Limits...
Studies on C20-diterpenoid alkaloids: synthesis of the hetidine framework and its application to the synthesis of dihydronavirine and the atisine skeleton.

Hamlin AM, Lapointe D, Owens K, Sarpong R - J. Org. Chem. (2014)

Bottom Line: The application of the hetidine framework to the synthesis of dihydronavirine, which is the formal reduction product of the natural product navirine, is also described.Key to the success of these studies is the use of a Ga(III)-catalyzed cycloisomerization reaction of alkynylindenes to prepare a [6-7-6] framework that was advanced to the hetidine skeleton.Furthermore, a Michael/aldol sequence was developed for the construction of the bicyclo[2.2.2] framework that is characteristic of the hetidines and atisines.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, University of California , Berkeley, California 94720, United States.

ABSTRACT
The full details of a synthesis of the hetidine framework of the C20-diterpenoid alkaloids and its conversion to the atisine core structure are reported. The application of the hetidine framework to the synthesis of dihydronavirine, which is the formal reduction product of the natural product navirine, is also described. Key to the success of these studies is the use of a Ga(III)-catalyzed cycloisomerization reaction of alkynylindenes to prepare a [6-7-6] framework that was advanced to the hetidine skeleton. Furthermore, a Michael/aldol sequence was developed for the construction of the bicyclo[2.2.2] framework that is characteristic of the hetidines and atisines.

Show MeSH
Representative C20-diterpenoid alkaloids andderivativesin the atisine, hetidine, and hetisine subclass.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4120980&req=5

fig2: Representative C20-diterpenoid alkaloids andderivativesin the atisine, hetidine, and hetisine subclass.

Mentions: The diterpenoid alkaloids(see representative examples in Figure 1) area collection of complex alkaloids isolatedfrom the Ranunculaceae and Rosaceae family of plants.1 These molecules are among the most architecturally complexnatural products isolated to date. In addition to their imposing skeletalintricacy, they possess varied, yet dense, arrays of hydroxylation.To date, over 1100 natural products have been isolated and classifiedas diterpenoid alkaloids. On the basis of the number of constituentcarbons, these natural products are described as C18-,C19-, or C20-diterpenoid alkaloids. The majorityof these metabolites have been isolated from the Aconitum, Consolida, Delphinium, Rumex, and Spiraea genera, and extractsfrom these plants have been used in traditional Eastern herbal medicinefor centuries as sedatives and fever reducers. Other pharmacologicaleffects that have been discovered in these plants, including analgesiceffects and anti-inflammatory, myorelaxant, and antiarrhythmic properties,are also attributed to their diterpenoid alkaloid constituents. Overall,this broad spectrum of biological activity likely arises because ofthe potent interactions of these alkaloids with voltage-dependentsodium, potassium, and calcium ion channels. The pharmaceutical potentialof the diterpenoid alkaloids is continuing to emerge, and already,lappaconitine (allapinin, 1) and guan-fu base A (13, Figure 2; also known as acehytisinehydrochloride)2 are marketed as antiarrhythmiaagents.34


Studies on C20-diterpenoid alkaloids: synthesis of the hetidine framework and its application to the synthesis of dihydronavirine and the atisine skeleton.

Hamlin AM, Lapointe D, Owens K, Sarpong R - J. Org. Chem. (2014)

Representative C20-diterpenoid alkaloids andderivativesin the atisine, hetidine, and hetisine subclass.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4120980&req=5

fig2: Representative C20-diterpenoid alkaloids andderivativesin the atisine, hetidine, and hetisine subclass.
Mentions: The diterpenoid alkaloids(see representative examples in Figure 1) area collection of complex alkaloids isolatedfrom the Ranunculaceae and Rosaceae family of plants.1 These molecules are among the most architecturally complexnatural products isolated to date. In addition to their imposing skeletalintricacy, they possess varied, yet dense, arrays of hydroxylation.To date, over 1100 natural products have been isolated and classifiedas diterpenoid alkaloids. On the basis of the number of constituentcarbons, these natural products are described as C18-,C19-, or C20-diterpenoid alkaloids. The majorityof these metabolites have been isolated from the Aconitum, Consolida, Delphinium, Rumex, and Spiraea genera, and extractsfrom these plants have been used in traditional Eastern herbal medicinefor centuries as sedatives and fever reducers. Other pharmacologicaleffects that have been discovered in these plants, including analgesiceffects and anti-inflammatory, myorelaxant, and antiarrhythmic properties,are also attributed to their diterpenoid alkaloid constituents. Overall,this broad spectrum of biological activity likely arises because ofthe potent interactions of these alkaloids with voltage-dependentsodium, potassium, and calcium ion channels. The pharmaceutical potentialof the diterpenoid alkaloids is continuing to emerge, and already,lappaconitine (allapinin, 1) and guan-fu base A (13, Figure 2; also known as acehytisinehydrochloride)2 are marketed as antiarrhythmiaagents.34

Bottom Line: The application of the hetidine framework to the synthesis of dihydronavirine, which is the formal reduction product of the natural product navirine, is also described.Key to the success of these studies is the use of a Ga(III)-catalyzed cycloisomerization reaction of alkynylindenes to prepare a [6-7-6] framework that was advanced to the hetidine skeleton.Furthermore, a Michael/aldol sequence was developed for the construction of the bicyclo[2.2.2] framework that is characteristic of the hetidines and atisines.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, University of California , Berkeley, California 94720, United States.

ABSTRACT
The full details of a synthesis of the hetidine framework of the C20-diterpenoid alkaloids and its conversion to the atisine core structure are reported. The application of the hetidine framework to the synthesis of dihydronavirine, which is the formal reduction product of the natural product navirine, is also described. Key to the success of these studies is the use of a Ga(III)-catalyzed cycloisomerization reaction of alkynylindenes to prepare a [6-7-6] framework that was advanced to the hetidine skeleton. Furthermore, a Michael/aldol sequence was developed for the construction of the bicyclo[2.2.2] framework that is characteristic of the hetidines and atisines.

Show MeSH