Unified strategy for synthesis of indole and 2-oxindole alkaloids

Martin, Stephen F.; Benage, Brigitte; Geraci, Leo S.; Hunter, J. E.; Mortimore, Michael

doi:10.1021/ja00016a036

Cited by 88 publications

(49 citation statements)

References 2 publications

(2 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Accordingly, we designed a second-generation approach to tetrahydroalstonine that required 166 as the key intermediate (Scheme 33). 70 After some experimentation, we discovered a simple, one-step procedure for the synthesis of 166 that featured a vinylogous Mannich reaction of 165 . The subsequent hetero Diels–Alder reaction of 166 then furnished the pentacyclic intermediate 167 .…”

Section: Applications Of Diels–alder Reactions To Alkaloid Synthesismentioning

confidence: 99%

Natural Products and Their Mimics as Targets of Opportunity for Discovery

Martin

2017

J. Org. Chem.

Self Cite

View full text Add to dashboard Cite

Diverse structural types of natural products and their mimics have served as targets of opportunity in our laboratory to inspire the discovery and development of new methods and strategies to assemble polyfunctional and polycyclic molecular architectures. Furthermore, our efforts toward identifying novel compounds having useful biological properties led to the creation of new targets, many of which posed synthetic challenges that required the invention of new methodology. In this Perspective, selected examples of how we have exploited a diverse range of natural products and their mimics to create, explore, and solve a variety of problems in chemistry and biology will be discussed. The journey was not without its twists and turns, but the unexpected often led to new revelations and insights. Indeed, in our recent excursion into applications of synthetic organic chemistry to neuroscience, avoiding the more-traveled paths was richly rewarding.

show abstract

Section: Applications Of Diels–alder Reactions To Alkaloid Synthesismentioning

confidence: 99%

Natural Products and Their Mimics as Targets of Opportunity for Discovery

Martin

2017

J. Org. Chem.

Self Cite

View full text Add to dashboard Cite

show abstract

“…[79] Azacarbazole 73 , available in two steps from tryptamine, was allowed to react with acryloyl chloride 74 to generate N -acyliminium intermediate 75 , which underwent subsequent vinylogous Mannich addition with 1-trimethylsilyloxy-1,3-butadiene. This one-pot sequence rapidly generated intermediate 72 , which contains all the carbon atoms of hydroxyakuammicine ( 41 ).…”

Section: A Selection Of Total Syntheses Of Strychnine and Lessons mentioning

confidence: 99%

Is There No End to the Total Syntheses of Strychnine? Lessons Learned in Strategy and Tactics in Total Synthesis

2012

View full text Add to dashboard Cite

From the 19th century to the present, the complex indole alkaloid strychnine has engaged the chemical community. In this review, we examine why strychnine has been and remains today an important target for directed synthesis efforts. A selection of the diverse syntheses of strychnine is discussed with the aim of identifying their influence on the evolution of the strategy and tactics of organic synthesis.

show abstract

“…Regioselective reduction of the tertiary amide of 159 proceeded cleanly with AlH 3 -Me 2 NEt complex and Et 3 Al, fol-lowed by a NaCNBH 3 work-up to give the tertiary amine in 64-71% yield. 106) N-Methylation of the secondary amide (NaH/MeI in DMF, 94-98%) followed by removal of both protecting groups, (80 eq. trifluoroacetic acid (TFA) in CH 2 Cl 2 ) gave the indole 160 in 59% overall yield from 159.…”

Section: The Total Synthesis Of Paraherquamides a And Bmentioning

confidence: 99%

Total Synthesis and Biosynthesis of the Paraherquamides: An Intriguing Story of the Biological Diels–Alder Construction

Williams

2002

CHEMICAL & PHARMACEUTICAL BULLETIN

View full text Add to dashboard Cite

The paraherquamides constitute an unusual family of prenylated indole alkaloids that are secondary metabolites produced by Penicillium sp. and Aspergillus sp. fungi. This review will cover both the biosynthesis as well as the chemical synthesis of this family of natural products. Particular emphasis will be placed on the provocative hypothesis that the core bicyclo[2.2.2]diazaoctan ring system, which is common to this entire family, is formed by a biological DielsAlder reaction.Despite its widespread use in synthetic organic chemistry, the Diels-Alder cycloaddition reaction does not occur frequently in nature. 1,2) There are just a few reports in the literature claiming the identification of an enzyme that catalyzes this most ubiquitous synthetic ring-forming reaction. [3][4][5][6] A possible explanation for this is that, enzymes generally catalyze reactions by stabilizing the structure and charge of the developing transition state. For most reactions subject to this stratagem of catalysis, both the starting substrate and the product differ significantly with respect to structure from the transition state; it is this fundamental difference that allows for turnover; i.e., both the product and the starting substrate must bind to the enzyme less tightly than the transition state structure. In the Diels-Alder reaction, the transition state is highly ordered and closely resembles the structure of the product (see Fig. 1, below). In other words, an enzyme that was designed to stabilize the transition state structure for this reaction would be expected to be inhibited by the product (via tight binding) and turnover (thus catalysis) would be precluded. It is from within the excitement of this fundamental question, that this review will hold as a guiding light.The only examples of protein-catalyzed Diels-Alder reactions are those of catalytic antibodies that have recently been shown to catalyze the intermolecular [4ϩ2] cycloaddition reaction.7-9) In these cases, the initial Diels-Alder adducts were high-energy substances that significantly change their structure or conformation after the initial cyclocondensation and were subsequently released from the antibody CDR (allowing for turnover). In addition, ribozymes have been reported to catalyze the Diels-Alder reaction and findings in this area have been reviewed. 10) The Penicillium sp. that produces the brevianamides/paraherquamides may be a rare, but vitally important example of the existence of DielsAlderases. It is further significant to note in the context of the catalytic antibody stratagem that, the brevianamide DielsAlder adducts (which are proposed to be the brevianamides themselves) are very rigid substances; therefore, a significant change in conformation or structure is either impossible or highly unlikely. Elucidation of the mechanism for turnover in the purported paraherquamide and brevianamide [4ϩ2] cycloaddition reaction should be an extremely interesting and significant finding.In order to do proper justice to the history of the biosynthetic Diels-Alder p...

show abstract

Unified strategy for synthesis of indole and 2-oxindole alkaloids

Cited by 88 publications

References 2 publications

Natural Products and Their Mimics as Targets of Opportunity for Discovery

Natural Products and Their Mimics as Targets of Opportunity for Discovery

Is There No End to the Total Syntheses of Strychnine? Lessons Learned in Strategy and Tactics in Total Synthesis

Total Synthesis and Biosynthesis of the Paraherquamides: An Intriguing Story of the Biological Diels–Alder Construction

Contact Info

Product

Resources

About

Unified strategy for synthesis of indole and 2-oxindole alkaloids

Cited by 88 publications

References 2 publications

Natural Products and Their Mimics as Targets of Opportunity for Discovery

Natural Products and Their Mimics as Targets of Opportunity for Discovery

Is There No End to the Total Syntheses of Strychnine? Lessons Learned in Strategy and Tactics in Total Synthesis

Total Synthesis and Biosynthesis of the Paraherquamides: An Intriguing Story of the Biological Diels&ndash;Alder Construction

Contact Info

Product

Resources

About

Total Synthesis and Biosynthesis of the Paraherquamides: An Intriguing Story of the Biological Diels–Alder Construction