First enantioselective synthesis of (+)-quinolizidine 207I: determination of the absolute stereochemistry

First enantioselective synthesis of quinolizidine 207I has been achieved and the absolute stereochemistry of natural quinolizidine 207I was determined to be 1S,4S,10S by the present chiral synthesis using GC analysis with β-dextrin chiral column on co-injection with racemate.     

First stereoselective total synthesis of decytospolides A and B

The first stereoselective total synthesis of decytospolides A and B has been accomplished starting from n-hexanal. The key steps involved in this synthesis are Horner-Wittig reaction, Sharpless asymmetric epoxidation, and oxa-Michael reaction.     

Enantioselective syntheses of two 5, 9E diastereomers of 223V, an alkaloid from the poison frog Dendrobates pumilio

Enantioselective syntheses of two 5, 9E diastereomers (1 and 2) of 223V (3) are described. Neither corresponded on GC-MS and GC-FTIR analyses to alkaloid 223I, previously tentatively proposed to be a 5,8-disubstituted indolizidine of the unusual 5, 9E relative stereochemistry. Synthetic (−)-(5, 9Z)-5-n-propyl-8-n-butylindolizidine (3) corresponds on GC-MS and GC-FTIR analyses to the natural indolizidine 223V found in a pumilio from ‘Split Hill’, Panama.     

Tonkinensines A and B, two novel alkaloids from Sophora tonkinensis

Tonkinensines A (1) and B (2), two novel cytisine-type alkaloids that feature the skeleton with a linkage to pterocarpan, were isolated from the roots of Sophora tonkinensis. Their structures and absolute configurations were elucidated by spectroscopic methods, especially X-ray crystal diffraction and CD spectral analysis. The proposed biosynthetic pathway was also discussed. Both 1 and 2 were tested in HeLa and MDA-MB-231 tumor cell lines, and compound 2 showed moderate cytotoxic activity.     

Synthesis of the FG ring fragment of pectenotoxins 1-9

The synthesis of the FG ring fragment common to pectenotoxins 1-9 is reported. The successful, convergent synthesis relied on high yielding routes to access two key intermediates; aldehyde 1 and phosphonium salt 2. A Z-selective Wittig reaction gave access to advanced linear precursor 3, which was converted to FG ring fragment 4 using two sequential cyclization reactions.     

An efficient synthesis of d-ribo- and l-lyxo-phytosphingosine from d-tartaric acid

The preparations of d-ribo- and l-lyxo-phytosphingosines (1, 2) are described. Chelation-controlled addition of tetradecylmagnesium bromide to pentylidene-protected d-threitol aldehyde 6 afforded the key intermediate tetrol 7, providing the desired l-lyxo stereochemistry of phytosphingosine. Inversion at C4 of intermediate 7 provided the d-ribo stereochemistry.     

Disparate orientation of [1]rotaxanes

A novel [1]rotaxane 2 has been synthesized employing a 4-methyl-benzenesulfonyl and an azobenzene modified β-cyclodextrin (β-CyD) at the 2 position, through self-inclusion complexation and Suzuki-coupling capping in aqueous solution. Disparate absorption, induced circular dichroism (ICD) properties from its isomer [1]rotaxane 1, prepared from the isomeric β-CyD modifier at the 6 position, and the photoisomerization of [1]rotaxane 2 were thoroughly investigated.     

The enantioselective synthesis of poison-frog alkaloids (−)-203A, (−)-209B, (−)-231C, (−)-233D, and (−)-235B″

The enantioselective synthesis of indolizidines (−)-203A, (−)-209B, (−)-231C, (−)-233D, and (−)-235B″ has been achieved and the absolute stereochemistry of both indolizidines 203A and 233D was established as 5S,8R,9S. The relative stereochemistry of natural 231C was established by the present asymmetric synthesis.     

Stereoselective synthesis of l-isonucleosides

l-Isonucleosides 17 and 19 were stereoselectively synthesised from (S)-glycidol by two different procedures. The key step was the synthesis of a chiral dihydrofuran which was carried out by oxidation/elimination of 8 and by ring-closing metathesis of diene 10. The procedure can be applied to the synthesis of both enantiomers.     

Stereo-conserved synthesis of syn-diarylheptanoids, active principles of Zingiber, starting from d-glucose

A highly efficient and stereo-controlled synthetic strategy has been developed to access syn-diarylheptanoids, for example, 2,3, 4, and 5b starting from d-glucose as a chiral pool. The 3-(R), 5-(S)-syn-diol stereochemistry present in these heptanoids was obtained after conserving C2 and C4 stereochemistry of d-glucose during the course of synthetic transformation. The key features of this synthetic strategy include: (i) conversion of d-glucose to a known chiral template 6 armored with the required 1,3-syn-diol stereochemistry as well as two terminal aldehyde functionalities for building up customized ‘diaryl wings’; (ii) conversion of 6 to 7 via an initial Wittig olefination at the C5-aldehyde; (iii) use of the hemiacetal 7 as a common intermediate to obtain the individual heptanoids via a second Wittig reaction at its anomeric center using appropriately chosen ylides.     

Organofluorine compounds and fluorinating agents : Part 28. New perfluoroalkyl substituted chiral mesogens

The perfluorohexyl-aryl-thioethers 3 and 4, building blocks for the synthesis of the chiral target mesogens 12-15, were prepared by dithionite-mediated S-perfluoroalkylation of the p-substituted thiophenols 1 and 2. The phenolic HO group of 3 was O-glucosylated with pentaacetyl-d-glucopyranose to 5 followed by deacetylation forming the tetrol 6 and by acetalizing with 4-(4-perfluorohexylsulfanyl-benzoyloxy)-benzaldehyde-dimethylacetal (8) generating the dihydroxy-intermediate 9. The latter contains two perfluorohexylthio chains. Alternatively, the dimethylacetal 8 was linked to p-octylphenyl-β-d-glucopyranoside (10) giving the mixed octyl/perfluorohexyl substituted p-octylphenyl-4,6-O-[4′-(4″-perfluorohexylsulfanyl)-benzoyloxy]-benzylidene-β-d-glucopyranoside (11). Compound 8 was obtained via esterification of 4 with p-hydroxy-benzaldehyde to 4-(4-perfluorohexylsulfanyl-benzoyloxy)-benzaldehyde (7). Finally, the diols 9 and 11 were dehydroxylated to 12 and 13 followed by hydrogenation yielding 14 and 15, respectively. Tetrol 6, diols 9, 11 and the non-amphiphilic compounds 7, 12-15 are thermotropic liquid crystals.     

Isochinolinio-amidate : Synthese und einige reaktionen von N-acyl- und N-sulphonyl-derivaten

Three methods have been developed for the synthesis of N-acyl- and N-sulfonyl-aminoisoquinolinium chlorides (6) and the corresponding dipolar bases (7): (1) ring closures of N-acyl- and N-sulfonyl-N-{2-[β-(2,4-dinitranilino)vinyl]benzylidene}hydrazines(5β), (2) acylation of N-aminoisoquinolinium chloride (6a) and (3) transacylations of N-(2-isoquinolinio)-ethoxycarbonylamidate (7i). IR and NMR spectra as well as some reactions of compounds 7 are discussed.     

The rearrangement of cyclopropyl chlorides to allyl chlorides : Stereospecificity in the recapture of the chloride ion

The cyclopropyl chlorides (1 and 2) rearrange on heating to give stereospecifically the allyl chlorides (3 and 4, respectively). In the presence of nucleophiles such as methoxide ion, the corresponding allyl ethers (5 and 6, respectively) are formed. Analysis of the stereochemistry of these products indicates that they are formed from the corresponding allyl chlorides (3 and 4), which are evidently the first-formed products of the reaction even in the presence of strong nucleophiles. The reaction of the allyl chlorides (3 and 4) with sodium phenylthioxide in aprotic non-polar solvents goes predominantly with retention of configuration, but in methanol is normal in giving predominantly inversion of configuration.     

Synthesis and characterisation of Pd(II) complexes with a derivative of aminoazobenzene: Dynamic H-NMR study of cyclopalladation reactions in DMF

Three new Pd(II) complexes, i.e. [PdCl₂L]₂ (A), PdCl₂L₂ (B) and [Pd(μ-Cl)(L-H)]₂ (C), each with two diethyl [α-(4-benzenazoanilino)-2-hydroxybenzyl]phosphonates (L) bound to either one or two palladium atoms, are synthesized and characterized by elemental analysis, by IR, UV-vis and solid-state ¹³C-NMR spectra. Complexes B and C are additionally characterized by ¹H-, ¹³C- and ³¹P-NMR and electrospray mass spectrometry (ESMS) studies using dimethylformamide (DMF) as a solvent. In DMF solution adducts A and B undergo spontaneous rearrangement into the cyclopalladated complex C. Dynamic ¹H-NMR study of this rearrangement as well as of the reactions of L with PdCl₂ and Na₂PdCl₄ revealed a complex equilibrium in DMF solutions and enabled the formation mechanism of all involved species to be resolved. The complex A is immediately solvolyzed producing two molecules of intermediate M [PdCl₂(L)(DMF)]. Complex M was also the first intermediate in the reaction of L with PdCl₂. Once present in concentration above 10⁻⁵ mol dm⁻³M dimerizes very fast into chloro-bridged dimer [PdCl(μ-Cl)(L)]₂ (D) which undergoes cyclopalladation and converts into the complex C. The formation of C from the intermediate D is clearly demonstrated by the concentration dependence of the cyclopalladation reaction which has order greater than one. Chloride ions, released by cyclopalladation, react with D by splitting chloro-bridge and binding to metal atoms to produce byproduct [PdCl₃(L)]⁻ (T). The same species T are formed in the reaction of L with Na₂PdCl₄ whereby a chloride ion is replaced by the ligand L. The complex B undergoes similar, but slower, solvolytic reaction producing M and L while further reaction steps are identical as in the solvolysis of A.     

New synthesis of (−)- and (+)-actinobolin from d-glucose

The total synthesis of (−)-actinobolin 2, an antipode of the natural product starting from d-glucose is described. A three-component coupling reaction of a functionalized cyclohexenone (+)-6, derived from d-glucose by way of Ferrier's carbocyclization, with vinyl cuprate and an aldehyde (R)-5 effectively constructed the carbon framework of 2 in a highly stereoselective manner. The formal synthesis of the natural enantiomer 1 from d-glucose was also achieved.     

Diastereoselective synthesis of 10b-substituted hexahydropyrroloisoquinolines from l-tartaric acid. Creation of a quaternary carbon stereocentre via N-acyliminium ion cyclization

A simple, three-step synthesis of 10b-substituted-hexahydropyrroloisoquinolines 12-17 starting from an L-tartaric acid derived imide is described. The methodology presented employs the addition of a Grignard reagent to the imide carbonyl group, followed by a one-pot acetylation-cyclization sequence. The crucial step, an acid-catalyzed carbon-carbon bond forming reaction via an N-acyliminium ion offers moderate to high stereoselectivity, which has been shown to be strongly dependent on the size of the R-substituent. The mixtures of pyrroloisoquinolines obtained can be separated as enantiomerically pure 2-silyloxy-derivatives.     

Enantiodivergent synthesis of the quinolizidine poison frog alkaloid 195C

Herein, we describe the enantiodivergent synthesis of the 1,4-cis-disubstituted quinolizidine alkaloid 195C. Although the stereoselectivity of the final hydrogenation reaction was low, we have proposed the first chiral total synthesis of both (−)- and (+)-195C as an enantiodivergent process.     

Total synthesis of actinobolin from d-glucose by way of the stereoselective three-component coupling reaction

The total synthesis of (−)-actinobolin 3, an antipode of the natural product, starting from d-glucose is described. A three-component coupling reaction of functionalized cyclohexenone (+)-6 derived from d-glucose by way of Ferrier's carbocyclization reaction, with vinyl cuprate and 2-alkoxypropanal 7 effectively constructed the carbon framework of 3 in a highly stereoselective manner. In an aldol process of the three-component coupling reaction, stereochemical control (chelation and Felkin-Anh conditions) was achieved by the choice of the protecting groups of a hydroxy function in 2-hydroxypropanal and the reaction solvents. The formal synthesis of the natural enantiomer, (+)-actinobolin 1, starting from d-glucose was also accomplished.     

Tetrahydrofuran-mediated radical processes: stereoselective synthesis of d,l-hexestrol

The highly stereoselective synthesis of d,l-hexestrol (1), an inhibitor of microtubule assembly, is developed by using, as a key step, an intermolecular coupling of Co₂(CO)₆-complexed propargyl radicals. The latter are generated by novel complementary processes involving an interaction of tetrahydrofuran with Co₂(CO)₆-complexed propargyl alcohols and cations. An isomerically pure d,l-μ-η²-[3,4-di(4-methoxyphenyl)-1,5-hexadiyne]-bis-dicobalthexacarbonyl (d,l-6) is isolated in 69-91% yield with intermolecular coupling reactions exhibiting an excellent chemo- (0.5-7%) and d,l-diastereoselectivity (90-94%). The structure of d,l-6 is determined by X-ray diffraction. The subsequent steps include BBr₃-induced demethylation of 4-methoxyaryl groups, demetalation with cerium(IV) ammonium nitrate, and hydrogenation of acetylenic termini affording d,l-hexestrol (1).     

Photochemical transformation leading to eupteleogenin—I: Introduction of epoxy-lactone system

Being interested in the photochemical reactions which are potentially applied in the biogenetic-type chemical derivations of natural products, the appropriate photochemical means have been sought to produce the 11α,12α-epoxy-13β,28-lactone moiety in the oleanane skeleton, which is one of the unique functions of eupteleogenin (2). Photooxidation of oleanolic acid (6a) in acidic medium has been undertaken and desired 11α,12α-epoxy-oleanolic lactone (12a) obtained. Erythrodiol (8a) has been submitted to photooxidation and the 11α,12α-epoxy-13β,28-oxide moiety (24a) introduced along with skeletal rearrangement affording the 11α,12α-epoxy-taraxerene derivative (25a). During photooxidation of 8a, it has been noticed that 11ξ-hydroxy-olean-12-ene derivatives (28, 42) are fairly labile, allowing the trans-formation of dihydropriverogenin A(10a) into the thermodynamically less favored isomer priverogenin B(9).