Classical carbonyl reactivity enables a short synthesis of the core structure of acutumine

The development of a direct synthesis of the complex core topology of the alkaloid acutumine from a simple keto proline derivative is described. An efficient sequence of three carbonyl-dependent reactions is at the heart of this design for synthesis.     

Unprecedented cyclisations of calix[4]arenes with glycols under the Mitsunobu protocol. Part 1: A new perspective for the synthesis of calixcrowns

Selective ring closures of p-tert-butylthiacalix[4]arene and p-tert-butylcalix[4]arene with oligoethylene glycols were performed under the Mitsunobu protocol using the DEAD/TPP system. The method opens a new perspective for the syntheses of 1,3-calixcrowns.     

Oxidative rearrangement of indoles: a new approach to the EFHG-tetracyclic core of diazonamide A

A new approach to the ring EFHG-tetracyclic core fragment of the marine secondary metabolite diazonamide A is described. The route is based on the oxidative rearrangement of 3-arylindole-2-carboxylates. Thus, a range of 3-arylindole-2-carboxylates (3, 8) underwent rearrangement to the corresponding 3,3-disubstituted oxindoles (4, 9) with migration of the ester group upon treatment with tert-butyl hypochlorite followed by acid. The oxindoles 9 with a 3-[2-(4-methoxybenzyloxy)]phenyl substituent underwent cyclization to the tetracyclic aminals 11 following N-protection, reduction, and treatment with methanesulfonic anhydride. The methodology was applied to the tyrosine-indole derivative 17 to give the EFHG-tetracyclic core of diazonamide A.     

Steroselective synthesis of the basic skeleton of aphidicolan diterpenes: synthetic approach to aphidicolin

The basic skeleton of aphidicolan-type diterpenes was stereoselectively synthesized via thermolysis of a benzocyclobutene.     

A concise synthesis of the tricyclic skeleton of pleuromutilin and a new approach to cycloheptenes

[reaction: see text] A short synthesis of the tricyclic skeleton of pleuromutilin is reported, featuring an unusually efficient 8-endo-trig radical cyclization of a xanthate precursor. In the course of this study, a one-carbon ring expansion leading to cycloheptenes was uncovered.     

A connective approach to the tetrahydropyran subunit of polycavernoside A via a novel 1,1-dianion equivalent

Racemic tetrahydropyran 3 was efficiently synthesised from allylsilane 6 and aldehyde 7 via an intramolecular Sakurai cyclisation. In a single step, the relative configuration of three chiral centres was established. Allylsilane 6 was readily assembled from 1-iodo-1-selenopropene 10, a synthetic equivalent of a propene 1,1-dianion.     

Synthesis of vinca alkaloids and related compounds. Part 110: A new synthetic method for the preparation of pandoline-type alkaloid-like molecules

A practicable synthesis of a pandoline-type alkaloid-like molecule is reported through an efficient preparation of carbinolamine ether intermediates (9a and 9b). The key step of the synthesis consists of an intramolecular cycloaddition of the secodine-type intermediate (2), which was formed from the tryptamine derivative (3) and lactol (4). The mechanism of the cycloaddition reaction was investigated by quantum chemical calculations and it was found to follow a step-wise mechanism involving a zwitterionic intermediate (15). By employing this strategy, other members of the family of pandoline alkaloids or alkaloid-like molecules could be synthesized by reacting the tryptamine derivative with appropriately functionalized aldehydes.     

A convergent approach to the marine natural product eleutherobin: synthesis of key intermediates and attempts to produce the basic skeleton

Synthesis of (1R,5R,6R)-2-(6-hydroxymethyl-5-isopropyl-2-methylcyclohex-2-enyl)-N- methoxy-N-methylacetamide 8 from R-(-)-phellandrene in six steps, and (3aR*,4S*,6R*,6aS*)- (6-hydroxymethyl-4-methoxy-2,2,6-trimethyltetrahydrofuro[3,4-d][1,3]dioxol- 4-yl)acetic acid methyl ester 17 from tetrabromoacetone and 2-methoxy-5-methylfuran in six steps, provided two key fragments which have been combined to produce intermediates for attempted construction of the basic skeleton of eleutherobin.     

A new approach to the synthesis of lamotrigine and other 3,5-diamino-1,2,4-triazine derivatives

A new in principle method for the synthesis of 6-aryl(hetaryl)-3,5-diamino-1,2,4-triazines by decomposition of pre-synthesized tetrazolo[1,5-b][1,2,4]triazines was developed. The advantages of this method over traditional methods were demonstrated using the synthesis of a modern antiepileptic preparation lamotrigine, as an example.__________Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 713–719, March, 2005.     

Reactivity of spiroanthraceneoxazolidines with cyclopropanes: An approach to the oxindole alkaloid scaffold

The reaction of N-methylspiro[anthracene-oxazolidine] with spiro[cyclopropane-3,3′-indolin]-2-ones in the presence of MgI₂ formed the corresponding spiro[pyrrolidine-3,3′-indolin]-2-ones in 42–65% yields. The use of N-benzylspiro[anthracene-oxazolidine] in this reaction led to the formation of a mixture of the corresponding N-methyl- and N-benzylpyrrolidines.     

A new approach to organomanganese compounds: the tellurium/manganese exchange reaction

Diorganomanganese compounds react with aryl, vinyl, and alkynyl tellurides in a tellurium/manganese exchange reaction. The new mixed organomanganese reagents react selectively with electrophiles.     

A biomimetic type expedient approach to the tricyclic core of xyloketals. Application to a short, stereocontrolled synthesis of alboatrin and a remarkable epi to natural isomerisation

An expedient synthesis of the linear tetrahydrofurano benzopyran ring system of xyloketals is described involving an ortho ester Claisen rearrangement and an intramolecular cationic cyclisation. This strategy was applied for a short, stereocontrolled and high yield synthesis of the phytotoxic metabolite alboatrin.     

A highly selective Ir-catalyzed borylation of 2-substituted indoles: a new access to 2,7- and 2,4,7-substituted indoles

The selective CH-functionalization of 2-substituted indoles is presented. Using bis(pinacolato)diboron (2) in the presence of iridium complexes, a novel catalytic mono-borylation is observed preferentially at the 7-position of the indole. This allows for an efficient synthesis of various 2,7-di- and 2,4,7-trisubstituted indoles, which are otherwise difficult to access. The scope and limitation of the method is demonstrated.     

A direct entry to the 1-methoxyindole skeleton and to the corresponding indoles by a novel rearrangement: general syntheses of substituted 1-methoxyindoles

A short and efficient route to 1-methoxyindoles via a novel rearrangement is disclosed. This route involves only three steps from commercially available nitro compounds. The methodology is also generalized with a variety of examples to afford a series of 2-substituted-1-methoxyindoles possessing an electron-withdrawing group at position 3. In addition, a 1-methoxyindole compound 10 was converted to the corresponding indole 11 under mild conditions thereby constituting a new synthesis of substituted indoles.     

Synthesis of vinca alkaloids and related compounds. Part 108: Efficient convergent synthetic pathway to the ibophyllidine skeleton IV. First synthesis of (±)-18-hydroxy-20-epiibophyllidine

The first total synthesis of the pentacyclic alkaloid (±)-18-hydroxy-20-epiibophyllidine was realized via an efficient preparation of the d-seco-pseudoaspidospermane molecule. The key step of the sequence involves an intramolecular [4+2] cycloaddition reaction of the dihydrosecodine intermediate, which was built up from the reaction of a tryptamine derivative with an aldehyde-ester. After full epimerization, the intramolecular N-alkylation of the tetracyclic ester gave the pentacyclic compound. Reduction of the latter molecule led to the title compound.     

Combining two-directional synthesis and tandem reactions. Part 4: A concise approach to the spirocyclic core of halichlorine and the pinnaic acids

A synthesis of the spirocyclic core structure of halichlorine, an inhibitor of the induced expression of VCAM-1 and the pinnaic acids, inhibitors of PLA₂, is presented. A two-directional strategy is employed, in conjunction with a tandem oxime formation/Michael addition/cycloaddition to form the key azaspirocyclic skeleton in a very direct manner.     

Rifamycin antibiotics—new compounds and synthetic methods. Part 1: Study of the reaction of 3-formylrifamycin SV with primary alkylamines or ammonia

Within the study covering the search for new methods of synthesis of rifamycin antibiotics, the reactions of 3-formylrifamycin SV (2) with primary amines or ammonia were studied. In the reaction of 2 with methylamine, unstable 3-methyliminomethylrifamycin SV (8) was formed, which was further oxidised to stable 3-methyliminomethylrifamycin S (9). In the reaction of 2 with ammonia, N,15-didehydro-15-deoxo-pyrimido-(4,5-b)rifamycin SV (10), a new compound with a chromophore system enlarged by a pyrimidine ring, was obtained. The product of its reduction with sodium borohydride—(11)—was also isolated. The structures of the compounds and an explanation of the synthesis mechanism have been proposed on the basis of mass spectrometry results as well as (1D) and (2D) ¹H- and ¹³C NMR analysis. In vitro antituberculous activity of the new compounds have been investigated.