Total Synthesis of Lycopodium Alkaloids PDF Download

Author: Edward Fox Kleinman
Publisher:
ISBN:
Category :
Languages : en
Pages : 350

View

Book Description

Author: Sarah Elizabeth House
Publisher:
ISBN:
Category :
Languages : en
Pages : 370

View

Book Description
A unified approach to the total synthesis of Lycopodium alkaloids belonging to the miscellaneous class has been developed, wherein a single tetracyclic amine is employed as a common intermediate in synthetic studies toward several alkaloids. An overview of Lycopodium alkaloids is presented, including their structural classification, isolation and biological activity. The biosynthesis of alkaloids in the miscellaneous group is discussed in depth. A summary of previous synthetic work focusing on miscellaneous Lycopodium alkaloids is presented, including total syntheses of luciduline, lyconadins A and B and nankakurines A and B.A model study of spirolucidine is discussed. A biomimetic route to access spirolucidine and nankakurine B has been investigated. In this study, a tetracyclic amine that is a key intermedite in the total synthesis of lyconadin A previously developed in our laboratory is elaborated into a tertiary alcohol that mimics the proposed biosynthetic precursor of nankakurine B.A biomimetic ring-contractive [alpha]-hydroxyimine rearrangement to generate nankakurine B has been extensively investigated and found to be disfavored. The conversion of a tricyclic ketone (first synthesized en route to lyconadin A) to the tetracyclic core of serratezomine D has been investigated. The core of this molecule was inaccessible via methods employed in the studies toward lyconadin A. The total synthesis of 1'-epi-dihydrolycolucine from the key common tetracyclic amine intermediate has been achieved. Studies toward the synthesis of serratezomine E served as a platform to develop this method and to determine the stereochemical outcome of this reaction.

Author: Todd Andrew Blumenkopf
Publisher:
ISBN:
Category :
Languages : en
Pages : 648

View

Book Description

Author: Michael David Purdham
Publisher:
ISBN:
Category :
Languages : en
Pages : 198

View

Book Description

Author: Mrinmoy Saha
Publisher:
ISBN:
Category : Alkaloids
Languages : en
Pages : 451

View

Book Description
Lycopodium alkaloids have shown widespread and noteworthy biological activity, consisting of over 250 known natural products. Moreover, their structural complexity and diversity have attracted considerable attention from numerous laboratories including our own. Recently, we have developed a unified approach that would provides access to numerous, previously unprepared C10-functionalized lycopodium alkaloids. The first enantioselective total syntheses of all C10-hydroxy lycopodium alkaloids have been accomplished. We have also made a significant progress towards himeradine A and other C10-functionlyzed pentacyclic lycopodium alkaloids. Key steps in the synthetic sequence towards C10-hydroxy lycopodium alkaloids include construction of six-membered ring using an organocatalyzed intramolecular Michael reaction, formation of tricyclic skeleton using a conformationally accelerated Mannich reaction and a tandem Oppenauer oxidation / aldol condensation cascade reaction to form the tetracyclic skeleton of the natural products. A proline sulfonamide catalyst has been explored and expanded for the intramolecular Michael reaction for the construction of common six-membered ring for all the C10-functionalized lycopodium alkaloids. During our endeavor towards the sis- membered ring formation it was observed that rate of the Michael reaction and conversion to product increases dramatically in presence of the proline sulfonamide catalyst. The effect of C10 stereochemistry (both R and S) was also explored in the Michael reaction and (R)-C10-epimer proved to give better diastereoselectivity during the process. A conformationally accelerated, intramolecular Mannich reaction route was utilized to the tricyclic skeleton of all C10-hydroxy lycopodium alkaloids to construct C4- C13. During the Mannich reaction the effect of C10 stereochemistry was explored as well and it was found that C4-C13 bond could only be formed with (R)-C10-epimer. In addition, protecting group on C10 alcohol has significant effect on the intramolecular Mannich reaction. We have accomplished the first enantioselective total synthesis of 10-hydroxylycopodine, deacetylpaniculine and paniculine. During our endeavor towards these natural products we have utilized an Oppenauer oxidation/aldol condensation cascade reaction to form the tetracyclic skeleton from the tricyclic intermediate. We have reported the first fully characterized NMR data for 10-hydroxylycopodine and optical rotation data for all the C10-hydroxy lycopodium alkaloids. Key aspects towards the C10-functionalyzed lycopodium alkaloids are Mander's reagent -mediated one carbon homologation, a tandem sulfone rearrangement / intramolecular Mannich cyclization to form the key tricyclic skeleton and synthesis of the advanced C10-alcohol intermediate towards the western portion of himeradine A. Additionally, the western portion of himeradine A will serve as the common intermediate towards related pentacyclic C10-functionalyzed lycopodium alkaloids. During the synthesis of the tricyclic C10-alcohol, several routes have been explored to functionalize the C4 center and finally the Mander's reagent strategy successfully installed the C3 ester. A significant tricyclic skeleton towards the pentacyclic C10-functionalyzed lycopodium alkaloids was achieved through utilization of a tandem 1,3-sulfone rearrangement/intramolecular Mannich reaction as the key steps. Polymer supported PPh3 was utilized to improve the yield of the Aza-Wittig / Mannich reaction sequence. We have discovered that the incorporation of the methyl-protecting group on C5-enol and reduction of the C3 ester to alcohol was necessary in order to successfully facilitate the C14-desulfurization.

Author: Hans-Joachim Knoelker
Publisher: Springer Science & Business Media
ISBN: 3642255280
Category : Science
Languages : en
Pages : 268

View

Book Description
Lycopodium Alkaloids: Isolation and Asymmetric Synthesis, by Mariko Kitajima and Hiromitsu Takayama.- Synthesis of Morphine Alkaloids and Derivatives, by Uwe Rinner and Tomas Hudlicky.- Indole Prenylation in Alkaloid Synthesis, by Thomas Lindel, Nils Marsch and Santosh Kumar Adla.- Marine Pyrroloiminoquinone Alkaloids, by Yasuyuki Kita and Hiromichi Fujioka.- Synthetic Studies on Amaryllidaceae and Other Terrestrially Derived Alkaloids, by Martin G. Banwell, Nadia Yuqian Gao, Brett D. Schwartz and Lorenzo V. White.- Synthesis of Pyrrole and Carbazole Alkaloids, by Ingmar Bauer and Hans-Joachim Knölker.-

Author: Felix Hartrampf
Publisher:
ISBN:
Category :
Languages : en
Pages :

View

Book Description

Author: Damian Winston Young
Publisher:
ISBN:
Category :
Languages : en
Pages : 193

View

Book Description
Keywords: heterocycles, spirolucidine, alkaloids, dihydropyridones.

Author: Gregory Wayne Schwing
Publisher:
ISBN:
Category :
Languages : en
Pages : 140

View

Book Description

Author: William Russell Bowman
Publisher:
ISBN:
Category : Alkaloids
Languages : en
Pages : 0

View

Book Description
The structure of the Lycopodium alkaloid lycofawcine (base L)(74) isolated by R. H. Burnell has been determined by the use of mass spectral analysis. The proposed structure was confirmed by transformation of lycofawcine into O-acetylacrifoline. The total synthesis of lycodine (6) was attempted but was not brought to a successful conclusion. The total synthesis of dl-lycopodine (1) has been achieved via a natural relay compound. A method for transforming 11-substituted cis - cis -hexahydrojulolidines (A) into the corresponding cis - trans -hexahydrojulolidines (B) has been developed.