Total synthesis of (+)-massarinolin B and (+)-4-epi-massarinolin B, fungal metabolites from Massarina tunicata

The Cr(II)- and Ni(II)-mediated coupling of several tricyclic chiral aldehydes with (E)-β-iodomethacrylates (Nozaki-Hiyama-Kishi reaction) was successfully applied to the preparation of some valuable key intermediates of our synthetic strategy to the fungal metabolites (+)-massarinolin B, (+)-4-epi-massarinolin B and (+)-massarinolin C.     

Diastereoselective synthesis of homo-N,O-nucleosides

A new class of homo-N,O-nucleosides has been designed, based on the 1,3-dipolar cycloaddition of C-substituted nitrones with allyl nucleobases. The N-methyl-C-ethoxycarbonyl nitrone 1, and the C-α-silyloxymethyl-N-methyl nitrone 7 have been exploited: the stereochemical features of the obtained nucleosides are dependent on the nature of the dipole. The results obtained with DFT calculations fully agree with the experimental results and successfully reproduce the experimentally observed reversal of endo/exo selectivity for nitrones 1 and 7.     

Synthesis of (+)-anatoxin-a using enyne metathesis

Synthesis of N-tosylanatoxin-a was achieved by metathesis of enyne in cis-substituents on a pyrrolidine derivative. Metathesis reactions of enyne having terminal alkyne using various ruthenium-carbene complexes did not give a good results. However, when the terminal alkyne was protected with a TMS group, the reaction proceeded smoothly using a second-generation ruthenium-carbene complex to give the desired cyclized compound in high yield. Oxymercuration followed by Dess-Martin oxidation afforded N-tosylanatoxin-a.     

Dibutylphosphate (DBP) mediated synthesis of cyclic N,N′-disubstituted urea derivatives from amino esters: a comparative study

The N,N′-disubstituted urea derivatives such as amino acid hydantoins and dihydrouracil derivatives were prepared starting from natural and unnatural amino acid esters using dibutylphosphate (DBP). During the attempted synthesis of N-heterocycles with larger than six-membered rings containing the N,N′-disubstituted urea functionalities, three unexpected products namely squamolone, N-methyl pyrrolidine-2-one, and diketopiperazine were isolated.     

Chemoenzymatic total syntheses of the linear triquinane-type natural products (+)-hirsutic acid and (−)-complicatic acid from toluene

Total syntheses of title natural products, 1 and 2, have been achieved using the cis-1,2-dihydrocatechol 7 as starting material. Compound 7 is readily obtained in large quantity and enantiomerically pure form through the whole-cell biotransformation of toluene using the genetically engineered micro-organism Escherichia coli JM109 (pDTG601) that over-expresses the enzyme toluene dioxygenase (TDO). Three key chemical steps were employed in these syntheses, the first of which was a high-pressure-promoted Diels-Alder cycloaddition reaction between diene 8 and cyclopentenone to give adduct 9. The second key step was the photochemically promoted oxa-di-π-methane rearrangement of the bicyclo[2.2.2]octenone derivative, 18, of 9 to give 20 while the third key step was the reductive cleavage of the last compound so as to afford the linear triquinane 22. Elaboration of compound 22 to targets 1 and 2 followed conventional and/or established procedures. Single-crystal X-ray analyses were carried out on compounds 10-13, 15, 18, 24, and 34.     

Chiral self-assembly of triorganotin complexes: Syntheses, characterization, crystal structures and antitumor activity of organotin(IV) complexes containing (R)-(+)-methylsuccinic acid, (S)-(+)-methylglutaric acid and l-(−)-malic acid ligands

Six new chiral triorganotin(IV) complexes, {(R₃Sn)₂[C₃H₆(COO)₂]}_n (R = Me: 1; Bu: 2), {(R₃Sn)₂[C₄H₈(COO)₂]}_n (R = Me: 3; Bu: 4), and {(R₃Sn)₂[C₂H₄O(COO)₂]}_n (R = Me: 5; Bu: 6) have been prepared by treatment of (R)-(+)-methylsuccinic acid, (S)-(+)-methylglutaric acid and l-(−)-malic acid, with the corresponding R₃SnCl (R = Me, Bu) and sodium ethoxide in methanol. All the complexes were characterized by elemental analysis, FT-IR, NMR (¹H, ¹³C, ¹¹⁹Sn) spectroscopy and TGA. Except for 3, all of the complexes were also characterized by X-ray crystallography. The structural analyses reveal that complexes 1 and 5 have 2D network structures in which (R)-(+)-methylsuccinic acid and l-(−)-malic acid act as tetradentate ligands coordinated to trimethyltin(IV) ions. Complexes 2 and 4 have 3D metal-organic framework structures in which the deprotoned acids serve as tetradentate ligands. Complex 6 adopts a 1D zigzag chain structure and forms a 2D supramolecular framework through intermolecular C-H?O interactions. In addition, the antitumor activities of complexes 1-6 have been studied. We also have measured the specific rotation of the chiral dicarboxylic acids and the organotin derivatives.     

Diastereoselective synthesis of β-aminocyclopentene sulfonic acid via hetero Diels-Alder reaction

A new cyclopentene GABA analogue was synthesized as a conformationally rigid analogue of the epilepsy drug vigabatrin. N-Sulfinyl dienophile Diels-Alder methodology, followed by alkaline hydrolysis of the corresponding dihydrothiazine oxide, oxidation and deprotection of the amino group gave cis-4-aminocyclopent-2-ene-1-sulfonic acid. The corresponding N,N-dimethylsulfinamide was also obtained.     

Chemical modification of usnic acid 2. Reactions of (+)-usnic acid with amino acids

The condensation of amino acids with (+)-usnic acid involves the 2-positioned acetyl group of the latter and gives derivatives containing an enamine fragment. Dedicated to the memory of Academician N. N. Vorozhtsov on the 100th anniversary of his birth. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 6, pp. 1203–1205, June, 2007.     

First total synthesis of (+)-crassalactone A

A simple and highly efficient first total synthesis of cytotoxic (+)-crassalactone A starting from (R)-mandelic acid is described. The strategy involves the osmium tetroxide-catalyzed cis-hydroxylation and the stereoselective addition of ethyl lithiopropiolate to a chiral aldehyde intermediate as key steps.     

First total synthesis of (+)-viroallosecurinine

The first diastereoselective chiral synthesis of (+)-viroallosecurinine, isolated from Securinega virosa as a cytotoxic alkaloid, was achieved by using a chelation-controlled addition of an alkyne moiety to the corresponding ketone, and a ring-closing metathesis, as key reactions.     

Stereoselective synthesis of (+)-(8R,8aR)-perhydro-8-indolizidinol

A highly stereoselective total synthesis of (+)-(8R,8aR)-perhydro-8-indolizidinol is described. Key steps involved in this synthesis are diastereoselective zinc allylation, azido-olefin cyclization and reductive amination followed by cyclization which effectively constructed the indolizidine ring. This contributes a unique approach to the synthesis of indolizidine alkaloids that offers the advantages of brevity and relatively high overall yields.     

Artalbic acid, a sesquiterpene with an unusual skeleton from Artemisia alba (Asteraceae) from Sicily

From the aerial parts of Artemisia alba (Asteraceae) artalbic acid (1), a sesquiterpene with an unusual skeleton, was isolated. Its structure was elucidated on the basis of extensive proton, ¹³C and two-dimensional NMR experiments, as well as by transformation in its methyl ester derivative.     

The stereoselective total synthesis of (+)-18-(6S,9R,10R)-bovidic acid

An expedient stereoselective total synthesis of 18-carbon (+)-(6S,9R,10R)-bovidic acid, isolated from the pelage and skin of a gaur B. frontalis is described using l-proline catalysed sequential α-aminoxylation and Horner-Wadsworth-Emmons olefination of aldehyde, cross metathesis and tandem Sharpless asymmetric dihydroxylation-S_N2 cyclization reaction as the key steps.     

Chemo-enzymatic enantio-convergent asymmetric synthesis of (R)-(+)-Marmin

Asymmetric biohydrolysis of trisubstituted terpenoid oxiranes (rac-1a-rac-3a) was accomplished by employing the epoxide hydrolase activity Rhodococcus and Streptomyces spp. Depending on the biocatalyst, the biohydrolysis proceeded in an enantio-convergent fashion and gave the corresponding vic-diols in up to 97% ee at conversions beyond the 50%-threshold. In order to avoid a depletion of the ee of product by further oxidative metabolism, bioconversions had to be conducted in an inert atmosphere with exclusion of molecular oxygen. The synthetic applicability of this method was demonstrated by the asymmetric total synthesis of the monoterpenoid coumarin (R)-(+)-Marmin in 95% ee.     

A concise synthesis of asymmetrical N,N′-disubstituted guanidines

We present a new and concise method for the preparation of asymmetrical N,N′-disubstituted guanidines starting from thiourea via the reaction of N-Boc-protected N′-alkyl/aryl substituted thioureas with an amine in the presence of mercury(II) chloride and triethylamine.     

Facile synthesis of acyclic azanucleosides from N-pivaloyloxymethyl amides and sulfonamides: synthesis of aza-analogues of Ganciclovir

N-Pivaloyloxymethyl amides and sulfonamides, readily available from N-alkylation of both amides and sulfonamides with commercial chloromethyl pivaloate, were converted into acyclic azanucleosides via a one-pot base silylation/nucleoside coupling procedure.     

Catalytic photocarboxylation of 1,1-diphenylethylene with N,N,N′,N′-tetramethylbenzidine and carbon dioxide

Photocarboxylation of 1,1-diphenylethylene with N,N,N′,N′-tetramethylbenzidine (TMB) in MeCN under bubbling of CO₂ proceeded with high catalytic efficiency, giving 3,3-diphenylacrylic acid (DPA) and 3-hydroxy-3,3-diphenylpropionic acid (20). The turnover number (TON=(DPA+20)/TMB) reached 17. Similarly, 1-phenyl-1-cyclohexene yielded cis-2-acetamido-2-phenylcyclohexanecarboxylic acid with TON 5.9. As compared with related N,N-dimethylaniline derivatives, TMB is more resistant to photodecomposition, has the much larger absorbance in the S₀→S₁ transition, and has the lower quenching efficiency by CO₂. Probably these factors are partly responsible for the high TON observed for TMB.     

N,N′-Diisopropyl- and N,N′-dicyclohexylthiourea cadmium(II) complexes as precursors for the synthesis of CdS nanoparticles

Crystals of the cadmium(II) complexes of N,N-diisopropylthiourea and N,N-dicyclohexylthiourea were obtained and their X-ray single crystal structures determined. These complexes are air-stable, easy to prepare and inexpensive and decompose cleanly to give good quality crystalline CdS. The nanoparticles of CdS thus obtained showed quantum confinement effects in their optical spectra, with close to band-edge emission in luminescence experiments. The broad diffraction patterns observed are typical of nanodimensional particles. The variation of concentration of precursor-to-HDA ratio change the isolated materials from spheres to rod-shaped. TEM images showed agglomerates of needle-like plate of particles.     

Efficient iodine catalyzed chemoselective synthesis of aminals—an access to N,N-acetals by the addition of lactams to N-acyl imines

A highly efficient protocol has been developed for the synthesis of aminals from γ-butyrolactam and benzaldehyde using iodine as Lewis acid catalyst. The attack of γ-butyrolactam nucleophile to intermediate N-acyliminium ion was more favorable, when aryl aldehyde bears the electron donating group (EDG). Iodine plays a key role in these reaction transformations. This current mild protocol is environmentally benign and cost-effective method for the synthesis of industrially and pharmaceutically useful scaffolds.     

Convenient synthesis of fused pyrano[3,2-h]- and furo[3,2-h]benzo[f]coumarins from naphthalene-2,3-diol

The treatment of 8-propargyloxy-benzo[f]coumarin with boron trifluoride diethyl etherate in N,N-dimethylformamide under reflux or MW irradiation resulted in pyrano[3,2-h]benzo[f]coumarin, while the furo[3,2-h]benzo[f]coumarin is received from the treatment with N-methylformamide under MW irradiation.