Browse
Submit Data
Databases
API
Help

Dataset Information

18 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Total Syntheses of the C₁₉ Diterpenoid Alkaloids (-)-Talatisamine, (-)-Liljestrandisine, and (-)-Liljestrandinine by a Fragment Coupling Approach.

ABSTRACT: The C19 diterpenoid alkaloids (C19 DTAs) are a large family of natural products, many of which modulate the activity of ion channels in vivo and are therefore of interest for the study of neurological and cardiovascular diseases. The complex architectures of these molecules continue to challenge the state-of-the art in chemical synthesis, particularly with respect to efficient assembly of their polcyclic ring systems. Here, we report the total syntheses of (-)-talatisamine, (-)-liljestrandisine, and (-)-liljestrandinine, three aconitine-type C19 DTAs, using a fragment coupling strategy. Key to this approach is a 1,2-addition/semipinacol rearrangement sequence which efficiently joins two complex fragments and sets an all-carbon quaternary center.

SUBMITTER: Wong AR

PROVIDER: S-EPMC8393236 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

A Unifying Synthesis Approach to the C18-, C19-, and C20-Diterpenoid Alkaloids.

Project description:The secondary metabolites that comprise the diterpenoid alkaloids are categorized into C18, C19, and C20 families depending on the number of contiguous carbon atoms that constitute their central framework. Herein, we detail our efforts to prepare these molecules by chemical synthesis, including a photochemical approach, and ultimately a bioinspired strategy that has resulted in the development of a unifying synthesis of one C18 (weisaconitine D), one C19 (liljestrandinine), and three C20 (cochlearenine, paniculamine, and N-ethyl-1α-hydroxy-17-veratroyldictyzine) natural products from a common intermediate.

| S-EPMC6372304 | biostudies-literature

Total syntheses of arylindolizidine alkaloids (+)-ipalbidine and (+)-antofine.

Project description:This paper presents the first application of two recently developed reactions to natural product synthesis. The first method involves a 6-endo-trig cyclization to prepare a versatile chiral enaminone building block. The second is a direct C-H arylation reaction. As a showcase for the utility of these methods, (+)-antofine and (+)-ipalbidine were synthesized in only 8 steps and 24-26% overall yields.

| S-EPMC2948484 | biostudies-literature

Syntheses of Denudatine Diterpenoid Alkaloids: Cochlearenine, N-Ethyl-1?-hydroxy-17-veratroyldictyzine, and Paniculamine.

Project description:The denudatine-type diterpenoid alkaloids cochlearenine, N-ethyl-1?-hydroxy-17-veratroyldictyzine, and paniculamine have been synthesized for the first time (25, 26, and 26 steps from 16, respectively). These syntheses take advantage of a common intermediate (8) that we have previously employed in preparing aconitine-type natural products. The syntheses reported herein complete the realization of a unified strategy for the preparation of C20, C19, and C18 diterpenoid alkaloids.

| S-EPMC5076861 | biostudies-literature

A convergent approach to batzelladine alkaloids. Total syntheses of (+)-batzelladine E, (-)-dehydrobatzelladine C, and (+)-batzelladine K.

Project description:We recently reported a convergent strategy to access the polycyclic guanidinium alkaloid (+)-batzelladine B via an aldol addition-retro-aldol-aza-Michael addition cascade. Here we describe the application of this approach toward the total syntheses of (+)-batzelladine E, (-)-dehydrobatzelladine C, and (+)-batzelladine K. The identification of suitable methods to functionalize a common tropane core by electrophilic alkynylation and nucleophilic 1,2-addition were essential to generalizing this approach. We provide evidence for the intermediacy of an acylallene species in the cascade reaction.

| S-EPMC8078486 | biostudies-literature

Enantioselective Total Syntheses of Methanoquinolizidine-Containing Akuammiline Alkaloids and Related Studies.

Project description:The akuammiline alkaloids are a structurally diverse class of bioactive natural products isolated from plants found in various parts of the world. A particularly challenging subset of akuammiline alkaloids are those that contain a methanoquinolizidine core. We describe a synthetic approach to these compounds that has enabled the first total syntheses of (+)-strictamine, (-)-2( S)-cathafoline, (+)-akuammiline, and (-)-?-akuammigine. Our strategy relies on the development of the reductive interrupted Fischer indolization reaction to construct a common pentacyclic intermediate bearing five contiguous stereocenters, in addition to late-stage formation of the methanoquinolizidine framework using a deprotection-cyclization cascade. The total syntheses of (-)-?-akuammigine and (+)-akuammiline mark the first preparations of akuammiline alkaloids containing both a methanoquinolizidine core and vicinal quaternary centers. Lastly, we describe the bioinspired reductive rearrangements of (+)-strictamine and (+)-akuammiline to ultimately provide (-)-10-demethoxyvincorine and a new analogue thereof.

| S-EPMC6085837 | biostudies-literature

A tandem Prins/Schmidt reaction approach to marine alkaloids: formal and total syntheses of lepadiformines A and C.

Project description:The tricyclic core of the cylindricine or lepadiformine families of alkaloid natural products was assembled via a Prins addition/intramolecular Schmidt rearrangement under Lewis acid conditions. Both single-pot and two-stage variations of this process were examined, with particular attention to the stereochemical outcome of the processes. This technology has been applied to a formal total synthesis of lepadiformine A and a total synthesis of lepadiformine C.

| S-EPMC2846845 | biostudies-literature

Unified Approach to Prenylated Indole Alkaloids: Total Syntheses of (-)-17-Hydroxy-Citrinalin B, (+)-Stephacidin A, and (+)-Notoamide I.

Project description:A unified strategy for the synthesis of congeners of the prenylated indole alkaloids is presented. This strategy has yielded the first synthesis of the natural product (-)-17-hydroxy-citrinalin B as well as syntheses of (+)-stephacidin A and (+)-notoamide I. An enolate addition to an in situ generated isocyanate was utilized in forging a key bicyclo[2.2.2]diazaoctane moiety, and in this way connected the two structural classes of the prenylated indole alkaloids through synthesis.

| S-EPMC4583210 | biostudies-literature

Calyciphylline B-Type Alkaloids: Total Syntheses of (-)-Daphlongamine H and (-)-Isodaphlongamine H.

Project description:The first total synthesis of the complex hexacylic Daphniphyllum alkaloid (-)-daphlongamine H has been accomplished. Key to the success of the strategy are a complexity-building Mannich reaction, efficient cyclizations, and a highly diastereoselective hydrogenation to assemble multigram quantities of the tricyclic core bearing four contiguous stereocenters. Following construction of the hydro-indene substructure by means of a Pauson-Khand reaction, endgame redox manipulations delivered the natural product. Importantly, the synthetic studies have also given access to (-)-isodaphlongamine H and led to a revision of the reported structure of deoxyisocalyciphylline B.

| S-EPMC6750003 | biostudies-literature

A Benzyne Insertion Approach to Hetisine-Type Diterpenoid Alkaloids: Synthesis of Cossonidine (Davisine).

Project description:The hetisine-type natural products exhibit one of the most complex carbon skeletons within the diterpenoid alkaloid family. The use of network analysis has enabled a synthesis strategy to access alkaloids in this class with hydroxylation on the A-ring. Key transformations include a benzyne acyl-alkylation to construct a key fused 6-7-6 tricycle, a chemoselective nitrile reduction, and sequential C-N bond formations using a reductive cyclization and a photochemical hydroamination to construct an embedded azabicycle. Our strategy should enable access to myriad natural and unnatural products within the hetisine-type.

| S-EPMC6342194 | biostudies-literature

A Unified Approach to Polycyclic Alkaloids of the Ingenamine Estate: Total Syntheses of Keramaphidin B, Ingenamine, and Nominal Njaoamine I.

Project description:Many polycyclic marine alkaloids are thought to derive from partly reduced macrocyclic alkylpyridine derivatives via a transannular Diels-Alder reaction that forms their common etheno-bridged diaza-decaline core ("Baldwin-Whitehead hypothesis"). Rather than trying to emulate this biosynthesis pathway, a route to these natural products following purely chemical logic was pursued. Specifically, a Michael/Michael addition cascade provided rapid access to this conspicuous tricyclic scaffold and allowed different handles to be introduced at the bridgehead quarternary center. This flexibility opened opportunities for the formation of the enveloping medium-sized and macrocyclic rings. Ring closing alkyne metathesis (RCAM) proved most reliable and became a recurrent theme en route to keramaphidin B, ingenamine, xestocyclamine A, and nominal njaoamine I (the structure of which had to be corrected in the aftermath of the synthesis). Best results were obtained with molybdenum alkylidyne catalysts endowed with (tripodal) silanolate ligands, which proved fully operative in the presence of tertiary amines, quinoline, and other Lewis basic sites. RCAM was successfully interlinked with macrolactamization, an intricate hydroboration/protonation/alkyl-Suzuki coupling sequence, or ring closing olefin metathesis (RCM) for the closure of the second lateral ring; the use of RCM for the formation of an 11-membered cycle is particularly noteworthy. Equally rare are RCM reactions that leave a pre-existing triple bond untouched, as the standard ruthenium catalysts are usually indiscriminative vis-à-vis the different π-bonds. Of arguably highest significance, however, is the use of two consecutive or even concurrent RCAM reactions en route to nominal njaoamine I as the arguably most complex of the chosen targets.

| S-EPMC8431342 | biostudies-literature