hans Bieraugel - Academia.edu (original) (raw)

Papers by hans Bieraugel

Organic and Biomolecular Chemistry, 2003

A new method to cyclise peptides is reported based on insertion of a salicylaldehyde derived pinc... more A new method to cyclise peptides is reported based on insertion of a salicylaldehyde derived pincer auxiliary in the linear precursor sequence. H-betaAla-Phe-OH and H-Phe-betaAla-OH were chosen as representative model peptides.

Journal of Physical Chemistry B, Oct 17, 2014

We report on experimental high-resolution spectroscopic studies in combination with ab initio com... more We report on experimental high-resolution spectroscopic studies in combination with ab initio computational studies that investigate the excited-state dynamics of methyl-4-hydroxycinnamate thioester and (5-hydroxyindan-(1E)-ylidene)acetic acid, derivatives of the photoactive yellow protein (PYP) chromophore. These studies aim to elucidate (a) how the thioester moiety influences the photophysics and photochemistry of the p-coumaric acid chromophore and (b) to what extent rotation of the single bond adjacent to the phenyl ring is involved in the decay dynamics of the electronically excited states. The experimental studies show that sulfur substitution leads to broad, unstructured excitation spectra that contrast sharply with the well-resolved spectra of compounds with an oxygen-based ester. Furthermore, internal conversion to the lower-lying nπ* state is absent. The absence of this decay channel is rationalized by quantum-chemical calculations that reveal that in the nπ* state of the thio compounds the molecule exhibits a large out-of-plane "kink" at the sulfur atom. Franck-Condon simulations of the excitation spectra of the V(ππ*) state highlight the activity of various vibrational modes in the neutral chromophore and indicate that upon sulfur substitution internal conversion to the ground state occurs at a significantly higher rate. The similarities observed in the excitation spectra and decay dynamics of the locked and unlocked compounds suggest that in the present experiments single-bond torsion does not show up prominently. The conclusion that for the isolated molecule double-bond torsion is dominating the excited-state dynamics is tentatively confirmed by the quantum-chemical calculations.

Tetrahedron Letters, 1974

Pure and Applied Chemistry, 1994

Progress towards the synthesis of the marine alkaloid manzamine A is described. The synthesis of ... more Progress towards the synthesis of the marine alkaloid manzamine A is described. The synthesis of the ABCD ring system has been achieved, with the macrocyclic D ring being formed by an olefin metathesis cyclization. Additionally, a chiral ABC tricyclic intermediate has been converted into the ring D-nor manzamine A skeleton. The alkaloid manzamine A (l), isolated from the sea sponges Haliclona sp.,latbXestopongia sp.lC and Pellina sp.,2 found in the waters of the Okinawa Sea, exhibits significant antileukemic and antimicrobial activity. The compound possesses an unusual nitrogen-containing pentacyclic fused ring system (ABCDE), bearing a pendant P-carboline moiety. An ingenious hypothetical scheme for the biosynthesis of manzamine A has been proposed by Baldwin and Whitehead.3 According to this scheme, the P-carboline nucleus is completed on the ABCDE template in the last stages of the biosynthesis. The latter aspect has recently received support from the finding that an ABCDE aldehyde, called ircinal A, a constituent of Zrcinia sp., is chemically convertible into manzamine A.4 C02Me

Pure and Applied Chemistry, 1996

The total synthesis of the ABCDE ring system of manzamine A, with the correct absolute stereochem... more The total synthesis of the ABCDE ring system of manzamine A, with the correct absolute stereochemistry at the chiral centers, is described. Key steps in the synthetic route are the formation of both the eight-and the thirteen-membered rings by an olefin metathesis cyclization reaction.

Organic Letters, Jul 18, 2002

A novel method for the synthesis of medium-sized lactams based on an auxiliary-mediated combined ... more A novel method for the synthesis of medium-sized lactams based on an auxiliary-mediated combined tethered/templated strategy is presented. Cyclization by a tethered ring-closing metathesis reaction was followed by a templated transannular aminolysis reaction to give seven-to ten-membered lactams in good yields. Scheme 1. Retrosynthetic Outline of the Combined Tethered/ Templated Approach toward Lactams

Heterocycles, 1988

Obtention de tetrahydro hydroxy-8 ou oxo-8 isoquinoleinetricarboxylates-5,5,7 de triethyle et de ... more Obtention de tetrahydro hydroxy-8 ou oxo-8 isoquinoleinetricarboxylates-5,5,7 de triethyle et de methyl-7 oxo-8 tetrahydro isoquinoleinedicarboxylates-5,7 de diethyle

Chemistry: A European Journal, Nov 7, 2013

ABSTRACT Smooth operation: C-terminal peptide activation with full stereointegrity was accomplish... more ABSTRACT Smooth operation: C-terminal peptide activation with full stereointegrity was accomplished using a copper(II)-mediated coupling reaction of carboxylic acids with arylboroxines (see scheme, NCL = native chemical ligation, Boc = tert-butoxycarbonyl). This method allows epimerization-free activation and ligation of peptides with racemization-prone phenylglycine at the C terminus.

Tetrahedron, 1983

Abstract 2-Substituted 1-tosyl-3,4,4-trimethylimidazolidines prepared by the addition of anions t... more Abstract 2-Substituted 1-tosyl-3,4,4-trimethylimidazolidines prepared by the addition of anions to 1-tosyl-3,4,4-trimethyl-2-imidazolinium iodide 1, react with tryptamine in the presence of acetic acid to give 1-substituted β-carboline derivatives. The salt 1 reacts with anions of 2-[2-(1,3-dithianyl)]benzoates 4a-c to give the corresponding imidazolidines 5a, 5b and 5c, respectively. These transfer the substituted fragment to tryptamine to give pentacyclic products corresponding to the yohimbane skeleton. The product from 5c yields, after reduction of both the amide and the dithiane function, the precursor of epi- and allo-yohimbanes.

Recueil des Travaux Chimiques des Pays-Bas, Sep 2, 2010

Dienamines derived from 8a-methyl-1,6-dioxo-1,2,3,4,6,7,8,8a-octahydronaphthalene (2) and (+)(7aS... more Dienamines derived from 8a-methyl-1,6-dioxo-1,2,3,4,6,7,8,8a-octahydronaphthalene (2) and (+)(7aS)-7a-methyl-2,3,5,6,7,8-hexahydro-1,5(lm-indandione (12) react with 3-bromo-243-methoxypheny1)propene (3) to give the corresponding 5and 4-substituted alkylation products 8 and 14a, respectively. 8 can be directly cyclized to 6-methyl-D-homoequilenin derivative 9 by heating with acid. While 14a can be similarly converted into the corresponding equilenin methyl ether (15a), better yields in the cyclization step are achieved by initial reduction of the 5-ring ketone function and acetylation of the resulting alcohol. The latter sequence of reactions with 14a, derived from 12, gives optically active 17~-acetoxy-6-methylestra-1,3,5,7,9,14-haxaen-3-ol methyl ether (15b), which can serve as an central intermediate for optically active steroids. ' (a) H .

Journal of the Chemical Society, 1979

Suitably substituted imidazolidinium salts serve as N5N10-methenyltetrahydrofolate models in term... more Suitably substituted imidazolidinium salts serve as N5N10-methenyltetrahydrofolate models in terms of their ability to transfer a formyl equivalent to a variety of mono- and bi-functional nucleophiles.

Heterocyclic Communications, 1995

The 8-membered ring Ε has been introduced onto a strategically functionalized chiral pyrrolo[2,3-... more The 8-membered ring Ε has been introduced onto a strategically functionalized chiral pyrrolo[2,3-/]isoquinoline derivative by a combination of a Wittig coupling and amide cyclization. The resulting tetracyclic structure has been converted to the ABCE-ß-carboline ring system of manzamine A. The novel structure and significant biological activity of manzamine A 1-an alkaloid isolated from sea sponges found in the Okinawan waters (1)-has drawn keen attention in connection with its biosynthetic origin (2) and chemical synthesis (3). In a retrosynthetic analysis of the alkaloid, we, and a number of other groups, have recognized that the ABC ring system of manzamine A constitutes a core structure upon which the remaining rings of the target compound may be elaborated. In this context, we reported the first synthesis of the strategically functionalized chiral pyrrolo[2,3-/]isoquinoline intermediate 2 (3d). We now present the elaboration of 2 to the ABCE-ß-carboline ring system of manzamine A.

Tetrahedron, 1983

Abstract Carboxylate esters react with 1,2-diaminoethanes to yield imidazolines, which upon conse... more Abstract Carboxylate esters react with 1,2-diaminoethanes to yield imidazolines, which upon consecutive reaction with acetic anhydride or tosyl chloride and methyl iodide give imidazolinium salts that serve as models of N5,N10-(CH+)-tetrahydrofolate (THF) coenzymes (7a, b and 18a, b). Reduction of the latter salts with sodium borohydride or reaction with anions (R−) give the corresponding 5,10-[CH(H,R)]-THF models. Mono- and bifunctional nucleophiles react with 18a, b to yield carbon-transfer products 6-Alkylamino-1,3-dimethyluracils react with 1 tosyl-3,4,4-trimethylimidazolidine (the reduction product of 18b), in the presence of acetic acid, to form carbon transfer products via a mechanism which bears close analogy to the mechanism of action of thymidylate synthetase.

Recueil des Travaux Chimiques des Pays-Bas, Sep 2, 2010

Under conditions of acid-catalyzed cyclization, migration of the double bond from C-C=CH, to the ... more Under conditions of acid-catalyzed cyclization, migration of the double bond from C-C=CH, to the C=C-CH, system accounts for 20% of the starting acetate.

Angewandte Chemie, Sep 22, 2003

Organic and Biomolecular Chemistry, 2022

Phenol ester activated dipeptides that are reluctant to ring-close have been cyclised with the ai... more Phenol ester activated dipeptides that are reluctant to ring-close have been cyclised with the aid of sterically shielding metallo-porphyrins avoiding unwanted intermolecular reactions. The binding of ZnTPP to the dipyridine-functionalised activating phenolic ester was studied by NMR titrations and modelling. Staudinger-mediated cyclisations in the presence of ZnTPP increased the yield of the cyclic dipeptide from 16% to 40%. † Electronic supplementary information (ESI) available. See

Recueil des Travaux Chimiques des Pays-Bas, 1976

H. Bieraugel et al. j Functionalized enamines-Part X X I V HCL The usual work up afforded 5, b.p.... more H. Bieraugel et al. j Functionalized enamines-Part X X I V HCL The usual work up afforded 5, b.p. 107-110~/0.02 mm, np 1.6710 in 76% yield 'H-NMR spectrum: 6 5.57 (s,-CH=); 6 2.42 and 2.44 (s, I =C-SCH,); 6 2.34(~, =C-SCH,). IR: 2140 cm-' (C=C, m). b. Formation of l.1.4-tris(methylthio)-l-buten-3-yne (5) (second To a suspension of 0.075 mole of sodamide (prepared from sodium and liquid ammonia under the catalytic influence of ferric nitrate) in 250 ml of liquid ammonia were added 8.8 g (0.05 mole) of 23bis(methy1thio)thiophene After stirring for 1 hour the mixture was cooled to-50" and 12 g (0.085 mole) of methyl iodide were added. The ammonia was evaporated by placing the flask in a water bath at 40°. The usual work up gave 5 in 8004 yield. method) c. Formation of 2-methylS -(methylthio)thiophene (6) A solution of 8.8 g (0.05 mole) of 2,5-bis(methylthio)thiophene in 250 ml of THF and 50 ml of HMPT was cooled to-65". To this mixture a solution of 0.09 mole of butyllithium in 45 ml of hexane was added drop by drop at-65O. After the addition the reaction mixture was kept at-400 for 15 minutes and subsequently 14.2 g (0.10 mole) of methyl iodide' were added over 30 minutes with cooling at-60". The mixture was then poured into ice-water. 5-Methyl-2-(methylthio)thiophene (6) (compare 9), b.p. 90-920/ 20 mm, nAo 1.5708, was obtained in 77-80% yield.

Organic and Biomolecular Chemistry, 2003

A new method to cyclise peptides is reported based on insertion of a salicylaldehyde derived pinc... more A new method to cyclise peptides is reported based on insertion of a salicylaldehyde derived pincer auxiliary in the linear precursor sequence. H-betaAla-Phe-OH and H-Phe-betaAla-OH were chosen as representative model peptides.

Journal of Physical Chemistry B, Oct 17, 2014

We report on experimental high-resolution spectroscopic studies in combination with ab initio com... more We report on experimental high-resolution spectroscopic studies in combination with ab initio computational studies that investigate the excited-state dynamics of methyl-4-hydroxycinnamate thioester and (5-hydroxyindan-(1E)-ylidene)acetic acid, derivatives of the photoactive yellow protein (PYP) chromophore. These studies aim to elucidate (a) how the thioester moiety influences the photophysics and photochemistry of the p-coumaric acid chromophore and (b) to what extent rotation of the single bond adjacent to the phenyl ring is involved in the decay dynamics of the electronically excited states. The experimental studies show that sulfur substitution leads to broad, unstructured excitation spectra that contrast sharply with the well-resolved spectra of compounds with an oxygen-based ester. Furthermore, internal conversion to the lower-lying nπ* state is absent. The absence of this decay channel is rationalized by quantum-chemical calculations that reveal that in the nπ* state of the thio compounds the molecule exhibits a large out-of-plane "kink" at the sulfur atom. Franck-Condon simulations of the excitation spectra of the V(ππ*) state highlight the activity of various vibrational modes in the neutral chromophore and indicate that upon sulfur substitution internal conversion to the ground state occurs at a significantly higher rate. The similarities observed in the excitation spectra and decay dynamics of the locked and unlocked compounds suggest that in the present experiments single-bond torsion does not show up prominently. The conclusion that for the isolated molecule double-bond torsion is dominating the excited-state dynamics is tentatively confirmed by the quantum-chemical calculations.

Tetrahedron Letters, 1974

Pure and Applied Chemistry, 1994

Progress towards the synthesis of the marine alkaloid manzamine A is described. The synthesis of ... more Progress towards the synthesis of the marine alkaloid manzamine A is described. The synthesis of the ABCD ring system has been achieved, with the macrocyclic D ring being formed by an olefin metathesis cyclization. Additionally, a chiral ABC tricyclic intermediate has been converted into the ring D-nor manzamine A skeleton. The alkaloid manzamine A (l), isolated from the sea sponges Haliclona sp.,latbXestopongia sp.lC and Pellina sp.,2 found in the waters of the Okinawa Sea, exhibits significant antileukemic and antimicrobial activity. The compound possesses an unusual nitrogen-containing pentacyclic fused ring system (ABCDE), bearing a pendant P-carboline moiety. An ingenious hypothetical scheme for the biosynthesis of manzamine A has been proposed by Baldwin and Whitehead.3 According to this scheme, the P-carboline nucleus is completed on the ABCDE template in the last stages of the biosynthesis. The latter aspect has recently received support from the finding that an ABCDE aldehyde, called ircinal A, a constituent of Zrcinia sp., is chemically convertible into manzamine A.4 C02Me

Pure and Applied Chemistry, 1996

The total synthesis of the ABCDE ring system of manzamine A, with the correct absolute stereochem... more The total synthesis of the ABCDE ring system of manzamine A, with the correct absolute stereochemistry at the chiral centers, is described. Key steps in the synthetic route are the formation of both the eight-and the thirteen-membered rings by an olefin metathesis cyclization reaction.

Organic Letters, Jul 18, 2002

A novel method for the synthesis of medium-sized lactams based on an auxiliary-mediated combined ... more A novel method for the synthesis of medium-sized lactams based on an auxiliary-mediated combined tethered/templated strategy is presented. Cyclization by a tethered ring-closing metathesis reaction was followed by a templated transannular aminolysis reaction to give seven-to ten-membered lactams in good yields. Scheme 1. Retrosynthetic Outline of the Combined Tethered/ Templated Approach toward Lactams

Heterocycles, 1988

Obtention de tetrahydro hydroxy-8 ou oxo-8 isoquinoleinetricarboxylates-5,5,7 de triethyle et de ... more Obtention de tetrahydro hydroxy-8 ou oxo-8 isoquinoleinetricarboxylates-5,5,7 de triethyle et de methyl-7 oxo-8 tetrahydro isoquinoleinedicarboxylates-5,7 de diethyle

Chemistry: A European Journal, Nov 7, 2013

ABSTRACT Smooth operation: C-terminal peptide activation with full stereointegrity was accomplish... more ABSTRACT Smooth operation: C-terminal peptide activation with full stereointegrity was accomplished using a copper(II)-mediated coupling reaction of carboxylic acids with arylboroxines (see scheme, NCL = native chemical ligation, Boc = tert-butoxycarbonyl). This method allows epimerization-free activation and ligation of peptides with racemization-prone phenylglycine at the C terminus.

Tetrahedron, 1983

Abstract 2-Substituted 1-tosyl-3,4,4-trimethylimidazolidines prepared by the addition of anions t... more Abstract 2-Substituted 1-tosyl-3,4,4-trimethylimidazolidines prepared by the addition of anions to 1-tosyl-3,4,4-trimethyl-2-imidazolinium iodide 1, react with tryptamine in the presence of acetic acid to give 1-substituted β-carboline derivatives. The salt 1 reacts with anions of 2-[2-(1,3-dithianyl)]benzoates 4a-c to give the corresponding imidazolidines 5a, 5b and 5c, respectively. These transfer the substituted fragment to tryptamine to give pentacyclic products corresponding to the yohimbane skeleton. The product from 5c yields, after reduction of both the amide and the dithiane function, the precursor of epi- and allo-yohimbanes.

Recueil des Travaux Chimiques des Pays-Bas, Sep 2, 2010

Dienamines derived from 8a-methyl-1,6-dioxo-1,2,3,4,6,7,8,8a-octahydronaphthalene (2) and (+)(7aS... more Dienamines derived from 8a-methyl-1,6-dioxo-1,2,3,4,6,7,8,8a-octahydronaphthalene (2) and (+)(7aS)-7a-methyl-2,3,5,6,7,8-hexahydro-1,5(lm-indandione (12) react with 3-bromo-243-methoxypheny1)propene (3) to give the corresponding 5and 4-substituted alkylation products 8 and 14a, respectively. 8 can be directly cyclized to 6-methyl-D-homoequilenin derivative 9 by heating with acid. While 14a can be similarly converted into the corresponding equilenin methyl ether (15a), better yields in the cyclization step are achieved by initial reduction of the 5-ring ketone function and acetylation of the resulting alcohol. The latter sequence of reactions with 14a, derived from 12, gives optically active 17~-acetoxy-6-methylestra-1,3,5,7,9,14-haxaen-3-ol methyl ether (15b), which can serve as an central intermediate for optically active steroids. ' (a) H .

Journal of the Chemical Society, 1979

Suitably substituted imidazolidinium salts serve as N5N10-methenyltetrahydrofolate models in term... more Suitably substituted imidazolidinium salts serve as N5N10-methenyltetrahydrofolate models in terms of their ability to transfer a formyl equivalent to a variety of mono- and bi-functional nucleophiles.

Heterocyclic Communications, 1995

The 8-membered ring Ε has been introduced onto a strategically functionalized chiral pyrrolo[2,3-... more The 8-membered ring Ε has been introduced onto a strategically functionalized chiral pyrrolo[2,3-/]isoquinoline derivative by a combination of a Wittig coupling and amide cyclization. The resulting tetracyclic structure has been converted to the ABCE-ß-carboline ring system of manzamine A. The novel structure and significant biological activity of manzamine A 1-an alkaloid isolated from sea sponges found in the Okinawan waters (1)-has drawn keen attention in connection with its biosynthetic origin (2) and chemical synthesis (3). In a retrosynthetic analysis of the alkaloid, we, and a number of other groups, have recognized that the ABC ring system of manzamine A constitutes a core structure upon which the remaining rings of the target compound may be elaborated. In this context, we reported the first synthesis of the strategically functionalized chiral pyrrolo[2,3-/]isoquinoline intermediate 2 (3d). We now present the elaboration of 2 to the ABCE-ß-carboline ring system of manzamine A.

Tetrahedron, 1983

Abstract Carboxylate esters react with 1,2-diaminoethanes to yield imidazolines, which upon conse... more Abstract Carboxylate esters react with 1,2-diaminoethanes to yield imidazolines, which upon consecutive reaction with acetic anhydride or tosyl chloride and methyl iodide give imidazolinium salts that serve as models of N5,N10-(CH+)-tetrahydrofolate (THF) coenzymes (7a, b and 18a, b). Reduction of the latter salts with sodium borohydride or reaction with anions (R−) give the corresponding 5,10-[CH(H,R)]-THF models. Mono- and bifunctional nucleophiles react with 18a, b to yield carbon-transfer products 6-Alkylamino-1,3-dimethyluracils react with 1 tosyl-3,4,4-trimethylimidazolidine (the reduction product of 18b), in the presence of acetic acid, to form carbon transfer products via a mechanism which bears close analogy to the mechanism of action of thymidylate synthetase.

Recueil des Travaux Chimiques des Pays-Bas, Sep 2, 2010

Under conditions of acid-catalyzed cyclization, migration of the double bond from C-C=CH, to the ... more Under conditions of acid-catalyzed cyclization, migration of the double bond from C-C=CH, to the C=C-CH, system accounts for 20% of the starting acetate.

Angewandte Chemie, Sep 22, 2003

Organic and Biomolecular Chemistry, 2022

Phenol ester activated dipeptides that are reluctant to ring-close have been cyclised with the ai... more Phenol ester activated dipeptides that are reluctant to ring-close have been cyclised with the aid of sterically shielding metallo-porphyrins avoiding unwanted intermolecular reactions. The binding of ZnTPP to the dipyridine-functionalised activating phenolic ester was studied by NMR titrations and modelling. Staudinger-mediated cyclisations in the presence of ZnTPP increased the yield of the cyclic dipeptide from 16% to 40%. † Electronic supplementary information (ESI) available. See

Recueil des Travaux Chimiques des Pays-Bas, 1976

H. Bieraugel et al. j Functionalized enamines-Part X X I V HCL The usual work up afforded 5, b.p.... more H. Bieraugel et al. j Functionalized enamines-Part X X I V HCL The usual work up afforded 5, b.p. 107-110~/0.02 mm, np 1.6710 in 76% yield 'H-NMR spectrum: 6 5.57 (s,-CH=); 6 2.42 and 2.44 (s, I =C-SCH,); 6 2.34(~, =C-SCH,). IR: 2140 cm-' (C=C, m). b. Formation of l.1.4-tris(methylthio)-l-buten-3-yne (5) (second To a suspension of 0.075 mole of sodamide (prepared from sodium and liquid ammonia under the catalytic influence of ferric nitrate) in 250 ml of liquid ammonia were added 8.8 g (0.05 mole) of 23bis(methy1thio)thiophene After stirring for 1 hour the mixture was cooled to-50" and 12 g (0.085 mole) of methyl iodide were added. The ammonia was evaporated by placing the flask in a water bath at 40°. The usual work up gave 5 in 8004 yield. method) c. Formation of 2-methylS -(methylthio)thiophene (6) A solution of 8.8 g (0.05 mole) of 2,5-bis(methylthio)thiophene in 250 ml of THF and 50 ml of HMPT was cooled to-65". To this mixture a solution of 0.09 mole of butyllithium in 45 ml of hexane was added drop by drop at-65O. After the addition the reaction mixture was kept at-400 for 15 minutes and subsequently 14.2 g (0.10 mole) of methyl iodide' were added over 30 minutes with cooling at-60". The mixture was then poured into ice-water. 5-Methyl-2-(methylthio)thiophene (6) (compare 9), b.p. 90-920/ 20 mm, nAo 1.5708, was obtained in 77-80% yield.