Synthesis of β3-amino acid and peptides from D-ribose

Synthesis of new β³-amino acid, peptides and conformational analysis are reported from d-ribose, using Wittig olefination and Aza-Michael addition.     

Synthesis of novel β2,2-amino acid from D-mannose and attempted synthesis of peptides from the amino acid

The study describes the synthesis of new α,α-disubstituted β-amino acid (β^2,2-Caa) and attempts the synthesis of peptides from it. The β^2,2-Caa was prepared from D-(+)-mannose, using crossed aldol and Cannizzaro reactions.     

Synthesis and molecular structure analysis of venlafaxine intermediate and its analog

1-(cyano-(4-methoxyphenyl) methyl cyclohexanol(2), C₂₄H₃₂N₂O₂, a Venlafaxine intermediate is found to crystallize in both monoclinic(2a) and orthorhombic(2b) crystal systems. The form2a crystallizes in the space groupC2/c with the cell parametersa = 23.506(3),b = 5.550(3),c = 23.192(3), and β = 115.116(2)^∘.2b crystallizes in space groupP2₁2₁2₁ with cell parametersa = 5.7850(6),b = 11.2680(6), andc = 20.6730(19). The intermolecular hydrogen bonding in the case of the monoclinic polymorph leads to the formation of dimer. The synthesis, characterization, and crystal structure studies of Venlafaxine analog 1-[2-1-(4-dimethylamino-phenyl)-ethylideneamino]-1-(4-methoxy-phenyl)-ethyl]-cyclohexanol(4) is reported.4 crystallizes inP―1 space group with cell parametersa = 10.801(7),b = 12.078(7),c = 9.928(5), α = 96.12(5)^∘, β = 110.49(5)^∘, and γ = 112.42(6)^∘.     

Liquid chromatography tandem mass spectrometry method for the quantification of clonidine with LLOQ of 10 pg/mL in human plasma

A sensitive high-performance liquid chromatography-positive ion electrospray tandem mass spectrometry method was developed and validated for the quantification of clonidine in human plasma. Following liquid-liquid extraction, the analytes were separated using an isocratic mobile phase on a reverse-phase column and analyzed by MS/MS in the multiple reaction monitoring mode using the respective [M + H](+) ions, m/z 230 to 44 for clonidine and m/z 254 to 44 for the internal standard. The assay exhibited a linear dynamic range of 10-2000 pg/mL for clonidine in human plasma. The lower limit of quantification was 10 pg/mL with a relative standard deviation of less than 6.8%. Acceptable precision and accuracy were obtained for concentrations over the standard curve range. A run time of 2.5 min for each sample made it possible to analyze more than 250 human plasma samples per day. The validated method was successfully used to analyze human plasma samples for application in pharmacokinetic studies. Copyright (c) 2008 John Wiley & Sons, Ltd.     

Stereoselective synthesis of basiliskamides A and B via Prins cyclisation

A stereoselective and convergent approach to basiliskamides A and B is achieved through our recently developed strategy for the construction of polyketide precursors via Prins cyclisation. The approach mainly relies upon reductive opening of 1-iodomethyl cyclic ethers, Mitsunobu inversion, Takai olefination and Stille coupling along with Prins cyclisation.     

Total synthesis of (+)-cassaine via transannular Diels-Alder reaction

A full account of the total synthesis of (+)-cassaine ( 1) using the transannular Diels-Alder (TADA) reaction as the pivotal construction is described. The strategy began from Evans' oxazolidine 8, the only chiral source used for the total stereochemical outcome of the target molecule. The key intermediate 3 was obtained from 8 in 10 steps in 40% overall yield. Following extensive optimization, the coupling of 3 on both ends with another densely functional partner 2 followed by TADA reaction on macrocycle 4 cleanly furnished the tricycle 5. The stereochemical outcome in 5 was expected via a least-energetic transition state T4. A stereoselective reduction, hydroboration, and methyl cuprate 1,4-addition along with a few other functional interconversions transformed 5 into the key intermediate 37. Final tethering of dimethylaminoethyloxycarbonyl along with epimerization at C8 and alcohol deprotection at C3 yielded the natural product 1.     

Ruthenium-catalyzed azide-alkyne cycloaddition: scope and mechanism

The catalytic activity of a series of ruthenium(II) complexes in azide-alkyne cycloadditions has been evaluated. The [Cp*RuCl] complexes, such as Cp*RuCl(PPh 3) 2, Cp*RuCl(COD), and Cp*RuCl(NBD), were among the most effective catalysts. In the presence of catalytic Cp*RuCl(PPh 3) 2 or Cp*RuCl(COD), primary and secondary azides react with a broad range of terminal alkynes containing a range of functionalities selectively producing 1,5-disubstituted 1,2,3-triazoles; tertiary azides were significantly less reactive. Both complexes also promote the cycloaddition reactions of organic azides with internal alkynes, providing access to fully-substituted 1,2,3-triazoles. The ruthenium-catalyzed azide-alkyne cycloaddition (RuAAC) appears to proceed via oxidative coupling of the azide and alkyne reactants to give a six-membered ruthenacycle intermediate, in which the first new carbon-nitrogen bond is formed between the more electronegative carbon of the alkyne and the terminal, electrophilic nitrogen of the azide. This step is followed by reductive elimination, which forms the triazole product. DFT calculations support this mechanistic proposal and indicate that the reductive elimination step is rate-determining.     

Copper(I) iodide–catalyzed amidation of phenylboronic acids/aryl bromides using 4-dimethylaminopyridine as ligand

An efficient one-pot synthesis of N-arylbenzamide is described via reaction of phenylboronic acid/aryl bromide with benzamide in the presence of CuI (5 mol%) as catalyst, 4-dimethylaminopyridine (20 mol%) as the ligand, and Cs₂CO₃ (2 mmol) as the base. This protocol was applied to synthesize a small library of N-arylbenzamide in high yields.     

Chemo-enzymatic synthesis and biological evaluation of photolabile nicotinic acid adenine dinuclotide phosphate (NAADP+)

A chemo-enzymatic synthesis of novel caged NAADP+ without the formation of multiple cage compounds has been achieved. The biological activity of the caged NAADP+ was demonstrated by its fast uncaging in intact sea-urchin eggs.