András Toró

TRANSANNULAR DIELS-ALDER MODEL STUDIES ON THE TOTAL SYNTHESIS OF CHATANCIN. THE FURANOPHANE APPROACH. PART 1 : ASSEMBLY OF THE ACYCLIC SUBSTRATES

Abstract Synthesis of three generations of model substrates with advancing similarity to chatancin are presented. In the first two generations, an Ireland-Claisen based six-step sequence supplied the trans -dienophile to be connected by dithiane chemistry to furfurals. In the third generation, a homogeraniol based dienophile aldehyde was coupled with a dilithiated 3-furoic acid. Subsequently, all three generations were concluded with similar functional group modifications as a preparation for a malonate-furyl chloride based macrocyclization.

Transannular Diels-Alder model studies on the total synthesis of chatancin. The furanophane approach. Part 2 [1]: Macrocyclization and Diels-Alder reaction

Abstract Title investigation of three generations of model substrates targeting chatancin is presented. An unfunctionalized furan affords a reversible transannular Diels-Alder reaction producing only the two TAC -frameworks where the expected one is the kinetic product. A furan 3-COOMe functionalization allows the selective formation of the expected isomer which is still favored even in the presence of a quasi-axial isopropyl group on the furanophane.

Oxidative decarboxylation of 17(20)-dehydro-2,324-dinorcholanoic acids

Abstract 17(20)-dehydro-23,24-dinorcholan-22-oic acids, derived from natural sterols are converted with H 2 O 2 in the presence of molybdate or tungstate ions into 16-unsaturated 20-oxo-pregnanes, which are useful intermediates of corticosteroid hormones and drugs.

Transannular Diels-Alder studies on the asymmetric synthesis of (+)-maritimol

Abstract Assembly of 13-membered TCC macrocyclic trienes are described and their transannular Diels-Alder reaction are investigated as a model study for the asymmetric synthesis of the ABC-ring system of (+)-maritimol. Albeit the original expectations that the pro-3(S)- and 4(R)-functionalities induce perfect absolute and relative control in the strategic step has not been fully met, a position at pro-12(R) complying with these requirements is recognized.

Synthesis of 17α-hydroxy-20-oxo-pregnanes from 17(20)-dehydro-23,24-dinorcholan-22-oic acids

Abstract Title transformation involving catalytic epoxidation, Curtius rearrangement and acidic hydrolysis has been accomplished. This synthetic sequence offers a novel route from a partial microbial side chain degradation product of natural sterols into useful precursors of antinflammatory, antiandrogen and gestagen pharmaceuticals.

Synthesis of chiral trans-syn-cis and trans-anti-trans [6.6.6] tricycles by transannular Diels-Alder reaction

Abstract Stereocontrolled asymmetric synthesis and transannular Diels-Alder (TADA) reaction of a 14-membered trans-cis-cis (TCC) macrocyclic trienone with an activated dienophile leading to an A.B.C [6.6.6] tricycle having one angular methyl group is reported. The results of thermal and Lewis acid catalyzed TADA reaction are discussed.

Macrocyclization of terminal bis-allylic chlorides via an intramolecular gem-dialkylation of malononitrile or methyl cyanoacetate

Abstract A procedure is described for the stereospecific synthesis of 13-membered trienic macrocycles from suitable acyclic bis-allylic chlorides via an intramolecular gem-dialkylation of malononitrile or methyl cyanoacetate.

Synthesis of 16-dehydro-20-oxopregnanes from 17α,20-epoxy-23,24-dinorcholan-22-oic acids. Highly stereospecific oxirane → allyl alcohol isomerization of an epoxycarboxylic acid

Abstract A microbial degradation product of natural sterols was converted into traditional precursor of steroid syntheses by a simple sequence. The title isomerization, the key step, was investigated to demonstrate a concerted mechanism, in which a cyclic transition state, involving the oxirane oxygen, the β- and γ-carbon, the γ-proton to be removed and the catalyst coordinated by the carboxylate group, is postulated.

Transannular Diels–Alder Studies of 14-Membered cis–trans–trans Macrocyclic Trienes Having Allylic Ether or Enone Dienophile

Highly convergent, malonate alkylation based syntheses of the model macrocycles and their title investigations are reported. In the allylic ether dienophile case, a preference for tricycles with equatorial ether position was found at the transition state level. Ab initio calculations also show that the origin of this preference is not only steric but stereoelectronic as well. The enone dienophile case indicates that when the enone system is not totally twisted out of planarity by the macrocyclic environment, the Diels–Alder reaction follows the usual trend in terms of dienophile activation.

Facile Synthesis of Methyl 2-Formyl-5-hydroxymethyl-3-furancarboxylate

Abstract A short practical synthesis of the title trisubstituted furan is presented. It involves a high yield Knoevenagel condensation of glyceraldehyde and methyl acetoacetate to the furan nucleus and, following a protection of the furyl alcohol, a radical bromination then a Krohnke reaction of the furyl bromide intermediate.