Asymmetric total synthesis of the indole alkaloid cyclopiazonic acid and first structure-activity data

The indole alkaloid α-cyclopiazonic acid (CPA) is one of the few known inhibitors of sarco(endo)plasmic reticulum Ca²⁺-ATPase (SERCA) besides the terpenoids thapsigargin and artemisinin. We report here the first asymmetric total synthesis of cyclopiazonic acid by a modification of the Knight synthesis, currently the most efficient route to CPA. First structure-activity data of CPA derivatives and stereoisomers are presented and will be discussed in connection with the published crystal structures of CPA-SERCA complexes.     

Total synthesis and stereochemical reassignment of the indole alkaloid vinoxine

The first total synthesis of the indole alkaloid vinoxine and the reassignment of the relative configuration at carbon-16 in this alkaloid is reported.     

First total synthesis of trimeric indole alkaloid, psychotrimine

The first total synthesis of (+/-)-psychotrimine, a novel trimeric indole alkaloid isolated from Psychotria rostrata, was achieved. In the total synthesis, the copper-mediated intramolecular and intermolecular aminations of halobenzenes, which respectively contributed to the construction of a pyrrolidinoindoline core and the installation of a third tryptamine unit, were used as key steps.     

Enantioselective total synthesis of briarellins E and F: the first total syntheses of briarellin diterpenes

Enantioselective total syntheses of briarellin E (4) and briarellin F (5) have been achieved starting with (S)-(+)-carvone and (S)-(-)-glycidol. These total syntheses are the first of briarellin diterpenes. The central step in these syntheses is acid-promoted condensation of cyclohexadienyl diol 15 and (Z)-alpha,beta-unsaturated aldehyde 16 to form, with complete stereocontrol, the hexahydroisobenzofuran core and six stereocenters of these coral metabolites. These syntheses also feature stereospecific photolytic deformylation of beta,gamma-unsaturated aldehyde 17 to remove the extraneous carbon introduced in the Prins-pinacol step, chemo- and stereoselective hydroxyl-directed epoxidation of dienyl alcohol 18 to incorporate the C3 oxygen stereocenter, regio- and stereoselective rearrangement of epoxy ester 19 to install the C4 oxygen substituent, efficient dehydrative cyclization of a 1,6-diol intermediate to form the oxepane ring, and diastereoselective Nozaki-Hiyama-Kishi cyclization of vinyl iodide aldehyde 25 to forge the oxacyclononane ring and the C6 hydroxyl stereocenter. These total syntheses establish the absolute configurations of 4 and 5, define a concise strategy for the total synthesis of briarellin diterpenes, and provide additional illustrations of the uncommon utility of pinacol-terminated cationic cyclizations for stereocontrolled synthesis of complex oxacyclic natural products.     

Fischer indole synthesis of the indoloquinoline alkaloid: cryptosanguinolentine

A new synthesis of an indoloquinoline alkaloid, isolated from Cryptolepis sanguinolenta, is described using a Fischer indole cyclization. 4-Hydroxy-1-methyl-1H-quinolin-2-one reacted directly with phenylhydrazine hydrochloride to give the indoloquinoline, which was reacted with POCl₃ and then the resultant halide hydrogenolysed to give cryptosanguinolentine.     

Total synthesis of (±)-neoechinulin A,an indole alkaloid containing oxidized diketopiperazine

Protected neoechinulin A ($\text{Z}$ isomer) and its $\text{E}$ isomer were synthesized by condensation of N-bis(methylthiomethyl)cyclo(Ala-Gly) with 2-(1,1-dimethyl-2-propenyl)-1-methoxymethylindole-3-aldehyde; deprotection of both isomers gave neoechinulin A, whose $\text{Z}$ configuration was rigorously established. A novel cyclization of the protected neoechinulin A into a seven-membered cyclic compound was reported.     

Enantioselective synthesis of marine indole alkaloid hamacanthin B

An enantioselective total synthesis of hamacanthin B (1) is described. This synthesis is based on the asymmetric synthesis of (S)-2-azido-(indol-3-yl)ethylamine 7, which is coupled with the 3-indolyl-alpha-oxoacetyl chloride 8 and subsequently used in a successful intramolecular Staudinger-aza Wittig cyclization to form the central dihydropyrazinone ring. The stereochemistry of naturally isolated hamacanthin B is revealed as the (S)-configuration.     

Formation of an unusual dimeric compound by lead tetraacetate oxidation of a corynanthe-type indole alkaloid,mitragynine

Lead tetraacetate oxidation of a Corynanthe-type indole alkaloid, mitragynine, produced mainly 7-acetoxyindolenine derivative (2) together with a dimeric compound (4) as a minor product. The novel structure having a bridge between the C-11' and C-7 positions in the respective indolenine parts and its formation mechanism were studied.     

Total synthesis of the marine alkaloid halitulin

The structure of the strongly cytotoxic marine alkaloid halitulin (1) has been confirmed by total synthesis and its absolute configuration determined as (15S). The synthesis follows a strategy previously reported by one of us and uses an efficient preparation of the quinoline-7,8-diol unit by modified Baeyer-Villiger and Skraup reactions. The O-benzyl protecting groups were removed in the last step of the synthesis by transfer hydrogenolysis without concomitant reduction of the quinoline ring. The method can be applied for the synthesis of halitulin analogues.     

Total synthesis of the naphthyridine alkaloid jasminine

The synthesis of (±)-jasminine (1), a member of a small group of naphthyridine alkaloids, has been achieved. The synthetic route takes advantage of the reactivity of dihydropyridine intermediates for the preparation of trisubstituted pyridine 4, which gives access to the alkaloid by a reductive amination-lactamization tandem reaction.     

Total synthesis of the racemic alkaloid diptocarpamine

A route for the synthesis of racemic diptocarpamine from hex-5-enoic acid has been developed.Institute of Chemistry, Bashkir Scientific Center of the Urals Branch, USSR Academy of Sciences, Ufa. Institute of the Chemistry of Plant Substances, Uzbek SSR Academy of Sciences, Tashkent. Translated from Khimiya Prirodnykh Soedinenii, No. 2, pp. 232–236, March–April, 1989.     

Total synthesis of the Amaryllidaceae alkaloid clivonine

Two syntheses of the Amaryllidaceae alkaloid clivonine (1) are described. Both employ previously reported 7-arylhydrindane 6 as an intermediate but differ in the method employed for subsequent introduction of what becomes the ring-B lactone carbonyl carbon (C7). The synthesis featuring a Bischler-Napieralski reaction for this transformation constitutes the first asymmetric synthesis of natural (+)-clivonine. Crystal structures for compounds (±)-13, (±)-16, (-)-20 and (±)-28 are also reported.     

General approach for the synthesis of sarpagine/ajmaline indole alkaloids. Stereospecific total synthesis of the sarpagine alkaloid (+)-vellosimine

[reaction: see text] (+)-Vellosimine has been synthesized enantiospecifically in 27% overall yield from commercially available D-(+)-tryptophan methyl ester via the asymmetric Pictet-Spengler reaction and a stereocontrolled intramolecular palladium-coupling reaction as key steps.     

synthesis of sempervirine,a pentacyclic anhydronium indole alkaloid

Summary Sempervirine (2,3,4,13-tetrahydro-1H-benz[g]indolo[2,3-a]quinolizin-6-ium,1) the pentacyclic anhydronium indole alkaloid ofGelsemium sempervirens Ait. f. (Loganiaceae), has been synthesized in three steps from hexahydroisochroman-3-one (6) and N-2-(3-indolyl)-ethylamine (tryptamine,7). The condensation product, N-2-(3-indolyl)-ethyl-2-(hydroxymethyl)-trans-hexahydrophenylacetamide (8) arising from6 and7 on double cyclization with phosphoryl chloride yielded the 3,4-dehydroyohimbane derivative9. Aromatization of rings C and D of compound9 with 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ) in glacial acetic acid, followed by basification, generated sempervirine (1).

---

Synthese von Sempervirin, einem pentacyclischen Anhydronium-Indolalkaloid

Zusammenfassung Sempervirin (2,3,4,13-Tetrahydro-1H-benz[g]indolo[2,3-a]chinolizin-6-ium,1), das pentacyclische Anhydronium-Indolalkaloid vonGelsemium sempervirens Ait f. (Loganiceae) wurde ausgehend von Hexahydroisochroman-3-on (6) und N-2-(3-Indolyl)-ethylamin (Tryptamin,7) in 3 Stufen synthetisiert. Das durch doppelte Cyclisierung von6 und7 mit Phosphorylchlorid entstehende Kondensationsprodukt N-2-(3-Indolyl)-ethyl-2-(hydroxymethyl)-trans-hexahydrophenylacetamid (8) ergab das 3,4-Dehydroyohimbanderivat9. Aromatisierung der Ringe C und D von9 mit 2,3-Dichlor-5,6-dicyanobenzochinon (DDQ) in Eisessig und anschließende Einstellung eines basischenpH-Werts lieferte Sempervirin (1).

     

A total synthesis of the alkaloid deplancheine

The indole alkaloid deplancheine (1) has been synthesised utilising a Witting reaction on the octahydro[2,3-a]quinolizin-2-one (2) itself available in four synthetic steps from readily available materials.     

Total synthesis of amaryllidaceae alkaloid buflavine

A concise synthesis of the amaryllidaceae alkaloid buflavine (1) and its regioisomer (2) involving sequential Meyers' biaryl coupling, enecarbamate formation, and hydrogenation followed by ultimate intramolecular reductive amination is presented.     

Total syntheses of five indole alkaloids from the marine bryozoan Flustra foliacea

A general, efficient, and conceptually new approach to the total syntheses of marine-derived indole alkaloids, including (+/-)-flustramines A (1) and B (2), (+/-)-flustramides A (3) and B (4), and (+/-)-debromoflustramine B (5), is outlined. The key step in the syntheses involves the conjugated addition of an organomagnesium species derived from prenyl bromide to 2-hydroxyindolenines. Compounds 1, 2, and 5 have been synthesized in five steps with 23%, 17%, and 16% overall yield, respectively, whereas flustramides 3 and 4 have been synthesized in only four steps with 24% and 18% overall yield, respectively, on the basis of 2-hydroxyindolenines.