Current Organic Synthesis - Volume 13, Issue 1, 2016

The synthesis of high optical purity chiral compounds is of current importance in organic and organometallic areas of the chemistry with further boost. Chiral compounds are important because of wide use in many areas such as pharmacy and food industry, etc. Reagents, catalysts or chiral auxiliaries that can control the stereochemistry of the products are required for the synthesis of chiral compounds. Furthermore, the reagents used must be able to be recycled. In recent decades, Ephedra derivative compounds have been widely used as catalyst chiral ligands or chiral inductors in asymmetric synthesis. To our knowledge, no review about Ephedra derivative compounds as chiral auxiliaries used with organometallics in alkylation reactions to carbonyl compounds, has been published. In this paper, the use of N-substituted and N-disubstituted ephedra compounds as chiral auxiliary ligands in alkylation, alkenylation and alquinilation reactions of carbonyl and imine compounds is summarized.

Substantial attention has been given in developing novel heterocyclic compounds as these have been found to exhibit varied biological activities. Benzothiazoles belong to one of the special categories of heterocyclic compounds with a wide range of biological activities such as antimicrobial, antitumor, antidiabetic, antitubercular, antimalarial, anticonvulsant, anthelmintic, analgesic, antiinflammatory and many more. These compounds have been serving as leads for researchers who are actively involved in synthesizing and evaluating their biological activities. Such an extensive work has stimulated further development of new benzothiazole derivatives with enhanced biological activities. This review focuses on the various approaches on the synthesis of benzothiazole derivatives viz., conventional, green, combinatorial and microwave-assisted methods. It also highlights various biological activities of the currently synthesized benzothiazoles.

The tetracyclic indoloquinoline alkaloids, cryptolepine, neocryptolepine, isocryptolepine and their analogues, isolated from the West African shrub Cryptolepis sanguinolenta are known to display promising antimalarial, antibacterial, antiviral, antihyperglycemic and cytotoxic properties. Biogenesis of these different linear and angular indoloquinolines are most probably through the reaction of anthranilic acid with selected indole derivatives – indoxyl, oxindole, 3-formyl indole, etc., all by-products during tryptophan biosynthesis from chorismate. As part of our ongoing screening program of bioactive compounds, several of these natural products and their derivatives, including few halogenated metabolites were synthesized in our laboratory using simplified domino approaches. Apart from codifying their probable biosynthetic pathways, this article also summarizes our synthetic studies, most of which were planned mimicking the natural biosynthetic pathways.

Thietanes are important intermediates in organic synthesis. They have been widely applied in the preparation of sulfur-containing compounds via ring-opening and ring expansion. They produce thiols and thioether derivatives via ring opening reactions and yield five- to eight-membered, even larger, heterocyclic compounds via ring expansions. Ring opening and expansion reactions include electrophilic and nucleophilic, oxidative and reductive, transition metals and acid-catalyzed, insertion, and photoirradiated processes. The ring opening and expansion reactions generally show good regioselectivity. The electronic effect plays a crucial role in controlling the regioselectivity in the ring opening and expansion reactions of unsymmetric thietanes invloving electropositive intermediates. The regioselectivities in various ring opening reactions and expansions of unsymmetric thietanes are summarized and discussed herein. Mechanisms on some of the important ring opening and expansion reactions of thietanes are introduced as well.

Research on the synthesis of α-D-glucose pentaacetate 2 was investigated. In particular, various methods utilized for the synthesis of compound 2 were described in detail. Among them, acid catalysts including protonic acid and Lewis acid have received most attention.

Six-electron oxidation of hexahydroxybenzene C6(OH)6 leads to cyclohexanehexaone (CO)6 via two intermediates, tetrahydroxy-1,4-benzoquinone and rhodizonic acid (5,6-dihydroxycyclohex-5-ene-1,2,3,4-tetraone). All these quinoid compounds show a rich and colorful chemistry: formation of chromophoric metal complexes is a special feature of the compounds, which have been employed as specific reagents for metal ions. The formation of colored complexes even with alkali and earth alkali metal ions – not only with transition-metal ions – is a peculiarity. The derivatization of hydroxyl and oxo-functions proceeds as expected, but is superimposed by complex tautomerism between ortho-quinoid and para-quinoid counterparts as well as formation of hydrates of the keto functionalities. The generation of aromatic anions is a special feature of the compounds, its many implications having rendered them favorite objects of study for theoretical and computational chemists. Dimerization, ring contraction and decarbonylation processes are another class of pathways which offer a wide field for mechanistic studies. The general chemistry of the compound series from hexahydroxybenzene to cyclohexanehexaone is reviewed, focusing on reactions, mechanisms and derivatizations along with some important structural and analytical features.

Various room temperature ionic liquids (RTILs), notably, 1-methoxyethyl-3-methylimidazolium trifluoroacetate [MeOEtMIM]+[CF3COO]¯ , have been used to promote the Knoevenagel condensation to afford substituted olefins. All reactions proceeded effectively in the absence of any other catalysts or co-solvents with good to excellent yields. This method is simple and applicable to reactions involving a wide range of aldehydes and ketones with methylene compounds. The ionic liquid can be recycled without noticeable reduction of its catalytic activity. A plausible reaction mechanism is proposed.

Surface modified activated carbon with methanesulfonic acid (AC-MsOH) is found to catalyze [3+2] cycloaddition reactions between alkyl/aryl azides and nitroolefins which yielded regioselective 1,5-disubstituted-1,2,3-triazolines in high yields under mild conditions.

The synthesis of 4-amino-4H-[1,2,4]triazino[5,6-b]indole-3-thiol 1 via the reaction of isatin with thiocarbohydrazide in glacial acetic acid is described in this study. New fused heterotetracyclic nitrogen systems, such as [1,2,4,5]tetrazino[6',1':3,4][1,2,4]-triazino[5,6-b]indoles 4 and 6; [1,2,4]triazino[3',2':3,4][1,2,4]triazino[5,6- b]indole 8; [1,3,4]thiadiazolo[2',3':3,4][1,2,4]triazino[5,6-b]indoles 9, 11 and 12; pyrazolo[5',1':3,4]-[1,2,4] triazino[5,6-b]indole 16; and [1,3,4]thiadiazino[2',3':3,4][1,2,4]triazino[5,6-b]indoles 18, 20 and 23, were achieved by treating 1 with guanidine, thiosemicarbazide, thioformic acid hydrazide, glycine and CS2, in ethanolic ethoxide, triethyl orthoformate, ethyl cyanoacetate, ethyl chloroformate and dichloroacetic acid, respectively. The structures of the products were deduced from their elemental analyses and spectral data (IR, 1H-NMR and13C-NMR). The antimicrobial activity of some of the synthesized compounds was also determined.

We present a straightforward route for the preparation of orthogonally protected oxadiazole-based building blocks in high yields. Their structures contain a Boc-protected amine and an ester group, thus rendering the compounds amenable to functionalization or integration into larger structures. Thus, we provided access to interesting and innovative building blocks/decorated scaffolds for drug discovery.

Conjugate addition of dialkyl phosphites and ethyl phenylphosphinate to electron-deficient alkenes containing ester, nitrile or amide group under PBu3 catalysis afforded corresponding phosphonates and phosphinates in high yields within short reaction times. Under the optimized conditions developed, the chemistry was free from side reactions involving competitive phosphine-catalyzed dimerization of the activated alkene. Long chain alkyl groups in the phosphite were well tolerated in this transformation. The catalytic activity of PBu3 was far superior to that of tertiary amines. High efficiency, mild reaction conditions, and ease of the catalyst recovery make the proposed procedure competitive with the classical base-promoted reaction.

Novel α-amino acids bearing 1,2,4-triazinone and steroidal moieties (N,C-disubstituted glycine) (5a and 5b) and the related systems (6 and 7) have been produced from condensation of 6-(8-aminophenyl)-4-phenyl-3-thioxo-1,2,4-triazin(2H)-5-one (1) with the selective steroids, 5-α-Androstan-17β-ol-3-one (2a) and Transandrosterone (2b) followed by addition of hydrocyanic acid and acidic hydrolysis. A nucleophilic substitution of mercapto group by 4-fluoro aniline and sulfanilamide of 5 afforded the corresponding α-amino acids 6 and 7. These newly synthesis compounds are further evaluated for enzymatic effects against some fungi (Cellobiase activity).

The deoxygenation of phosphine oxides was studied on two model reactions, on the reduction of 3- methyl-1-phenyl-3-phospholene 1-oxide and triphenylphosphine oxide using an aralkylsilane, arylsilanes, diarylsilanes, a disiloxane, a polysiloxane and a disilane under solvent-free, thermal or microwave-assisted conditions. The deoxygenations were optimized, and the reactivity of the silanes was evaluated. User-friendly accomplishments were elaborated.