Chemistry and Structure of Diterpene Compounds of the Kaurane Series: VI. Isosteviol Esters

Esterification with alcohols and diols of (4,8,13)-13-methyl-16-oxo-17-norkaurane-18-carboxylic acid chloride prepared by treatment of the acid (isosteviol) with thionyl chloride yields the corresponding esters. The molecular and crystal structures of a series of esters were determined by single crystal X-ray diffraction. The diethylene glycol diester in the crystal has a tweezer structure with an intramolecular cavity. The supramolecular structure of some isosteviol derivatives in the crystal is characterized by alternation of lipophilic and hydrophilic regions.     

Chemistry and Structure of Diterpene Compounds of the Kaurane Series: IX. Electrochemical Reactions of Isosteviol and Its Derivatives

The keto group in (4,8,13)-13-methyl-16-oxo-17-norkaurane-18-carboxylic acid (isosteviol) is not polarographically reduced in DMF. Isosteviol methyl ester and oximes, too, are not reduced under these conditions. Isosteviol oxime is oxidized electrochemically or with lead dioxide, yielding iminoxyl radical.     

Chemistry and Structure of Diterpene Compounds of the Kaurane Series: VIII. Azomethines Derived from Isosteviol

(4,8,13)-13-Methyl-16-oxo-17-norkaurane-18-carboxylic acid (isosteviol) and its methyl ester were reacted with benzylamine and hydroxylamine to obtain the corresponding E-stereoisomeric 16-ketimines. Isosteviol benzylimine and oxime form individual 1:1 H-bonded complexes with methanol and water, respectively.     

Chemistry and Structure of Diterpene Compounds of the Kaurane Series: VII. Chiral Complexes of Isosteviol with Aromatic Compounds

(4,8,13)-13-Methyl-16-oxo-17-norkaurane-18-carboxylic acid (isosteviol) forms with aniline, dimethylaniline, and toluene individual 2:1 molecular complexes whose crystals are isostructural. According to X-ray diffraction data, the supramolecular crystal structure of these complexes is formed by chiral double helices with a 4₃ screw axis, consisting of isosteviol molecules. The strands of the helices are linked together by intermolecular hydrogen bonds involving the carboxy and carbonyl groups of two isosteviol molecules of neighboring helices. In their turn, the two hydrogen-bonded isosteviol molecules form head-to-tail pseudocage dimers. The aromatic guests occupy fairly large cavities between the strands of isosteviol helices.     

Chemistry and Structure of Diterpene Compounds of the Kaurane Series: IV.1 Acylation of Reduction Products of the Isosteviol Keto Group

Acetylation with acetic anhydride of (4,8,13)-16-hydroxy-13-methyl-17-norkaurane-18-carboxylic acid and its methyl ester, obtained by reduction of isosteviol and (4,8,13)-18-methoxycarbonyl-13-methyl-16-oxo-17-norkaurane, respectively, gives rise to (4,8,13)-16-acetoxy-13-methyl-17-norkaurane-18-carboxylic acid and (4,8,13)-16-acetoxy-18-methoxycarbonyl-13-methyl-17-norkaurane. The molecular and crystal structures of the compounds were established by X-ray diffraction.     

Chemistry and Structure of Diterpenoids: X. Isosteviol Amides

Acylation of amino alcohols with isosteviol chloride, depending on the reactant ratio, leads to formation of either bis-isosteviol derivatives or N-acylation products. Reactions of aromatic diamines with 2 equiv of isosteviol chloride give the corresponding N,N′-bis(isostevioyl) derivatives.__________Translated from Zhurnal Obshchei Khimii, Vol. 75, No. 2, 2005, pp. 276–281.Original Russian Text Copyright © 2005 by Al’fonsov, Kataev, Strobykina, Korochkina, Kovylyaeva, Bakaleinik, Beskrovnyi, Gubaidullin, Litvinov, Musin.For communication IX, see [1].     

Synthesis and Crystal Structure of Isosteviol Derivatives

Isosteviol (ent-16-ketobeyeran-19-oic acid, I) is a tetracyclic diterpenoid with a beyerane skeleton obtained by acid hydrolysis of stevioside.1 Several tetracyclic diterpenoids, specially the kaurenes, have important biological activities. Recent studies on the microbial transformation of isosteviol have revealed that it is metabolized by Cunninghamella bainieri, Actinoplanes sp., Mucor recurvatus, and Cunninghamella blackesleeana to yield five new metabolites.2 The hydroxylation pattern of these bioactive compounds may influence their binding on to the receptors, as was proposed for the Rabdosia diterpenoids. Therefore, the introduction of hydroxyl groups or unsaturated bonds in saturated and non-hydroxylated diterpenoids, like isosteviol, may enhance existing properties or lead to new biological activities. Although some beyeranes have been subjected to biotransformations by fungi,4 there are few report in the literature related the chemical transformation of Isosteviol. In the present study, we try to develop the chemical transformation of isosteviol and other beyeranes in order to obtaining some bioactive compounds with beyerane skeleton. Seven isosteviol derivatives, Ⅱ-Ⅷ, were therefore synthesized and characterized. The X-ray crystal strcture of H(R = H) was also determined.     

Clerodane and ent‐Kaurane Diterpene Glycosyl and Glycoside Derivatives from the Leaves of Casearia sylvestris

Five new clerodane diterpene glycosyl derivatives, caseariasides A–E ( 1 – 5 , resp.) and three new ent‐kaurane diterpene glucosides, sylvestrisides C–E ( 6 – 8 , resp.) were isolated from the leaves of Casearia sylvestris. Their structures were determined on the basis of chemical and spectroscopic analyses.     

Homonuclear Selective One-Dimensional Gradient NMR Experiments in the Structure Determination of Natural Diterpene Derivatives

Summary.  The solution structure of two natural diterpene derivatives, the secondary metabolites esulatin-A and esulatin-B of Euphorbia esula, was investigated by homonuclear NMR experiments. Since the spectral dispersion of the ¹H NMR spectra at 500 MHz was sufficient to separate several skeletal protons of the title compounds, they were selectively excited with a double pulsed field gradient spin-echo (DPFGSE) sequence using 180°Gaussian pulses sandwiched between sine shaped gradients. With the use of selective excitation, scalar as well as dipolar interactions of the selected spins were monitored through one-dimensional (1D) COSY, TOCSY, and NOESY experiments. The chemical shifts of the coupling partners could be accurately extracted from the 1D COSY and TOCSY spectra recorded with high digital resolution. The selective TOCSY experiment provided an excellent opportunity to identify spins belonging to the same scalarly coupled spin system. The solution state conformation was investigated by selective gradient enhanced NOESY experiments. Proton–proton distances were evaluated from the cross-relaxation rates obtained from a quantitative analysis of the NOESY spectra recorded with different mixing times. The NMR derived distances were compared to the results of solid state X-ray diffraction measurements. Corresponding author. E-mail: pforgo@chem.u-szeged.hu Received November 21, 2001. Accepted (revised) January 9, 2002     

A New ent‐Kaurane Diterpene from Stems of Alibertia macrophylla K. Schum. (Rubiaceae)

Phytochemical investigations of the stems of a specimen of Alibertia macrophylla led to the isolation and characterization of the new diterpene ent‐kaurane‐2β,3α,16α‐triol ( 1 ), along with triterpenes 2 – 8 , iridoids 9 – 12 , and phenolic acids 13 – 15 . The structure of 1 was established based on spectroscopic studies (¹H‐ and ¹³C‐NMR, IR, and HR‐ESI‐MS). This is the first report of the isolation of a diterpene from the Alibertia genus in Rubiaceae.     

Chemistry of Succinyl Succinic Acid Derivatives. Part V. On the transesterification of succinyl succinates

The unique stabilization of the ester link in dialkyl succinyl succinates is explained and a facile route to known as well as to hitherto inaccessible succinyl succinates is suggested. New representatives of this series are described.     

Cyclic Phosphorus(V) Compounds: Phosphazanes and Anhydrides

Abstract

³¹P n.m.r. has been extensively used to study the preparation and reactions of cyclic phosphorus-(V) compounds containing P-N-P and P-O-P linkages. Michaelis “Oxyphosphazobenzolchlorid”,[C₆H₅NPOCl]_n has been shown by ³¹P n.m.r. and mass spectroscopy to be the trimer (n=3), not the dimer as proposed by Michaelis. The competing reactions of aniline hydrochloride and POCl₃ to form the dimer (two isomers cis- and trans-) and the trimer have been elucidated. With PSCl₃ only the dimer [C₆H₅NPSCl]₂ is formed (both isomers).     

Divergent Synthesis of γ-Amino Acid and γ-Lactam Derivatives from meso-Glutaric Anhydrides

The first divergent synthesis of both γ-amino acid and γ-lactam derivatives from meso-glutaric anhydrides is described. The organocatalytic desymmetrisation with TMSN₃ relies on controlled generation of a nucleophilic ammonium azide species mediated by a polystyrene-bound base to promote efficient silylazidation. After Curtius rearrangement of the acyl azide intermediate to access the corresponding isocyanate, hydrolysis/alcoholysis provided uniformly high yields of γ-amino acids and their N-protected counterparts. The same intermediates were shown to undergo an unprecedented decarboxylation–cyclisation cascade in situ to provide synthetically useful yields of γ-lactam derivatives without using any further activating agents. Mechanistic insights invoke the intermediacy of an unconventional γ-N-carboxyanhydride (γ-NCA) in the latter process. Among the examples prepared using this transformation are 8 APIs/molecules of considerable medicinal interest.