6870-40-2

Upstream product

• 87960-35-8 3,14-dehydrorauniticine 
• 21372-26-9 trans-5-ethyl-2-oxo-4-piperidineacetic acid ethyl ester 
• 7511-21-9 racemic trans-2-benzoyl-decahydro-6-isoquinolone 
• 20361-93-7 d,l-17β-Hydroxy-16β-17α-dihydroakuammigin 
• 20361-93-7 rac-17ξ-hydroxy-19α-methyl-(20α)-18-oxa-yohimbane-16β-carboxylic acid methyl ester 
• 47485-82-5 serpentine 
• 116005-85-7 21-oxotetrahydroalstonine 
• 116051-32-2 (+/-)-cathenamine 
• 73385-54-3 (7aS,8S,11aS,12aS)-11-Methoxycarbonyl-8-methyl-5,6,7a,8,11a,12,12a,13-octahydro-9-oxa-13-aza-6a-azonia-indeno[2,1-a]anthracene 
• 483-03-4 DL-Akuammigin 
• 24196-11-0 rac-19α-methyl-18-oxa-yohimban-17-one 
• 27130-65-0 rac-19-oxo-corynan-17-oic acid methyl ester; hydrochloride 

Downstream Products

• 5299-09-2 tetrahydroalstonine 
• 483-03-4 tetrahydroalstonine 

Relevant academic research and scientific papers

A Radical Cascade Enabling Collective Syntheses of Natural Products

Natural products have long been important inspirations for the development of chemical methodologies, theories, and technologies, and ultimately, discoveries of new drugs and materials. Chemical syntheses have traditionally yielded individual or small groups of natural products; however, methodology development allowing the synthesis of a large collection of natural products remains scarce. Here, we report an efficient photocatalytic radical cascade method that enables access to libraries of chiral and multiple-ring-fused tetrahydrocarbolinones. The radical cascade can controllably introduce complexity and functionality into products with excellent chemo-, regio-, and diastereoselectivity. The power of this distinct method has been demonstrated by the efficient syntheses of 33 monoterpenoid indole alkaloids belonging to four families.

19-Epialstonine from Amphicome emodi roots

A new indole alkaloid, 19-epialstonine has been isolated from the ethyl acetate extract of the roots of Amphicome emodi. The structure of the alkaloid has been established on the basis of spectroscopic (including 2D NMR experiments) and chemical studies.

Unified strategy for synthesis of indole and 2-oxindole alkaloids

A concise and general entry to representative indole alkaloids of the yohimboid, heteroyohimboid, corynantheoid, and 2-oxindole classes has been developed exploiting a strategy that features intramolecular Diels-Alder reactions for the facile construction of the D/E ring subunits of the target alkaloids. The efficacy of the approach is first illustrated by a two-step total synthesis of the yohimboid alkaloid oxogambirtannine (2) from 22. Thus, the Diels-Alder substrate 25, which was prepared by nucleophilic addition of vinyl ketene acetal 24 to the intermediate N-acyliminium salt formed in situ upon reaction of 22 with 23, was heated in the presence of benzoquinone to give a mixture of diastereoisomeric cycloadducts 26 and 27; these adducts underwent spontaneous oxidation to furnish 2. In another application of the strategy, the [4+2] heterocyclization of 34a, which was formed upon nucleophilic addition of 1-[(trimethylsilyl)oxy]butadiene to the N-acyliminium salt generated in situ upon treatment of 22 with crotonyl chloride, afforded a mixture (ca. 9:1) of cycloadducts 35a and 36a. The major adduct 35a was converted to 42a using a general procedure for effecting β-carbomethoxylation of enol ethers to give vinylogous carbonates. Subsequent reduction of 42a to the heteroyohimboid alkaloids (±)-tetrahydroalstonine (3) and (±)-cathenamine (4) was achieved by selective delivery of 2 or 1 equiv of hydride, respectively. When 42a was treated with sodium amide, stereoselective β-elimination ensued to give 49, which was converted by chemoselective hydride reduction into the corynantheoid alkaloid (±)-geissoschizine (5). Facile access to alkaloids of the 2-oxindole family was realized by using a new protocol for achieving stereoselective, oxidative rearrangements of β-carboline Nb lactams into 3,3-disubstituted 2-oxindoles. Thus, exposure of 42a to tert-butyl hypochlorite followed by acid and silver ion induced rearrangement of the intermediate 3-chloroindolenine gave 50, with only traces of the C(7) epimer being detected. Hydride reduction of 50 gave (±)-isopteropodine (6), acid-catalyzed isomerization of which furnished an equilibrium mixture (1:3) of 6 and (±)-pteropodine (51). The stereochemical course of the intramolecular hetero-Diels-Alder reaction of 34a to give 35a and 36a as the only isolable cycloadducts was examined by computational analysis. The geometry of the six-atom transition state was established by semiempirical methods by using the standard closed-shell, restricted Hartree-Fock (RHF) version of the AM1 method. With use of this constrained geometry for the six-membered pericyclic array, the overall conformational energies for the four possible transition states 52-55 were minimized by MM2 calculations (MacroModel). The calculated relative energies of these transition states were in the order 52 53 54 55. Since the cyclization of 34a produced only 35a and 36a in an approximately 9:1 ratio via the respective transition states 52 and 53, these calculations correlated qualitatively with the experimental results.

A New Indole Alkaloid, 14α-Hydroxyrauniticine: Structure Revision and Partial Synthesis

Oxidation of the enamine (6) with dibenzoyl peroxide followed by reduction with NaBH4 gave the benzoate (8), which was converted to the cis-hydroxyl compound (9), while hydroboration-oxidation of 6 gave the trans-isomer (11).Treatment of a mixture of the enamines (13 and 14) with dibenzoyl peroxide/NaBH4 gave the benzoates (15 and 16), which were converted to 14α-hydroxy-3-isorauniticine (17) and the acetal (18), respectively.Hydroboration-oxidation of 13 gave 14α-hydroxyrauniticine (2), which was found to be identical with the natural alkaloid whose structure had erroneously been proposed as 14β-hydroxy-3-isorauniticine (4).Keywords-indole alkaloid; 14α-hydroxyrauniticine; structure revision; partial synthesis; Uncaria attenuata; enamine; hydroxylation; hydroboration

INTRODUCTION OF HYDROXYL GROUP AT C-14 OF INDOLE ALKALOIDS: THE PARTIAL SYNTHESIS OF 14α-HYDROXYRAUNITICINE

Stereoselective hydroxylation at C-1 of the indoloquinolizidine (1) to the hydroxyl derivatives (5 and 6) and the partial synthesis of 14α-hydroxyrauniticine (11) from rauniticine (7) are described.

INTERCONVERSION OF THE ENAMINE AND IMMONIUM FORM OF CATHENAMINE

From the amount of deuterium incorporated during the reduction of cathenamine to tetrahydroalstonine, the enamine and immonium ion form of cathenamine was demonstrated.The two forms could be interconverted depending on the presence or absence of SO4(-2).

GENERAL METHODS OF SYNTHESIS OF INDOLE ALKALOIDS - 14. SHORT ROUTES OF CONSTRUCTION OF YOHIMBOID AND AJMALICINOID ALKALOID SYSTEMS AND THEIR 13C NUCLEAR MAGNETIC RESONANCE SPECTRAL ANALYSIS.

Conceptually new schemes of synthesis of indole alkaloids are introduced. The yohimboid ring system is constructed by the sequential treatment of 1-tryptophyl-3-( beta -ketobutyl)pyridinium bromide with base and acid. Hydrogenation of the product yields d,l-pseudoyohimbone. The ajmalicinoid ring system is formed by the exposure of 1-tryptophyl-3-acetylpyridinium bromide to sodio dimethyl malonate and then to acid, followed by hydrogenation. Subsequent reduction and dehydration of the products lead to the racemates of the alkaloids tetrahydroalstonine and akuammigine as well as isomers of ajmalicine. Shifts of specific carbons are found to be of stereochemically diagnostic value.