Structure and absolute configuration of 3-alkylpiperidine alkaloids from an Indonesian sponge of the genus Halichondria

Chemical analysis of an Indonesian sponge sample has provided three new 3-alkylpiperidine alkaloids, tetradehydrohaliclonacyclamine A, its mono-N-oxide derivative, and a 2-epi isomer. The absolute structure of tetradehydrohaliclonacyclamine A has been established by X-ray crystallography from anomalous dispersion effects using Cu radiation, which determined that the absolute configuration is 2S, 3S, 7S, 9S while an HPLC study revealed that the alkaloid is enantiomerically pure.     

The absolute stereochemistry of several cis-dihydrodiols microbially produced from substituted benzenes

The absolute stereochemistry of a series of 3-substituted cis-dihydrodiols obtained by microbial oxidation of toluene, ethylbenzene, chlorobenzene, and biphenyl has been assigned from chemical and spectrophotometric studies. ?-Halogenated toluenes also have been investigated as substrates in these oxidations, and the corresponding cis-dihydrodiols isolated. Implications from the observation that some of the cis-dihydrodiols are racemic are discussed. Oxidation of an olefin, (±)-3-methylcyclohexene, by these microorganisms leads only to cis-diols whose absolute stereochemistry about the hydroxyl-bearing carbons is the same as that found for the cis-dihydrodiols formed from the aromatic substrates.     

Determination of absolute configuration using vibrational circular dichroism spectroscopy: phenyl glycidic acid derivatives obtained via asymmetric epoxidation using oxone and a keto bile acid

The (+)-enantiomers of the o-Br, m-F and p-CH₃ derivatives of trans phenyl glycidic acid have been obtained from the corresponding trans cinnamic acid derivatives using Oxone and the tri-keto bile acid dehydrocholic acid. Vibrational circular dichroism (VCD) spectroscopy of their methyl esters has been used to determine their absolute configurations. In each case, the absolute configurations of both methyl ester and parent acid were shown to be (2S,3R)-(+)/(2R,3S)-(−).     

Lipase-catalyzed resolution of 5-acetoxy-1,2-dihydroxy-1,2,3,4-tetrahydronaphthalene. Application to the synthesis of (+)-(3R,4S)-cis-4-hydroxy-6-deoxyscytalone, a metabolite isolated from Colletotrichum acutatum

(+)-cis-4-Hydroxy-6-deoxyscytalone, a natural product bio-synthesized by Colletotrichum sp., has been prepared and its absolute configuration confirmed as 3R,4S, the key step being a kinetic racemic resolution of a cis-diol easily obtained from commercial 1,2,3,4-tetrahydronaphthalen-1,5-diol. Four lipases and different reaction conditions were tested in order to obtain the best yield and enantiomeric excess. Confirmation of absolute configuration was made by NMR using a single-derivatization low-temperature procedure and MPA as the auxiliary reagent.     

Synthesis of all 7αH-guaia-4,11-dien-3-one diastereomers from (+)-dihydrocarvone

All four 7αH-guaia-4,11-dien-3-one diastereomers have been synthesized from the common intermediate 1αH,10α-acetoxy-7αH-guaia-4,11-dien-3-one obtained from (+)-dihydrocarvone. The spectral features of the four diasteromers have been correlated and the structure and absolute configuration of 1βH,10βH,7αH-guaia-4,11-dien-3-one isolated from Pleocarphus revolutus has been confirmed.     

First total synthesis of (+)-Vedelianin, a potent antiproliferative agent

The total synthesis of (+)-vedelianin has been accomplished in 18 steps from vanillin. Preparation of a key intermediate in nonracemic form through a Shi epoxidation has allowed determination of the absolute stereochemistry of the natural product as the (2S,3R,4aR,9aR)-isomer.     

A convenient method for the assignment of the absolute configuration to cyclic amines

We have assigned the absolute configuration to trans-2,5-dimethylpyrrolidine and trans-2,6-dimethyl-piperidine through radical chlorination in ω-1 position of optically active amines, 2 and 5, of known absolute configuration, followed by cyclization. CD curves of 1f and 4g derivatives indicate that the reaction is stereospecific. The absolute configuration of trans-2,5-dimethyl-Δ³-pyrròline has also been determined.     

Novel stereocontrolled synthesis of the tricyclic lactone (1R,3R,6R,9S)-6,9-dimethyl-8-oxo-7-oxatricyclo[4.3.0.03,9]nonane

The stereocontrolled synthesis of (1R,3R,6R,9S)-6,9-dimethyl-8-oxo-7-oxatricyclo[4.3.0.0^3,9]nonane 1 from (R)-(−)-carvone has been accomplished by application of a 13-step sequence with 12% overall yield. The absolute stereochemistry of the unsaturated acid 8a has been established by X-ray analysis of the chiral amide 8c.     

The absolute molecular structure of (−)-podopetaline

X-ray analysis of crystals of podopetaline hydrobromide, C₂₀H₃₃N₃·HBr, has established the absolute structure of podopetaline, an alkaloid from Podopetalum ormondii F. Muell. The crystals are orthorhombic, with unit cell dimensions, a = 6·619, b = 10·907, c = 26·806 Å, Z = 4, the space group being P2₁2₁2₁. The intensity data were measured with CuKα radiation on a single-crystal diffractometer. The crystal structure was solved by the heavy atom method and refined by difference and least-squares procedures to a final R index of 0·069 for the 849 observed terms. The absolute chirality has been defined by Bijvoet's technique. Podopetaline (I) therefore provides an absolute chirality reference for Ormosia alkaloids which was not previously available.     

Asymmetric synthesis of (−)-chicanine using a highly regioselective intramolecular Mitsunobu reaction and revision of its absolute configuration

First asymmetric synthesis of (−)-chicanine has been accomplished in 14 steps by employing the Evans asymmetric syn-selective aldol reaction, diastereoselective hydroboration and an regioselective, intramolecular Mitsunobu etherification. The absolute configuration of (+)- and (−)-chicanine has been revised to 2R,3S,4R,5R and 2S,3R,4S,5S, respectively, through CD analysis.     

Stereoselective total synthesis of achaetolide and reconfirmation of its absolute configuration

The stereoselective total synthesis of achaetolide 1 has been achieved and its absolute stereochemistry has been reconfirmed to be 3S,6R,7S,9R configuration. Keck allylation, Sharpless asymmetric dihydroxylation, and ring closing metathesis are the key steps involved in the target synthesis.     

The absolute molecular structure of Hodgkinsine

Preliminary crystallographic analysis of crystals of the respective benzene and bromobenzene adducts of hodgkinsine, an alkaloid from Hodgkinsonia frutescens F. Muell. (family Rubiaceae), together with mass spectral evidence suggested a formulation for hodgkinsine based on three N-methyltryptamine units. X-ray analysis of crystals of the trimethiodide monohydrate, C₃₃H₃₈N₆.3CH₃I.H₂O, has defined the absolute molecular structure of hodgkinsine. These crystals are monoclinic belonging to the space group P2₁, with a = 12·779, b = 13·923, c = 11·190 Å, β = 107·78°, Z = 2. The crystal structure has been solved from data collected with CuKα radiation on a single-crystal diffractometer and refined by least-squares procedures from intensity data re-collected with MoKα radiation. The absolute chirality was defined by Bijvoet's technique. The molecular structure of hodgkinsine is given as I. Two of the N-methyltryptamine units T″ and T″' are in the same configuration while T′ is in the opposite. The CD spectrum of hodgkinsine is discussed in relation to these units of different chiralities.     

Biphenyl-cis-diol chemistry to access enantiopure aryl-substituted organoiron complexes

The endo face selectivity of the complexation of the biologically derived 3-phenyl-1,2-dihydroxycyclohexa-3,5-diene ligand has been proved by an X-ray crystallographic study of the enantiopure (1R,2S,3S) η⁴ tricarbonyliron complex, and the correlation between the absolute configuration of the complex and its circular dichroism curve has been established to provide a basis on which to assign absolute configurations in the synthetically important [‘-(Ar)CCH-CHCH-’]Fe(CO)₃ series.     

Chemical studies of marine invertebrates—XI : Sinulariolide,a new cembranolide diterpene from the soft coral Sinularia flexibilis (coelenterata,octocorallia, alcyonacea)

Sinulariolide, a novel diterpene lactone has been isolated from the alcyonarian Sinularia flexibilis. Its structure [1] has been determined by using spectroscopic and chemical methods. Its relative and absolute configuration was established by X-ray diffraction as depicted in 10.     

Celogentin K, a new cyclic peptide from the seeds of Celosia argentea and X-ray structure of moroidin

A new cyclic peptide with a 3-hydroxyoxindole ring, celogentin K (1), has been isolated from the seeds of Celosia argentea and the structure including its absolute stereochemistry was assigned by using extensive NMR, MS/MS, and CD spectra. The stereostructure of a known related bicyclic peptide, moroidin (2), was confirmed by a single crystal X-ray diffraction analysis.     

The absolute configuration and circular dichroism of (+)-(1,5)-diamino-triptycene

The absolute configuration of(+)-(1,5)-diamino-triptycene has been determined by calculation of the CD spectrum of the molecule and comparison with the experimental results of Tanaka et al.⁴ To achieve this the exciton theory of Weigang and Nugent³ has been extended to include terms representing the retardation of the electro-magnetic wave in the chromophores. The final results of the present study are in contradiction with those of Tanaka et al.^4a,b,c     

Absolute configuration of diterpenoid diacylglycerols from the Antarctic nudibranch Austrodoris kerguelenensis

The R absolute configuration at C-2′ of the glyceryl moiety of the natural diterpenoid 1,3-glyceryl esters 1 and 2 has been established by applying the modified Mosher method. These esters have been isolated, together with the corresponding 1,2-derivatives (3 and 4), from different collections of the Antarctic dorid nudibranch Austrodoris kerguelenensis. Surprisingly, such a configuration is opposite to that of all marine terpenoid diacylglycerols so far reported. Compounds 1 and 3 are new natural products closely related to austrodorin 5, already described from the same species.     

Optically active palladacycles containing imines derived from 1-(1-naphthyl)ethylamine: new resolving agents for P-chiral phosphines

The synthesis of the new palladium metallacycles containing imines derived from 1-(1-naphthyl)ethylamine is reported. These new organometallic complexes have been used to resolve the P-chiral ligand benzylcyclohexylphenylphosphine. The absolute configuration of (R_C,S_P)-[PdCl{2-[HCN-CH(Me)C₁₀H₆]-3-ClC₆H₃}(PBzCyPh)] has been determined by single crystal X-ray analysis.     

Synthesis of the core ring system of awajanomycin from N-Boc-3-methoxycarbonyl-2-pyridinone

Awajanomycin, which was isolated from marine-derived fungus, possesses unique structural features and cytotoxic activity against A549 cells. Due to its unique structure, no total synthesis has yet been reported, and neither the relative stereochemistry nor the absolute configuration has been determined. We report the synthesis of the core ring system of awajanomycin, which includes: (i) regioselective addition of the acetate unit onto C4-position of N-Boc-3-methoxycarbonyl-2-pyridinone; (ii) stereoselective installation of a hydroxyl group on C3-position; and (iii) stereo- and regioselective epoxide-opening reaction by Me₃Al.     

Synthesis of 2-(1-aminocyclopropyl)pyrrolidine-3,4-diol derivatives applying titanium-mediated reaction conditions

The titanium-mediated cyclopropanation reaction using Ti(OⁱPr)₃Me/EtMgBr/BF₃·OEt₂ has been applied to various 2-cyanopyrrolidines for the synthesis of functionalized 2-(1-aminocyclopropyl)pyrrolidine-3,4-diol derivatives (dideoxyiminoalditols). Under the same experimental conditions the trans-5-azidomethyl-2-cyanopyrrolidine derivative was not cyclopropanated but reduced into the corresponding 5-amino-2-cyano derivative. After polyol deprotection 2-(1-aminocyclopropyl)pyrrolidine-3,4-diols were obtained and their inhibitory activity towards 13 glycosidases has been evaluated. (2S,3S,4R,5S)-2-(1-Aminocyclopropyl)-5-methylpyrrolidine-3,4-diol (38), which has the same absolute configuration as l-fucose, is a moderate (IC₅₀=44 μM), but selective, inhibitor of α-l-fucosidase from human placenta.