An expedient synthesis of ellipticine via Suzuki-Miyaura coupling

A simple and efficient total synthesis of ellipticine was developed via the Suzuki-Miyaura coupling of sterically sensitive 2-hydroxybenzeneboronic acid with a multifunctional aryl halide using Pd(OAc)₂ as a catalyst and Cu(OAc)₂·H₂O as an additive in DMSO/H₂O as a key step followed by double N-arylation and cyclization.     

An efficient modification of the Hofmann rearrangement: synthesis of methyl carbamates

A series of methyl carbamates was synthesized using NaOCl as an oxidant in the presence of KF/Al₂O₃/MeOH at reflux in excellent yields.     

An efficient synthesis of futalosine

Futalosine is a naturally occurring nucleoside comprised of an inosine core with a 3-carboxyphenyl methylene ketone functionality replacing the C-5′ hydroxyl. Recent studies have shown that it is a key intermediate in an alternative biosynthetic pathway that generates menaquinone in a variety of bacterial species. Here we report the first synthesis of futalosine in seven steps from inosine in an overall 17% yield. This work will enable further studies on menaquinone biosynthesis in pathogenic bacteria.     

An efficient synthesis of N-tert-butoxycarbonyl-O-cyclohexyl-L-tyrosine

A facile and efficient synthesis of N-tert-butoxycarbonyl-O-cyclohexyl-L-tyrosine [Boc-Tyr(Chx)-OH] is described. Boc-Tyr-OH was treated with NaH in dimethylformamide and then with 3-bromocyclohexene to give N-Boc-O-(cyclohex-2-enyl)-L-tyrosine [Boc-Tyr(Che)-OH] in 70% yield. Hydrogenation of Boc-Tyr(Che)-OH over PtO2 afforded Boc-Tyr(Chx)-OH in almost quantitative yield. The highest yield was achieved when a side product in the synthesis of Boc-Tyr-OH, Boc-Tyr(Boc)-OH, was not removed, because it was also converted to Boc-Tyr(Che)-OH without any additional manipulations. The new synthetic method described here is convenient for practical use, and would facilitate the widespread use of the Chx group for the hydroxy-protection of Tyr.     

An efficient synthesis of varenicline

Synthesis of varenicline the antismoking drug has been achieved in six steps with 10% overall yield. A Diels-Alder reaction, oxidative cleavage of an olefin and reductive amination remain as key steps in the synthesis     

An efficient synthesis of oosporein

Fungal metabolite oosporein was prepared in four steps and 24% overall yield starting from 2,5-dimethoxytoluene. It was demonstrated that treatment of phoenicin with pyrrolidine and copper(II) acetate led to oosporein, whereas similar treatment of the isomeric ‘isophoenicin’ produced a benzofuran diquinone. No chromatography was required during any step of the synthesis.     

An efficient synthesis of Ecopladib

An efficient synthesis of Ecopladib, an indole inhibitor of cytosolic phospholipase A₂α, is described. A new reaction involving indole C3 reductive alkylation using an acetal in the absence of water and a novel transformation of the C2 methyl to an aldehyde via dimethyl sulfoxide-mediated oxygen-transfer reaction are used in the present synthesis, which dramatically increased the synthetic efficiency.     

An efficient synthesis of sulfamides

Here we report an efficient synthesis of sulfamides. 3,5-Lutidine was found to be an optimal solvent and catalyst for the reaction. The method was developed during our efforts to synthesize a series of novel FKBP-12 inhibitors in which the known ketoamide linker was replaced with sulfamide.     

An efficient and general urazole synthesis

A general two-step scheme for the synthesis of N4 substituted urazoles (i.e., 1,2,4-triazolin-3,5-diones) is described. The first step involves the reaction of a primary amine with 2.5 equiv of phenyl chloroformate to produce diphenyl (N-substituted)imidodicarbonates. The second step involves the reaction of these compounds with hydrazine to produce N4 substituted urazoles. The mild reaction conditions permit synthesis of N4 oxygenated urazoles, not available via existing methodology. Bicyclic urazoles can be prepared through the subsequent reaction of these N4-protected urazoles with 2.5 equiv of NaH in DMF together with either 1,3-dibromopropane or 2-(tert-butyldimethylsilyloxy)-1,3-dibromopropane in the presence of NaI. The resultant bicyclic urazoles are observed to display varying degrees of pyrimidalization at N1 and N2, depending on substituents.     

An efficient and green protocol for the preparation of cycloalkanols: a practical synthesis of venlafaxine

The condensation of arylacetonitriles with cyclic ketones using aqueous NaOH or KOH under phase transfer catalysis gives almost quantitative yields of cycloalkanols. This protocol is utilized for a practical synthesis of the antidepression drug, venlafaxine 1.     

An efficient preparation of vinamidinium hexafluorophosphate salts

Substituted acetic acids or acetyl chlorides react with phosphorus oxychloride in DMF to yield the vinamidinium salts 3a-j in moderate to excellent recrystallized yields (28-90%). The cations are conveniently isolated as their hexafluorophosphate salts, which are easily handled nonhygroscopic solids. The nitro compound 3l is prepared in 91% yield by nitration of the parent vinamidinium 3k. The X-ray crystal structure is reported for the 2-phenyl isomer 3e and displays minimal overlap of the two pi-systems.     

An Efficient, one-pot synthesis of isomeric ellipticine derivatives through intramolecular imino-Diels-Alder reaction

New analogues of isomeric ellipticine derivatives fused with biologically important pyrroloindole or chromene moiety have been synthesized by utilizing an intramolecular imino Diels-Alder reaction in a single step.     

An efficient and general synthesis of pyrroles

We have discovered that a wide range of 3-alkynyl-hydroxyalkanamine derivatives undergo 5-endo-dig cyclisations when exposed to silver nitrate supported on silica gel. Subsequent in situ dehydration of the resulting and sometimes isolable hydroxy-dihydropyrroles leads to pyrroles in essentially quantitative yields using this recoverable and reusable heterogeneous catalyst.     

An efficient synthesis of pregaliellalactone and desoxygaliellalactone

A short and efficient total synthesis of rac-desoxygaliellalactone and (+)-desoxygaliellalactone, via the biosynthetic intermediate pregaliellalactone, is described. The synthesis was achieved in only three steps, for (+)-desoxygaliellalactone including an enantioselective alkyl propiolate addition to 4-pentenal, a palladium catalysed alkylative lactonisation and an intramolecular Diels–Alder cycloaddition.     

An efficient synthesis of 2-hydroxyphenylphosphonates

The high yield conversion of phenols into diethyl 2-hydroxyphenylphosphonates via base catalyzed rearrangement of diethyl phenyl phosphates has been achieved.