First total synthesis of the 7,3'-linked naphthylisoquinoline alkaloid ancistrocladidine

[structure: see text] The first total synthesis of the rare 7,3'-linked naphthylisoquinoline alkaloid, ancistrocladidine, has been completed. The key feature of the synthesis is the formation of the extremely hindered biaryl linkage by Pinhey-Barton ortho-arylation of a naphthol with an aryllead triacetate. The biaryl aldehyde formed is elaborated in 10 steps to form a 1:1 mixture of ancistrocladidine and its atropisomer. Recrystallization of the mixture afforded ancistrocladidine, which was identical in all respects to the reported data.     

A first and general route to naphthylisoquinoline alkaloids: the total synthesis of O-methyl-tetradehydro-triphyophylline

The first total synthesis of a naphthylisoquinoline alkaloid is described. The required $\text{ortho}$ selective mixed coupling of the alkaloid moieties 2 and 6 is achieved $\text{intra}$-molecularly by the assistance of a reversibly thrown benzylether type auxiliary bridge.     

Total synthesis of the 7,3'-linked naphthylisoquinoline alkaloid ancistrocladidine

The first total synthesis of ancistrocladidine, a rare 7,3'-linked naphthylisoquinoline alkaloid, has been completed, with the key feature of the synthesis being the formation of the extremely hindered biaryl linkage by ortho-arylation of a naphthol with an aryllead triacetate. Initial efforts were focused on the generation of a heteroaryl lead species, which would have allowed a convergent synthesis to be developed. However, it was not possible to generate such a lead species. A simpler aryl lead triacetate was prepared and reacted. The resulting biaryl aldehyde was elaborated in 10 steps to form a 1:1 mixture of ancistrocladidine and its atropisomer. Recrystallization of the mixture afforded ancistrocladidine, which was identical in all respects to the reported data.     

Isocomplestatin: total synthesis and stereochemical revision

A Pd-mediated method for preparation of the strained macrocyclic moiety of complestatins is disclosed. Through stereoselective synthesis of model macrocycles and the S atropisomer of complestatin, the stereochemical identity of the anti-HIV agent complestatin is established. Investigations described herein illustrate that the compound previously reported as isocomplestatin is the same as complestatin. Thus, the S atropisomer of complestatin is the true isocomplestatin and has not been isolated as a natural product.     

Azedaralide: total synthesis, relative and absolute stereochemical assignment

Azedaralide, a potentially advanced intermediate for the total synthesis of various tetranortriterpenes, was constructed utilising the Fernández-Mateos protocol and assigned both relative and absolute stereochemistries. Both asymmetric aldol and classical chiral resolution attempts failed to deliver pure enantiomers whereas preparative chiral chromatography resolved racemic azedaralide with ease.     

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.     

The first enantiospecific total synthesis of a C-quaternary voachalotine alkaloid, (+)-dehydrovoachalotine

The first enantiospecific total synthesis of the indole alkaloid (+)-dehydrovoachalotine (1) has been achieved from d-(+)-tryptophan methyl ester in 28% overall yield. The formation of the prochiral quaternary carbon center at C-16 in the key intermediate (12) was realized via a Tollens reaction from N_a-methylvellosimine (13) in 95% yield. This approach could also be applied to the synthesis of many other indole alkaloids that contain a quaternary carbon center at C(16).     

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.     

Ancisheynine, a novel naphthylisoquinolinium alkaloid from Ancistrocladus heyneanus

A novel naphthylisoquinoline alkaloid, ancisheynine 1, was isolated from the aerial part of Ancistrocladus heyneanus Wallich ex J. Graham (Ancistrocladaceae). Ancisheynine 1 contained a previously undescribed N-2,C-8′-linkage between the isoquinoline and naphthalene units and its structure was established by spectroscopic methods.     

Murrastifoline-F: first total synthesis, atropo-enantiomer resolution, and stereoanalysis of an axially chiral N,C-coupled biaryl alkaloid.

The first total synthesis of the Murraya alkaloid murrastifoline-F (3), an unsymmetric, N,C-bonded heterobiarylic biscarbazole, is described. Starting from the likewise naturally occurring-but here synthetically prepared-"monomer" murrayafoline-A (6), lead tetraacetate-mediated oxidative non-phenolic biaryl coupling gives 3 as the main regioisomer. The existence of this natural product as a pair of stable atropo-enantiomers was demonstrated analytically through LC-CD investigations. Preparatively, the racemate resolution succeeded by O-demethylation, derivatization with Mosher's reagent, and chromatographic separation of the resulting diastereomers. The absolute configurations of the atropisomers were assigned by CD spectroscopy in combination with quantum chemical CD calculations at the stage of the alkaloid 3 and by ROESY experiments of the diastereomeric Mosher derivatives. In the root extract of the curry leaf plant Murraya koenigii (Rutaceae), murrastifoline-F (3) was found to exist as a 56:44 mixture in favor of the M-enantiomer, by LC-CD coupling.     

Rubrenolide, total synthesis and revision of its reported stereochemical structure

In this paper the synthesis of the natural product rubrenolide is presented. Due to an error in the original proposed stereochemical structure of rubrenolide, the synthesis was not straightforward. Application of the photo-induced rearrangement of an appropriate epoxy diazomethyl ketone gave access to the precursor lactone with an ee of 91%. Coupling of this lactone with (4S)-2,2-dimethyl-[1,3]-dioxolane-4-carbaldehyde gave, after some additional steps, the final product that was identical with an authentic sample of the natural product.     

One-pot total synthesis: the first total synthesis of chiral alkaloid pimprinol A and the facile construction of its natural congeners from amino acids

In this work, we accomplished the first total synthesis of chiral alkaloid pimprinol A and the facile construction of its natural congeners: pimprinine, pimprinethine, pimprinaphine, WS-30581A, WS-30581B, laboradorin 1, uguenenazole, balsoxine, texamine in one-pot from commercially available starting materials including amino acids. Further investigating into the mechanism revealed that this improved transformation was achieved by the integration of iodination, Kornblum oxidation, condensation, decarboxylation, annulation, and oxidation reaction sequence.     

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.     

Enantiospecific,stereospecific total synthesis of the oxindole alkaloid alstonisine

[reaction: see text] The total synthesis of alstonisine was accomplished in enantiospecific fashion in an overall yield of 12% (from tryptophan methyl ester) in 17 reaction vessels. The structure of alstonisine (1) has been determined by NOE spectroscopic experiments and was confirmed by single-crystal X-ray analysis.     

Determination of absolute configuration of Pandanus alkaloid, pandamarilactonine-A, by first asymmetric total synthesis

The absolute configuration of pandamarilactonine-A, a pyrrolidine alkaloid, was established on the basis of total synthesis starting from l-prolinol. An insight into the mechanism of the low enantiomeric purity of natural pandamarilactonine-A is discussed.     

The first regiospecific, enantiospecific total synthesis of 6-oxoalstophylline and an improved total synthesis of alstonerine and alstophylline as well as the bisindole alkaloid macralstonine

A Wacker sequence has been modified to rapidly generate ring E of (-)-alstonerine, (+)-6-oxoalstophylline, and (-)-alstophylline via a domino process. This one-pot sequence provides facile entry into the dihydropyranyl enone unit of many Alstonia alkaloids. [structure: see text]     

First total synthesis and stereochemical revision of okaramine M

We describe the first total synthesis of the reported and revised structures of okaramine M (1 and 7) through the Ugi three-component reaction of pyrroloindole imine 10 with p-methoxyphenyl isonitrile and N-Boc-l-tryptophan, followed by cyclization and epimerization.     

The total synthesis and stereochemical revision of yanucamide A

[reaction: see text] The first total synthesis of yanucamide A is reported via amide and ester couplings of the key components. This synthesis has established the configuration at the previously ambiguous 3-position, and also revised the stereochemistry at the 22-position, to give 3S,12S,17S,22S for the natural product.     

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.