Synthesis of 2-isopropylfuro(2,3-b)quinolines-a new synthesis of (±)-lunacrine, (±)-lunasine and (±)-demethoxylunacrine

A new and convenient synthesis of 2-isopropylfuro-(2,3-b)quinolines ($\text{4}$) from 3-(3-methylbut-1-enyl)-2-quinolones ($\text{2}$) is described. A neat synthesis of the alkaloids (±)-lunacrine ($\text{1a}$), (±)-lunasine ($\text{12a}$) and (±)-demethoxylunacrine ($\text{1b}$) is also reported.     

Formal total synthesis of β-pipitzol

(±)-$\text{O}$-methylperezone ($\text{1b}$) was obtained by selective oxidative demethylation of (±)-leucoperezone trimethyl ether ($\text{4a}$). Compound ($\text{4a}$) was prepared by condensation of 2,3,5-trimethoxytoluene ($\text{5e}$) with 6-methyl-5-hepten-2-one, followed by reductive removal of the tertiary alcohol. The aromatic precursor $\text{5e}$ was prepared in four steps from 2,3-dimethoxytoluene ($\text{5a}$) and, alternatively, in three steps from 5-bromoveratraldehyde ($\text{6a}$). Racemic $\text{1b}$ and $\text{4a}$ were directly compared with the optically active molecules prepared from natural R(-)-perezone ($\text{1a}$).     

The synthesis of γ-fluoroisoleucine

Condensation of 3-fluoro-2-butanone ($\text{2}$) with alkyl diethylphosphonoacetates ($\text{4a–d}$) gave alkyl 4-fluoro-3-methyl-2-pentenoates ($\text{5a–d}$). Addition of bromine yielded alkyl-2,3-dibromo-4-fluoro-3-methylpentanoates ($\text{6a,b}$) which were dehydrobrominated to alkyl 2-bromo-4-fluoro-3-methyl-2- pentenoates ($\text{7a,b}$). Since these compounds could not be hydrogenated to the desired alkyl 2-bromo-4-fluoro-3-methylpentanoates ($\text{8a,b}$), another route was taken. The esters $\text{5a–d}$ were hydrogenated to alkyl 4-fluoro-3- methylpentanoates ($\text{11a–c}$) which were converted to their carbanions. Treatment with bromine gave esters $\text{8a–c}$, and iodine gave alkyl 4-fluoro-2-iodo- 3-methylpentanoates ($\text{12a,b}$). Esters $\text{8a–c}$ and $\text{12a,b}$ were converted to alkyl 2-azido-4-fluoro-3-methylpentanoates ($\text{13a–c}$) whose hydrogenation gave alkyl 2-amino-4-fluoro-3-methylpentanoates ($\text{14a–c}$). Hydrolysis afforded γ-fluoroisoleucine ($\text{1}$).     

Chiral synthesis of statine

Statine ($\text{8a}$) has been obtained in high enantiomeric purity as its N-Boc-ethyl ester ($\text{8b}$) in a chiral synthesis. The sequence involves the enantio- and erythro-selective aldol condensation of N-Boc-L-leucinal ($\text{5}$) with (S)-4-(1-methylethyl)-3-[(methylthio)acetyl]-2-oxazolidinone ($\text{1}$) via the boron enolate, followed by desulfurization and saponification in ethanol, according to the methodology of Evans.     

Backbone rearrangements of methyl (-)-kaur-9(11)-en-19-oate and its epoxide: structures of two diterpenes of a new skeletal type

cleavage of the epoxide ($\text{2}$) of methyl (-)-kaur-9(11)-en-19-oate ($\text{1b}$) with boron trifluoride-ether in benzene and in acetic anhydride yielded ($\text{3a}$) and ($\text{3b}$), respectively. On epoxidation with $\text{m}$-chloroperbenzoic acid in the presence of $\text{N}$-nitrosomethyl urea, ($\text{1b}$) suffered a backbone rearrangement to form ($\text{6}$).     

Synthesis of oxazolidin-2-ones using carbonate ion on a polymeric support

Through the insertion of a carbon dioxide molecule, the oxazolidin-2-ones ($\text{5a}$) and ($\text{5b}$) were prepared by treataent of the salts ($\text{4a}$) and ($\text{4b}$) with carbonate anion on polymeric support. The hydrolysis under basic conditions of ($\text{5a}$) and ($\text{5b}$) afforded the erythro-3-amino-1,2-diols ($\text{6a}$) and ($\text{6b}$) which were fully acetylated: the 2-amino-2-deoxyerythritol derivative ($\text{7b}$) was obtained in 91% yield.     

Acid catalyzed isomerization of bicyclic alkenes: a facile betweenanene synthesis

Isomerization of $\text{cis}$-bicyclo[10.8.0]eicos-1(12)-ene ($\text{1a}$) and $\text{cis}$-bicyclo[10.10.0]docos-1(12)-ene ($\text{1b}$) to [10.8]- and [10.10]betweenanene ($\text{2a}$ and $\text{2b}$) has been effected by sulfuric acid. In both cases, the betweenanene isomers were found to predominate at equilibrium (70/30 $\text{2a}$/$\text{1a}$ and 95/5> $\text{2b}$/$\text{1b}$).     

A novel synthesis of (-)-carpetimycin A

A stereoselective synthesis of the known synthetic intermediate ($\text{13}$) for (-)-carpetimycin a ($\text{1}$) has been achieved starting from the monocyclic β-lactcon ($\text{8b}$) by the novel use of the direct aldol condensation of $\text{8b}$ with acetone via the titaniun enolate.     

The resolution of racemic 2-alkyl-1-aminocyclopropane-1-carboxylic acids

Practical procedures for the resolution of racemic modification of (1$\text{R}$, 2$\text{S}$)-and (1$\text{S}$, 2$\text{R}$)-1-amino-2-ethylcyclopropane-1-carboxylic acid $\text{1a}$,$\text{b}$,(1$\text{R}$, 2$\text{S}$)- and (1$\text{S}$, 2$\text{R}$)-1-amino-2-methylcyclopropane-1-carboxylic acid $\text{2a}$,$\text{b}$, and (1$\text{R}$, 2$\text{R}$)- and (1$\text{S}$, 2$\text{S}$)-1-amino-2-methylcyclopropane-1-carboxylic acid $\text{3a}$,$\text{b}$ are described; the structures as $\text{1a}$,$\text{2a}$, and $\text{3a}$ were confirmed by X-ray-crystallographic methods.     

Aromatisierung von cytclohexenon-derivaten über selenorganische zwischenstufen

Reaction of the hydroaromatic compounds ($\text{1a}$) and ($\text{3a}$) with lithium-diisopropylamide followed by phenylselenenyl chloride gives the selenides ($\text{1b}$) and ($\text{1c}$) resp. ($\text{3b}$), which form exclusively the phenols ($\text{4}$) resp. ($\text{6}$) after oxidation with 3-chloroperbenzoic acid in the presence of 3,5-dimethoxyaniline ($\text{7a}$).     

Stereoselektive synthese von α-glucosiden mit 1,1′ -diacetal-struktur

Reaction of ($\text{1b}$) and ($\text{1d}$) with the acetal ($\text{2a}$) in presence of trimethylsilyl trifluoromethanesulfonate at ?70° C gives the α-glucosides ($\text{3a}$) and ($\text{4a}$), whereas ($\text{1a}$) and ($\text{1c}$) lead to the β-glucosides ($\text{4c}$) and ($\text{4b}$). At 0° C reaction of ($\text{1a}$) with the acetals ($\text{2b-g}$) gives exclusively the α-glucosides ($\text{3b-g}$).     

Photoreactions of 2,3-diazatetracyclo[5.3.1.04,11.06,8]undeca-2,9 dienes ; the retro-1,3-dipolar cycloadditions and the nitrogen extrusion reactions

The photochemical reactions of tetracyclic azo compounds ($\text{1a–b}$) giving $\text{5a–b}$ and $\text{8a–b}$via diazoethane derivatives ($\text{6a–b}$) were investigated in addition to the nitrogen extrusion reactions leading to tetracyclo[4.3.0.0^2,9.05,7nonenes ($\text{4a–b}$).     

An efficient synthesis of optically pure anthracyclinone intermediates by the novel use of microbial reduction

Reduction of the racemic α-hydroxy ketones((±)-$\text{3a,b}$) with fermenting baker's yeast followed by fractional recrystallization and oxidation was found to readily afford optically pure anthracyclinone intermediates((R) (?)-$\text{3a,b}$ and their partially optically active antipodes ((S)(+)-$\text{3a,b}$). The useless enantiomers ((S)(+)-$\text{3a,b}$ and diastereomeric $\text{vicinal}$-diols((+)- $\text{5a,b}$) could be recycled to (±)-$\text{3a,b}$ and the achiral ketones($\text{6a,b}$) by racemization and oxidative cleavage, respectively.     

Acid-catalysed reactions of 3,5-dialkyl-spiro[2.5]Octa-2,5-dien-4-ones

Acid-catalysed ring opening of the spirodienones ($\text{2a}$) and ($\text{2b}$) using p-toluene-sulphonic acid affords the styrène derivatives ($\text{3a}$) and ($\text{3b}$), while treatment with acetic anhydride/H₂SO₄ affords the furan derivatives ($\text{4a}$) and ($\text{4b}$).     

Diborane as a reducing agent - VI the novel reduction of indole-1-carboxaldehydes to 1-methyl- indoles,di(indolyimethyl) ethers and indolylmethyl indolines

Reduction of the indole-1-carboxaldehydes ($\text{1a}$-$\text{1f}$) with borane /THF gives the 1-methylindoles ($\text{4}$) in 42-91-% yields together with the di(indolylmethyl)ethers ($\text{8}$), the indolyl-methyl indolines ($\text{7}$), the unsymmetric ether($\text{10}$) and the indolenine ($\text{11}$) as the minor products, except $\text{7a}$. This appears to be the first report on the formation of symmetric ethers in the borane/THF reduction of an oxygen function. The formation of $\text{7a}$ and $\text{7b}$ from $\text{1a}$ and $\text{1b}$ implies that electrophilic substitution takes place primarily at position 3 of 3-substituted indoles, $\text{1c - 1f}$ did not form the corresponding $\text{7}$ probably because of steric hindrance. These results are discussed in relation to the mechanisms of borane/THF reduction, origin of the different products and electrophilic substitution in 3-substituted indoles.     

Studies on amino acids and peptides VIII : Synthesis and crystal structure of two monothiated analogues of Boc-Gly-S-Ala-Aib-OMe

The model tripeptide Boc-Gly-S-Ala-Aib-OMe ($\text{2b}$) and the two monothiated analogues Boc-Gly(¹ψ²CSNH)-S-Ala-Aib-OMe ($\text{2c}$) and Boc-Gly-S-Ala(²ψ³ CSNH)-Aib-OMe ($\text{2a}$) were synthesized. Peptide $\text{2a}$ was obtained by thiation of $\text{1a}$ using 2,4-bis(4-methoxyphenyl)-1,3,2,4-dithiadiphosphetane 2,4-disulfide, Lawesson's Reagent (LR), followed by deprotection of the Boc group and coupling with Boc-Gly-OH. Thiation of $\text{2b}$ with LR regiospecifically transformed the protected tripeptide to the monothiated analogue $\text{2c}$. X-Ray diffraction analysis showed that the type-III β-turn formed by the reference peptide $\text{2b}$ is preserved in the monothiated analogue $\text{2a}$; conversely,the structure of the isomeric tripeptide $\text{2c}$ is partially extended.     

Conjugative cycloaddition of N-chlorosulfonyl isocyanate across vinylcyclopropane system. A new pathway towards macro-heterocycles

trans- -Isopropenyl-4-methylene-spiro[2.x]alkanes ($\text{4a}$ and $\text{4b}$) react at 0°C with CSI to give as major products the trans bicyclic cycloazanondienones ($\text{12a}$-$\text{12b}$) and as the minor products bicyclodihydro-azepinones ($\text{11a}$ and $\text{11b}$), and the respective cis isomer of bicyclic cycloazanondienones ($\text{13a}$ and $\text{13b}$).     

Amino substituted 1-oxa-3-azabutatrienium salts: preparation, structure and reaction with carbonyl compounds

N,N-Dimethylformamide ($\text{4a}$) and N,N-dimethylpivalamide ($\text{4b}$) react with carbonyl chloride isocyanate ($\text{5}$) in the presence of antimony pentachloride to afford the amino substituted 1-oxa-3-azabutatrienium hexachloroantimonates $\text{6a}$,$\text{b}$. An X-ray diffraction analysis of $\text{6a}$ confirms the proposed structure. The heterocumulenes $\text{6a}$,$\text{b}$ react with aldehydes, ketones and tertiary carboxamides to give the amino substituted 2-azaallenium salts $\text{13a}$-$\text{O}$ in high yields.     

The clemmensen reaction of tigogenin. A reinvestigation

The reaction of tigogenin ($\text{1b}$) with amalgamated zinc yields tetrahydrotigogenin ($\text{2b}$) and the furostan $\text{3}$. While $\text{2b}$ undergoes acid catalyzed elimination to give the rearranged product $\text{7}$, $\text{3}$ spontaneously decomposes to a mixture of $\text{4}$ and $\text{5}$.     

Biomimetic synthesis of (±) panacene

(±) Panacene $\text{1a}$ and (±) 1-epibromopanacene $\text{1b}$ have been synthesized by a biomimetic brominative cyclization of hydroxyenyne $\text{4}$.