•Monoalkynylpyridines were prepared via Sonogashira cross-coupling reaction.•Monoalkylpiperidines were prepared via mild hydrogenation of monoalkynylpyridines.•The reactions proceeded in moderate to excellent yields.Monoalkynylpyridines were prepared via a Sonogashira cross-coupling reaction between monoiodopyridines and alkynes. Mild hydrogenation of the obtained monoalkynylpyridines was then conducted to produce the corresponding monoalkylpiperidines in moderate to excellent yields. The hydrogenation reaction was carried out under H2 (1 atm) in the presence of 10 wt% Pd/C (5 eq) in either AcOH or MeOH at room temperature. The present mild method is therefore useful for the quick and easy preparation of monoalkylpiperidines.Download high-res image (126KB)Download full-size image

Elastin is a vital extracellular matrix protein, which is known for providing elasticity in numerous tissues. It is formed by the self-assembly and subsequent crosslinking of elastin precursor, tropoelastin. Two tetrafunctional, pyridinium-based amino acids desmosine and isodesmosine are exclusively found in elastin and play an important role as crosslinkers. Structural elucidation of elastin has eluded scientists to date, owing to the highly cross-linked structure and insoluble nature. Therefore, in this study, we aimed to synthesize a desmosine-containing cyclic peptide as a partial elastin mimic, in order to eventually facilitate the elucidation of the crosslinking pattern of elastin by mass spectrometric analysis.Download high-res image (122KB)Download full-size image

4-Methyl-5-pentylbenzene-1,3-diol (MPBD) is a secondary metabolite of SteelyA polyketide synthase, which controls cell aggregation and spore maturation of Dictyostelium discoideum. In this study, chemical synthesis of MPBD and its derivatives was achieved. Structure–activity relationship (SAR) studies for antimicrobial activities against Escherichia coli and Bacillus subtilis were also conducted.

•A new lanostane triterpene was extracted from Ganoderma lucidum.•Use of ionic liquid was attempted as the extraction solvent.•Structure of the isolated compound was elucidated by spectroscopic analysis.•The newly isolated lanostane natural product was named ganoderic acid Σ.A new lanostane triterpene was extracted from Ganoderma lucidum using cellulose-dissolving ionic liquids. The structure of the isolated compound was elucidated by spectroscopic analysis, including NMR, MS, and a modified Mosher’s method. The newly isolated lanostane natural product was named ganoderic acid Σ.

•This is the first synthetic study of sesquiterpene lactone cnicin.•The side chain of cnicin was synthesized via two routes.•A semi-synthesis of cnicin was achieved.Cnicin is a germacranolide sesquiterpene lactone that possesses potent inhibitory activity against the protozoan parasite Trypanosoma brucei, which causes human African trypanosomiasis (HAT). Although cnicin has an interesting structure and attractive biological activity, synthetic studies of cnicin have not yet been reported. This report describes the synthesis of the protected side chain carboxylic acid moiety at C8 of cnicin via two routes starting from l-ascorbic acid. In addition, esterification between the synthetic side chain and salonitenolide derivative, which can be achieved via hydrolysis of cnicin and protection of the primary alcohol, was conducted. Thus, a semi-synthesis of cnicin was achieved.

Isodesmosine and desmosine are crosslinking amino acids that are present only in elastin. They are useful biomarkers for the degradation of elastin, which occurs during the progression of chronic obstructive pulmonary disease (COPD) and related diseases. This Letter describes the synthesis of [13C3,15N1]-labeled isodesmosine, using Chichibabin pyridine synthesis as a key reaction. The labeled isodesmosine is a potential internal standard for the quantitative LC–MS/MS analysis of desmosines in elastin degradation.

Isolated from the Jamaican cyanobacterium Lyngbya majuscula, the jamaicamides are unique, mixed polyketide-peptides reported to be sodium channel blockers. The polyketide moiety contains an (E)-chloroolefin, an undetermined methyl stereocenter (C9), and an (E)-olefin (C10–C11). Herein we report the stereo- and regioselective synthesis of the polyketide moiety of the jamaicamides via a Julia–Kocienski coupling as the key step.

Cynaropicrin is a guaianolide sesquiterpene lactone, which has potent in vitro and in vivo inhibitory activity against Trypanosoma brucei, the protozoan parasite that causes human African trypanosomiasis (HAT; sleeping sickness). Herein, we describe the synthesis of cynaropicrin’s deuterated derivative, cynaropicrin-d4, by the replacement of the side chain of natural cynaropicrin. The synthesized cynaropicrin-d4 could be employed as an internal standard for liquid chromatography–mass spectrometry (LC–MS) analysis, in the pharmacokinetic study of cynaropicrin. This could potentially advance the study of this therapeutic lead.

Desmosine is a crosslinking pyridinium amino acid of elastin and is an attractive biomarker for the diagnosis of chronic obstructive pulmonary disease (COPD). Herein, we describe the total synthesis of natural desmosine and its deuterated derivatives. The synthesized deuterated derivatives could be used as internal standards for the development of an isotope-dilution liquid chromatography–mass spectrometry (LC–MS/MS) analytical method for the accurate determination of desmosine in clinical samples. The key features of our synthesis are stepwise chemo- and regioselective palladium-catalyzed Sonogashira and Negishi cross-coupling reactions for the efficient introduction of the amino acid side chains onto the pyridine core.

The tetrasubstituted pyridinium amino acids isodesmosine and desmosine are cross-linkers of elastin and are attractive biomarkers for the diagnosis of chronic obstructive pulmonary disease (COPD). In this study, the biomimetic total synthesis of isodesmosine and desmosine via a lanthanide-promoted Chichibabin pyridine synthesis using the corresponding aldehyde and amine hydrochloride is reported.

Desmosine-CH2, an analog of the elastic tissue degradation biomarker desmosine, can be regarded as a potential internal standard for precise quantification of desmosines by LC-MS/MS. In this study, the chemical synthesis of desmosine-CH2 was completed in 22% overall yield in five steps. The LC-MS/MS analysis of desmosine-CH2 was also achieved.

Cynaropicrin is a guaianolide sesquiterpene lactone with a 5-7-5 tricyclic skeleton, four exo-olefins, and two hydroxyl groups. Recently, it was found that the compound is a potent in vitro and in vivo inhibitor of the protozoan parasite Trypanosoma brucei, which causes human African trypanosomiasis (HAT; sleeping sickness). In this Letter, chemical derivatization of cynaropicrin and the structure–activity-relationship (SAR) study against T. brucei is described.

1,2,3,5-Tetrasubstituted pyridinium amino acid isodesmosine is a crosslinking amino acid of elastin and is an attractive biomarker for the diagnosis of chronic obstructive pulmonary disease (COPD). Herein, we report an application of the Chichibabin pyridine synthesis to the total synthesis of isodesmosine. Specifically, the appropriate protected lysine and the corresponding aldehyde were reacted using Pr(OTf)3 in H2O/MeOH.

A three-step synthesis of (R)-7-hydroxycarvone (1), which is anticipated to be a valuable building block for the versatile preparation of natural products, is described. Optimization of the reaction conditions for photooxygenation and migration of (S)-α-pinene 2, tetrapropylammonium perruthenate (TPAP) oxidation of the generated alcohol, and a subsequent ring-opening reaction in the presence of Cu(OTf)2 led to the synthesis of 1 with good reproducibility. The desired product 1 was thus obtained in 46% yield over three steps.

Desmosine, a crosslinking amino acid of elastin, is an attractive biomarker for diagnosis of chronic obstructive pulmonary disease (COPD). In this study, the first total synthesis of (+)-desmosine was achieved in 11% overall yield in 13 steps utilizing stepwise and regioselective Sonogashira cross-coupling reactions.

Desmosine, a crosslinking pyridinium amino acid of elastin, is an attractive biomarker for the diagnosis of chronic obstructive pulmonary disease (COPD). In this study, the total synthesis of (+)-desmosine is reported utilizing chemo- and regioselective Sonogashira and Negishi cross-coupling reactions in 15% yield over six steps.

Desmopyridine, isolated from the acid hydrolysates of bovine ligamentum nuchae, is an elastin crosslinker and an amino acid that has a 3,4,5-trisubstituted pyridine skeleton. Herein we report the first total synthesis of (+)-desmopyridine in 10% yield over six steps starting from 4-aminopyridine via chemo- and regioselective palladium-catalyzed Sonogashira and Negishi cross-coupling reactions.2-(S)-((tert-Butoxycarbonyl)amino)-3-hydroxypropionic acidC8H15NO5[α]D20=+1.2 (c 1.0, MeOH)Source of chirality: the precursorAbsolute configuration: (S)tert-Butyl 2-(S)-((tert-butoxycarbonyl)amino)-3-hydroxypropanoateC12H23NO5[α]D25=-20.8 (c 1.6, EtOH)Source of chirality: the precursorAbsolute configuration: (S)tert-Butyl 2-(S)-((tert-butoxycarbonyl)amino)-3-iodopropanoateC12H22INO4[α]D25=-11.5 (c 1.0, MeOH)Source of chirality: the precursorAbsolute configuration: (S)tert-Butyl 2-(S)-((tert-butoxycarbonyl)amino)-5-(trimethylsilyl)pent-4-ynoateC17H31NO4Si[α]D25=+54.0 (c 0.1, CHCl3)Source of chirality: the precursorAbsolute configuration: (S)tert-Butyl 2-(S)-((tert-butoxycarbonyl)amino)pent-4-ynoateC14H23NO4[α]D25=+44.7 (c 0.1, CHCl3)Source of chirality: the precursorAbsolute configuration: (S)(S)-tert-Butyl 2-(tert-butoxycarbonylamino)-5-(3,5-dibromopyridin-4-yl)pent-4-ynoateC19H24Br2N2O4[α]D20=+25.6 (c 0.1, CHCl3)Source of chirality: the precursorAbsolute configuration: (S)(2S,2′S)-Benzyl 4,4′-(4-((S)-5-(tert-butoxy)-4-(tert-butoxycarbonylamino)-5-oxopent-1-ynyl)pyridine-3,5-diyl)bis(2-(tert-butoxycarbonylamino)butanoate))C51H68N4O12[α]D20=+32.1 (c 0.1, CHCl3)Source of chirality: the precursorAbsolute configuration: (S), (S), (S)DesmopyridineC18H28N4O6[α]D20=+10.2 (c 0.1, H2O)Source of chirality: the precursorAbsolute configuration: (S), (S), (S)

Shikimic acid, the starting material in the commercial synthesis of oseltamivir phosphate (Tamiflu®), was efficiently extracted and isolated from Ginkgo biloba leaves utilizing the ionic liquid 1-butyl-3-methylimidazolium chloride ([bmim]Cl), which dissolves cellulose.

The jamaicamides, isolated from cyanobacterium Lyngbya majuscula in Jamaica, are unique mixed polyketide-peptides that are reported to be blockers of the sodium channels. The peptide moiety contains a pyrrolinone ring and a β-methoxy enone functionality. Herein, we report the stereoselective synthesis of the N-(Boc)2-protected peptide moiety of the jamaicamides by utilizing Meldrum’s acid starting from l-alanine and N-Boc-β-alanine.

ESR study of enediyne calicheamicin γ1I with phenyl tert-butyl nitrone (PBN) gave a significant kinetic isotope effect (kH/kD = 1.8) for the formation of the phenyl radical PBN monoadducts.

ESR study of enediyne calicheamicin γ1I with phenyl tert-butyl nitrone (PBN) gave a significant kinetic isotope effect (kH/kD = 1.8) for the formation of the phenyl radical PBN monoadducts.

Desmosine-CH2, an analog of the elastic tissue degradation biomarker desmosine, can be regarded as a potential internal standard for precise quantification of desmosines by LC-MS/MS. In this study, the chemical synthesis of desmosine-CH2 was completed in 22% overall yield in five steps. The LC-MS/MS analysis of desmosine-CH2 was also achieved.

Shikimic acid, the starting material in the commercial synthesis of oseltamivir phosphate (Tamiflu®), was efficiently extracted and isolated from Ginkgo biloba leaves utilizing the ionic liquid 1-butyl-3-methylimidazolium chloride ([bmim]Cl), which dissolves cellulose.

Desmosine, a crosslinking amino acid of elastin, is an attractive biomarker for diagnosis of chronic obstructive pulmonary disease (COPD). In this study, the first total synthesis of (+)-desmosine was achieved in 11% overall yield in 13 steps utilizing stepwise and regioselective Sonogashira cross-coupling reactions.