Author: Praveen Kokkonda
Publisher:
ISBN:
Category :
Languages : en
Pages : 232
Book Description
The Strychnos class of indole alkaloids contain a pyrrolo[2,3-d]carbazole ABCE tetracyclic framework. The second-generation ABCE tetracycle approach was employed in the total synthesis of (±)-20-epi-lochneridine and progress toward total synthesis of (±)-alstolucine B. The second-generation approach featured Mitsunobu activation of the hydroxyethyl group in a gramine intermediate followed by intramolecular aza-Baylis-Hillman reaction. The substrate for hydroboration was redesigned to (±)-18-desmethyl akuammicine (1,1-disubstituted double bond), since the hydroboration of trisubstituted alkenes afforded tertiary alcohol via Markovnikov addition. The key steps were n-Bu3SnH mediated cyclization reaction to accomplish D-ring, tert-butyl hypochlorite indoline oxidation, and anti-Markovnikov hydroboration to introduce a primary alcohol. The total syntheses of Strychnos-Strychnos type bis-indole alkaloids (−)-leucoridine A and C were accomplished from the biomimetic dimerization of (−)-dihydrovalparicine. En route to (−)-dihydrovialparicine, known alkaloids (+)-geissoschizoline and (−)-dehydrogeissoschizoline were also prepared from commercially available N-tosyl indole 3-carboxaldehyde. Key steps consisted of an in situ dimerization of (−)-dihydrovalparicine from (−)-1, 2-dehydrogeissoschizoline with trifluoroacetic acid in the presence of 4 Å molecular sieves. Acid mediated ring-opening of the indolenine in (−)-leucoridine A to afford (−)-leucoridine C. DFT calculations were employed to elucidate the mechanism of dimerization, which suggested that a stepwise aza-Michael/spirocyclization sequence was preferred over the alternate hetero Diels-Alder cycloaddition reaction. A novel domino Michael/Mannich [4+2] annulation method was applied for concise total synthesis of Aspidospermatan alkaloids (+)-20-epi-condyfoline and progress toward the total synthesis of (+)-condyfoline. The additional key steps consisted of a LiHMDS mediated cyclization to form D-ring, dimethyl(methylthio)sulfonium tetrafluoroborate (DMTSF) mediated spirocyclization to form pentacyclic thioether and indoline oxidation with MnO2.
TOTAL SYNTHESIS OF STRYCHNOS AND ASPIDOSPERMATAN ALKALOIDS
Author: Praveen Kokkonda
Publisher:
ISBN:
Category :
Languages : en
Pages : 232
Book Description
The Strychnos class of indole alkaloids contain a pyrrolo[2,3-d]carbazole ABCE tetracyclic framework. The second-generation ABCE tetracycle approach was employed in the total synthesis of (±)-20-epi-lochneridine and progress toward total synthesis of (±)-alstolucine B. The second-generation approach featured Mitsunobu activation of the hydroxyethyl group in a gramine intermediate followed by intramolecular aza-Baylis-Hillman reaction. The substrate for hydroboration was redesigned to (±)-18-desmethyl akuammicine (1,1-disubstituted double bond), since the hydroboration of trisubstituted alkenes afforded tertiary alcohol via Markovnikov addition. The key steps were n-Bu3SnH mediated cyclization reaction to accomplish D-ring, tert-butyl hypochlorite indoline oxidation, and anti-Markovnikov hydroboration to introduce a primary alcohol. The total syntheses of Strychnos-Strychnos type bis-indole alkaloids (−)-leucoridine A and C were accomplished from the biomimetic dimerization of (−)-dihydrovalparicine. En route to (−)-dihydrovialparicine, known alkaloids (+)-geissoschizoline and (−)-dehydrogeissoschizoline were also prepared from commercially available N-tosyl indole 3-carboxaldehyde. Key steps consisted of an in situ dimerization of (−)-dihydrovalparicine from (−)-1, 2-dehydrogeissoschizoline with trifluoroacetic acid in the presence of 4 Å molecular sieves. Acid mediated ring-opening of the indolenine in (−)-leucoridine A to afford (−)-leucoridine C. DFT calculations were employed to elucidate the mechanism of dimerization, which suggested that a stepwise aza-Michael/spirocyclization sequence was preferred over the alternate hetero Diels-Alder cycloaddition reaction. A novel domino Michael/Mannich [4+2] annulation method was applied for concise total synthesis of Aspidospermatan alkaloids (+)-20-epi-condyfoline and progress toward the total synthesis of (+)-condyfoline. The additional key steps consisted of a LiHMDS mediated cyclization to form D-ring, dimethyl(methylthio)sulfonium tetrafluoroborate (DMTSF) mediated spirocyclization to form pentacyclic thioether and indoline oxidation with MnO2.
Publisher:
ISBN:
Category :
Languages : en
Pages : 232
Book Description
The Strychnos class of indole alkaloids contain a pyrrolo[2,3-d]carbazole ABCE tetracyclic framework. The second-generation ABCE tetracycle approach was employed in the total synthesis of (±)-20-epi-lochneridine and progress toward total synthesis of (±)-alstolucine B. The second-generation approach featured Mitsunobu activation of the hydroxyethyl group in a gramine intermediate followed by intramolecular aza-Baylis-Hillman reaction. The substrate for hydroboration was redesigned to (±)-18-desmethyl akuammicine (1,1-disubstituted double bond), since the hydroboration of trisubstituted alkenes afforded tertiary alcohol via Markovnikov addition. The key steps were n-Bu3SnH mediated cyclization reaction to accomplish D-ring, tert-butyl hypochlorite indoline oxidation, and anti-Markovnikov hydroboration to introduce a primary alcohol. The total syntheses of Strychnos-Strychnos type bis-indole alkaloids (−)-leucoridine A and C were accomplished from the biomimetic dimerization of (−)-dihydrovalparicine. En route to (−)-dihydrovialparicine, known alkaloids (+)-geissoschizoline and (−)-dehydrogeissoschizoline were also prepared from commercially available N-tosyl indole 3-carboxaldehyde. Key steps consisted of an in situ dimerization of (−)-dihydrovalparicine from (−)-1, 2-dehydrogeissoschizoline with trifluoroacetic acid in the presence of 4 Å molecular sieves. Acid mediated ring-opening of the indolenine in (−)-leucoridine A to afford (−)-leucoridine C. DFT calculations were employed to elucidate the mechanism of dimerization, which suggested that a stepwise aza-Michael/spirocyclization sequence was preferred over the alternate hetero Diels-Alder cycloaddition reaction. A novel domino Michael/Mannich [4+2] annulation method was applied for concise total synthesis of Aspidospermatan alkaloids (+)-20-epi-condyfoline and progress toward the total synthesis of (+)-condyfoline. The additional key steps consisted of a LiHMDS mediated cyclization to form D-ring, dimethyl(methylthio)sulfonium tetrafluoroborate (DMTSF) mediated spirocyclization to form pentacyclic thioether and indoline oxidation with MnO2.
Strategies and Tactics in Organic Synthesis
Author: Gopal Sirasani
Publisher: Elsevier Inc. Chapters
ISBN: 0128056045
Category : Science
Languages : en
Pages : 39
Book Description
Described herein is an account of my laboratory’s entry into the magnificent field of complex alkaloid total synthesis, spanning the development of novel methods for quickly assembling polycyclic frameworks through the total synthesis of various members of the Strychnos alkaloids. A discussion of the prior art related to our approach to these alkaloids in addition to strategic decisions and reasoning made en route to targets akuammicine ( 1 ), strychnine ( 2 ), and leuconicines A ( 3 ) and B ( 4 ) is carefully detailed. Finally, we present the retrosynthetic analyses of the aforementioned targets and respective total syntheses thereof (including asymmetric variants).
Publisher: Elsevier Inc. Chapters
ISBN: 0128056045
Category : Science
Languages : en
Pages : 39
Book Description
Described herein is an account of my laboratory’s entry into the magnificent field of complex alkaloid total synthesis, spanning the development of novel methods for quickly assembling polycyclic frameworks through the total synthesis of various members of the Strychnos alkaloids. A discussion of the prior art related to our approach to these alkaloids in addition to strategic decisions and reasoning made en route to targets akuammicine ( 1 ), strychnine ( 2 ), and leuconicines A ( 3 ) and B ( 4 ) is carefully detailed. Finally, we present the retrosynthetic analyses of the aforementioned targets and respective total syntheses thereof (including asymmetric variants).
Studies Toward the Total Synthesis of Strychnos Alkaloids
Author: Steven Roger Angle
Publisher:
ISBN:
Category :
Languages : en
Pages : 428
Book Description
Publisher:
ISBN:
Category :
Languages : en
Pages : 428
Book Description
Studies Directed Toward the Total Synthesis of the Strychnos Alkaloids
Author: Robert Wells Marquis
Publisher:
ISBN:
Category :
Languages : en
Pages : 260
Book Description
Publisher:
ISBN:
Category :
Languages : en
Pages : 260
Book Description
Synthetic Studies Towards the Total Synthesis of Strychnos Alkaloids
Author: Johannes Nicolaas Zonjee
Publisher:
ISBN:
Category :
Languages : en
Pages : 136
Book Description
Publisher:
ISBN:
Category :
Languages : en
Pages : 136
Book Description
NOVEL APPROACHES TO STRYCHNOS AND ASPIDOSPERMA ALKALOIDS
Author: Senzhi Zhao
Publisher:
ISBN:
Category :
Languages : en
Pages : 363
Book Description
All Strychnos and Aspidosperma alkaloids possess a core pyrrolo[2,3-d]carbazole ABCE tetracycle. In order to develop an efficient and divergent methodology for the synthesis of Strychnos alkaloids, a streamlined synthetic sequence to the ABCE tetracycle has been developed. It features a Mitsunobu activation of an N-hydroxyethyl gramine intermediate and subsequent intramolecular aza-Baylis-Hillman reaction. This method was first applied in the total synthesis of (±)-alstolucine B. Additional key steps in the synthesis included (1) chemoselective intermolecular and intramolecular Michael additions and (2) a Swern indoline oxidation. The second application of this method was in the first total synthesis of (-)-melotenine A, a novel rearranged Aspidosperma alkaloid with potent biological activity. Additional key steps in the synthesis included (1) a Piers annulation of a vinyl iodide and a methyl ketone to prepare the D ring and (2) a site-selective intermolecular vinylogous aldol reaction.
Publisher:
ISBN:
Category :
Languages : en
Pages : 363
Book Description
All Strychnos and Aspidosperma alkaloids possess a core pyrrolo[2,3-d]carbazole ABCE tetracycle. In order to develop an efficient and divergent methodology for the synthesis of Strychnos alkaloids, a streamlined synthetic sequence to the ABCE tetracycle has been developed. It features a Mitsunobu activation of an N-hydroxyethyl gramine intermediate and subsequent intramolecular aza-Baylis-Hillman reaction. This method was first applied in the total synthesis of (±)-alstolucine B. Additional key steps in the synthesis included (1) chemoselective intermolecular and intramolecular Michael additions and (2) a Swern indoline oxidation. The second application of this method was in the first total synthesis of (-)-melotenine A, a novel rearranged Aspidosperma alkaloid with potent biological activity. Additional key steps in the synthesis included (1) a Piers annulation of a vinyl iodide and a methyl ketone to prepare the D ring and (2) a site-selective intermolecular vinylogous aldol reaction.
Synthesis of Strychnos Alkaloids
Author: Christopher Scott Brook
Publisher:
ISBN:
Category : Alkaloids
Languages : en
Pages : 734
Book Description
Publisher:
ISBN:
Category : Alkaloids
Languages : en
Pages : 734
Book Description
Studies Toward the Synthesis of Strychnos Alkaloids
Author: Albert Peter Paul
Publisher:
ISBN:
Category : Alkaloids
Languages : en
Pages : 236
Book Description
Publisher:
ISBN:
Category : Alkaloids
Languages : en
Pages : 236
Book Description
Synthesis, Transformations, and Chemical Correlations of Strychnos and Mitragyna Alkaloids
Author: William Banks Hinshaw
Publisher:
ISBN:
Category : Alkaloids
Languages : en
Pages : 308
Book Description
Publisher:
ISBN:
Category : Alkaloids
Languages : en
Pages : 308
Book Description
Towards the Synthesis of Monoterpenoids Indole Alkaloids of the Aspidospermatan and Strychnan Type
Author: Dawood Hosni Dawood
Publisher:
ISBN:
Category :
Languages : en
Pages : 0
Book Description
The aim of this work was to access the skeleton of the Aspidosperma and the Strychnos alkaloids using arylcyclohexa-2,5-dienes as common synthetic precursors. Initially, these arylcyclohexadienes were synthesized through Birch reductive alkylation reactions. The desymmetrization of these cyclohexadienes was developed via the Michael addition reaction, providing the Büchi ketone, the tetracyclic core of Aspidosperma alkaloids, in only 6 steps and 17% overall yield. On the other hand, we described the oxidative amination reaction catalyzed by metals (Pd, Cu). The palladium oxidative amination reaction allowed a fast access to the pentacyclic framework of aza-aspidospermanes and the tetracyclic framework of the strychnos. In parallel, we have described an approach toward the pentacyclic skeleton of mossambine and strychnine.
Publisher:
ISBN:
Category :
Languages : en
Pages : 0
Book Description
The aim of this work was to access the skeleton of the Aspidosperma and the Strychnos alkaloids using arylcyclohexa-2,5-dienes as common synthetic precursors. Initially, these arylcyclohexadienes were synthesized through Birch reductive alkylation reactions. The desymmetrization of these cyclohexadienes was developed via the Michael addition reaction, providing the Büchi ketone, the tetracyclic core of Aspidosperma alkaloids, in only 6 steps and 17% overall yield. On the other hand, we described the oxidative amination reaction catalyzed by metals (Pd, Cu). The palladium oxidative amination reaction allowed a fast access to the pentacyclic framework of aza-aspidospermanes and the tetracyclic framework of the strychnos. In parallel, we have described an approach toward the pentacyclic skeleton of mossambine and strychnine.