major challenge is their limited substrate scope. Here we report the creation of highly active and stereoselective transaminases starting from fold class I. The transaminases were developed by extensive protein engineering followed by optimization of the identified motif. The resulting enzymes exhibited up to 8,900-fold higher activity than the starting scaffold and are highly stereoselective (up to >99.9% enantiomeric excess) in the asymmetric synthesis of a set of chiral amines bearing bulky substituents. These enzymes should therefore be suitable for use in the synthesis of a wide array of potential intermediates for pharmaceuticals. We also show that the motif can be engineered into other protein scaffolds with sequence identities as low as 70%, and as such should have a broad impact in the field of biocatalytic synthesis and enzyme engineering.
Nature Chemistry, 2016
The use of transaminases to access pharmaceutically relevant chiral amines is an attractive alter... more The use of transaminases to access pharmaceutically relevant chiral amines is an attractive alternative to transition-metal-catalysed asymmetric chemical synthesis. However, one major challenge is their limited substrate scope. Here we report the creation of highly active and stereoselective transaminases starting from fold class I. The transaminases were developed by extensive protein engineering followed by optimization of the identified motif. The resulting enzymes exhibited up to 8,900-fold higher activity than the starting scaffold and are highly stereoselective (up to >99.9% enantiomeric excess) in the asymmetric synthesis of a set of chiral amines bearing bulky substituents. These enzymes should therefore be suitable for use in the synthesis of a wide array of potential intermediates for pharmaceuticals. We also show that the motif can be engineered into other protein scaffolds with sequence identities as low as 70%, and as such should have a broad impact in the field of biocatalytic synthesis and enzyme engineering.
ACS Medicinal Chemistry Letters, 2012
La presente invention concerne un procede de production de composes correspondant a la formule ge... more La presente invention concerne un procede de production de composes correspondant a la formule generale (I), dans laquelle: R2a, R2b representent, independamment l'un de l'autre, hydrogene, halogene, alcoxy inferieur, cyano, -COOH, alcoxycarbonyle inferieur ou alkyle inferieur, eventuellement substitue par halogene; et R3a, R3b representent, independamment l'un de l'autre, hydrogene, alkyle inferieur, cycloalkyle inferieur ou bien, ensemble, -(CH?2?)n- ou n = 2, 3 ou 5. Lesdits composes correspondant a la formule (I) constituent des intermediaires appreciables pour la preparation de composes therapeutiquement actifs tels que le 2-(3-5-bis-trifluoromethylphenyl)-N-methyl-N-(6-morpholin-4-yl-4-yl-4-o-tolylpyridin-3-yl)-isoburyramide et le 2-(3-5-bis-trifluoromethylphenyl)-N-methyl-N-(2-morpholin-4-yl-4-o-tolyloxy-pyrimidin-5-yl)-isobutyramide.
A process for the manufacture of compounds of formula I wherein A together with the two carbon at... more A process for the manufacture of compounds of formula I wherein A together with the two carbon atoms denoted as {AL} and {BE} REPRESENTS ONE OF THE GROUPS R {SUP, 1} represents cyano or a group of the formula COOR {SUP, 4}, {R SUP, 2} represents hydrogen, R SUP {3} represents alkyl LOW, OR SUP {2} {SUP YR, 3} together are di- or trimethylene GROUP, R {SUP, 4} LOW represents alkyl or benzyl; YR {SUP, 5}, R {SUP, 6} each signify hydrogen, halogen, trifluoromethyl, lower alkoxy or nitro and the carbon atom denoted by {GA} HAVING CONFIGURATION S when R {SUP, 2} DIFFERENT FROM HYDROGEN; Which process comprises reacting a compound of the formula wherein A, R {SUP, 2} YR {SUP, 3} have the meaning given above YX represents a halogen atom, in the presence of base with a compound of formula WHERE R SUP {7} is alkyl or cycloalkyl YR LOW SUP {1} has the meaning given above.
The present invention concerns a process for the preparation of derivatives of 3 - AMINO - pyrrol... more The present invention concerns a process for the preparation of derivatives of 3 - AMINO - pyrrolidine represented by formula (I): wherein R 1 represents hydrogen, alkyl, cycloalkyl, alkenyl, aryl or a protecting group NOT ME; YR 3 R 2 each represent, IN dependently, hydrogen, alkyl, cycloalkyl, alkenyl or aryl. Said preparation is carried out by converting a compound represented by formula (II): wherein X represents a hydroxyl group protected; IN THE PRESENCE OF A FORMULA primary amine R 1 NH 2 IN pyrrolidine derivative represented by formula (III): where, XYR 1 REPRESENT than previously mentioned. Said compound is further reacted IN PRESENCE SUP R, 2 R 3 NH and under pressure. The invention also relates to the use of this PROCESS FOR PRODUCING DERIVATIVES vinylpyrrolidone - cephalosporin.
Organic & biomolecular chemistry, Jan 2, 2016
Application of amine transaminases (ATAs) for stereoselective amination of prochiral ketones repr... more Application of amine transaminases (ATAs) for stereoselective amination of prochiral ketones represents an environmentally benign and economically attractive alternative to transition metal catalyzed asymmetric synthesis. However, the restrictive substrate scope has limited the conversion typically to non-sterically demanding scaffolds. Recently, we reported on the identification and design of fold class I ATAs that effect a highly selective asymmetric synthesis of a set of chiral aromatic bulky amines from the corresponding ketone precursors in high yield. However, for the specific amine synthetic approach extension targeted here, the selective formation of an exo- vs. endo-isomer, these biocatalysts required additional refinement. The chosen substrate (exo-3-amino-8-aza-bicyclo[3.2.1]oct-8-yl-phenyl-methanone), apart from its pharmacological relevance, is a demanding target for ATAs as the bridged bicyclic ring provides substantial steric challenges. Protein engineering combining ...
Chembiochem : a European journal of chemical biology, Jun 23, 2017
Amine transaminase (ATA) catalysing stereoselective amination of prochiral ketones is an attracti... more Amine transaminase (ATA) catalysing stereoselective amination of prochiral ketones is an attractive alternative to transition metal catalysis. As wild-type ATAs accept only non-sterically hindered ketones, efforts to widen the substrate scope to more challenging targets are of general interest. We recently designed ATAs to accept aromatic and thus planar bulky amines, via a sequenced based motif that supports the identification of novel enzymes. However, these variants were not active against 2,2-dimethyl-1-phenyl-propan-1-one, which carries a spatially bulky tert-butyl substituent adjacent to the carbonyl function. Here, we report on a differentiated solution for this type of substrate. The evolved ATAs can perform asymmetric synthesis of the respective (R)-amine with high conversions using either alanine or isopropylamine as amine donors.
Publication View. 33189266. Derivatives of iceane : a study in molecular architecture / by Paul R... more Publication View. 33189266. Derivatives of iceane : a study in molecular architecture / by Paul Raymond Spurr (1982). Spurr, Paul Raymond. Abstract. Typescript (photocopy). viii, 182 leaves : ill. ; 30 cm.. Title page, contents and abstract only. ...
ChemInform, Sep 8, 1987
ChemInform Abstract (1.1.1.1)Pagodane (Ia) and its dione (Ib) are transformed by some reaction se... more ChemInform Abstract (1.1.1.1)Pagodane (Ia) and its dione (Ib) are transformed by some reaction sequences alluding to different syntheses of dodecahedrane. Bromination with Br2 in a large excess gives dibromides (II) which on warming or irradiation lose bromine to regenerate (I). Conventional reduction of the dibromides (II) then leads to the dienes (III) (regenerating (I) under acetone-sensitized excitation) which add bromine regiospecifically to give back the dibromides (II). The hyperstable dienes (III) and enes (IV) cannot be reduced to the saturated compounds even under drastic conditions (in the presence of Pd, Pt, or Rh), only the monoenes (IV) can be achieved. When heated for a short time, the enes (IV) rearrange to (V). Further reactions of (IIIa), (IIIb) and (IVa), (IVb) lead to products as shown inthe scheme-here only described for the hydrocarbons (IIIa) and (IVa) for reasons of simplicity; the diones (IIIb) and (IVb), however, give analogous products (and yields) in each case. Molecular data from MM2 calculations (C,C and H,H distances, formation enthalpies, strain energies) are given for the sequence (Ia), (IIIa), (IVa), its saturated counterpart, a didehydro derivative (with a new C-Cbond) of the latter, and dodecahedrane (an isomer of (Ia)).
ChemInform, Aug 21, 2010
ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was e... more ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
ChemInform, Nov 24, 1987
The class of "pagodanes" such as (X) constitutes a novel series of undecacyclic, strain... more The class of "pagodanes" such as (X) constitutes a novel series of undecacyclic, strained and chemically versatile carbon frameworks.
Chemischer Informationsdienst, Sep 2, 1986
ChemInform Abstract Die Bestrahlung von Nitroalkanen wie (I) in z.B. Cyclohexan führt zu den Capr... more ChemInform Abstract Die Bestrahlung von Nitroalkanen wie (I) in z.B. Cyclohexan führt zu den Caprolactamen (II), daneben entstehen Amide wie z.B. N-Cyclohexyl-acetamid im Falle R =Äthyl oder N-Cyclohexyl-und N-Cyclohexyl-N-methyl-acetamid im FalleR =Propyl-(2). erner entstehen Cyclohexanon, Cyclohexanol und Nitrocyclohexan als Nebenprodukte. Anhand des ermittelten Produktspektrums werden Mechanismen der Photoreaktion diskutiert, die vermutlichüber Radikale und Oxaziridine verläuft.
Tetrahedron Letters, 1986
Abstract Cyclobutane-formation between “face-to-race” oriented benzenoid chromophoric units has b... more Abstract Cyclobutane-formation between “face-to-race” oriented benzenoid chromophoric units has been observed in 1,6-diene- (B) (1b–d/4a–d), not, however, in 1,5-diene-derived (C) (7a–c) skeletons.
Nature Chemistry, 2016
The use of transaminases to access pharmaceutically relevant chiral amines is an attractive alter... more The use of transaminases to access pharmaceutically relevant chiral amines is an attractive alternative to transition-metal-catalysed asymmetric chemical synthesis. However, one major challenge is their limited substrate scope. Here we report the creation of highly active and stereoselective transaminases starting from fold class I. The transaminases were developed by extensive protein engineering followed by optimization of the identified motif. The resulting enzymes exhibited up to 8,900-fold higher activity than the starting scaffold and are highly stereoselective (up to >99.9% enantiomeric excess) in the asymmetric synthesis of a set of chiral amines bearing bulky substituents. These enzymes should therefore be suitable for use in the synthesis of a wide array of potential intermediates for pharmaceuticals. We also show that the motif can be engineered into other protein scaffolds with sequence identities as low as 70%, and as such should have a broad impact in the field of biocatalytic synthesis and enzyme engineering.
Nature Chemistry, 2016
The use of transaminases to access pharmaceutically relevant chiral amines is an attractive alter... more The use of transaminases to access pharmaceutically relevant chiral amines is an attractive alternative to transition-metal-catalysed asymmetric chemical synthesis. However, one major challenge is their limited substrate scope. Here we report the creation of highly active and stereoselective transaminases starting from fold class I. The transaminases were developed by extensive protein engineering followed by optimization of the identified motif. The resulting enzymes exhibited up to 8,900-fold higher activity than the starting scaffold and are highly stereoselective (up to >99.9% enantiomeric excess) in the asymmetric synthesis of a set of chiral amines bearing bulky substituents. These enzymes should therefore be suitable for use in the synthesis of a wide array of potential intermediates for pharmaceuticals. We also show that the motif can be engineered into other protein scaffolds with sequence identities as low as 70%, and as such should have a broad impact in the field of biocatalytic synthesis and enzyme engineering.
ACS Medicinal Chemistry Letters, 2012
La presente invention concerne un procede de production de composes correspondant a la formule ge... more La presente invention concerne un procede de production de composes correspondant a la formule generale (I), dans laquelle: R2a, R2b representent, independamment l'un de l'autre, hydrogene, halogene, alcoxy inferieur, cyano, -COOH, alcoxycarbonyle inferieur ou alkyle inferieur, eventuellement substitue par halogene; et R3a, R3b representent, independamment l'un de l'autre, hydrogene, alkyle inferieur, cycloalkyle inferieur ou bien, ensemble, -(CH?2?)n- ou n = 2, 3 ou 5. Lesdits composes correspondant a la formule (I) constituent des intermediaires appreciables pour la preparation de composes therapeutiquement actifs tels que le 2-(3-5-bis-trifluoromethylphenyl)-N-methyl-N-(6-morpholin-4-yl-4-yl-4-o-tolylpyridin-3-yl)-isoburyramide et le 2-(3-5-bis-trifluoromethylphenyl)-N-methyl-N-(2-morpholin-4-yl-4-o-tolyloxy-pyrimidin-5-yl)-isobutyramide.
A process for the manufacture of compounds of formula I wherein A together with the two carbon at... more A process for the manufacture of compounds of formula I wherein A together with the two carbon atoms denoted as {AL} and {BE} REPRESENTS ONE OF THE GROUPS R {SUP, 1} represents cyano or a group of the formula COOR {SUP, 4}, {R SUP, 2} represents hydrogen, R SUP {3} represents alkyl LOW, OR SUP {2} {SUP YR, 3} together are di- or trimethylene GROUP, R {SUP, 4} LOW represents alkyl or benzyl; YR {SUP, 5}, R {SUP, 6} each signify hydrogen, halogen, trifluoromethyl, lower alkoxy or nitro and the carbon atom denoted by {GA} HAVING CONFIGURATION S when R {SUP, 2} DIFFERENT FROM HYDROGEN; Which process comprises reacting a compound of the formula wherein A, R {SUP, 2} YR {SUP, 3} have the meaning given above YX represents a halogen atom, in the presence of base with a compound of formula WHERE R SUP {7} is alkyl or cycloalkyl YR LOW SUP {1} has the meaning given above.
The present invention concerns a process for the preparation of derivatives of 3 - AMINO - pyrrol... more The present invention concerns a process for the preparation of derivatives of 3 - AMINO - pyrrolidine represented by formula (I): wherein R 1 represents hydrogen, alkyl, cycloalkyl, alkenyl, aryl or a protecting group NOT ME; YR 3 R 2 each represent, IN dependently, hydrogen, alkyl, cycloalkyl, alkenyl or aryl. Said preparation is carried out by converting a compound represented by formula (II): wherein X represents a hydroxyl group protected; IN THE PRESENCE OF A FORMULA primary amine R 1 NH 2 IN pyrrolidine derivative represented by formula (III): where, XYR 1 REPRESENT than previously mentioned. Said compound is further reacted IN PRESENCE SUP R, 2 R 3 NH and under pressure. The invention also relates to the use of this PROCESS FOR PRODUCING DERIVATIVES vinylpyrrolidone - cephalosporin.
Organic & biomolecular chemistry, Jan 2, 2016
Application of amine transaminases (ATAs) for stereoselective amination of prochiral ketones repr... more Application of amine transaminases (ATAs) for stereoselective amination of prochiral ketones represents an environmentally benign and economically attractive alternative to transition metal catalyzed asymmetric synthesis. However, the restrictive substrate scope has limited the conversion typically to non-sterically demanding scaffolds. Recently, we reported on the identification and design of fold class I ATAs that effect a highly selective asymmetric synthesis of a set of chiral aromatic bulky amines from the corresponding ketone precursors in high yield. However, for the specific amine synthetic approach extension targeted here, the selective formation of an exo- vs. endo-isomer, these biocatalysts required additional refinement. The chosen substrate (exo-3-amino-8-aza-bicyclo[3.2.1]oct-8-yl-phenyl-methanone), apart from its pharmacological relevance, is a demanding target for ATAs as the bridged bicyclic ring provides substantial steric challenges. Protein engineering combining ...
Chembiochem : a European journal of chemical biology, Jun 23, 2017
Amine transaminase (ATA) catalysing stereoselective amination of prochiral ketones is an attracti... more Amine transaminase (ATA) catalysing stereoselective amination of prochiral ketones is an attractive alternative to transition metal catalysis. As wild-type ATAs accept only non-sterically hindered ketones, efforts to widen the substrate scope to more challenging targets are of general interest. We recently designed ATAs to accept aromatic and thus planar bulky amines, via a sequenced based motif that supports the identification of novel enzymes. However, these variants were not active against 2,2-dimethyl-1-phenyl-propan-1-one, which carries a spatially bulky tert-butyl substituent adjacent to the carbonyl function. Here, we report on a differentiated solution for this type of substrate. The evolved ATAs can perform asymmetric synthesis of the respective (R)-amine with high conversions using either alanine or isopropylamine as amine donors.