Isonitrile Groups Research Articles

Isonitrile-Derivatized Indole as an Infrared Probe for Hydrogen-Bonding Environments

The isonitrile (NC) group has been shown to be a promising infrared probe for studying the structure and dynamics of biomolecules. However, there have been no systematic studies performed on the NC group as an infrared probe, when it is bonded to an indole ring. Here, we systematically study the NC stretching mode of two model compounds, 5-isocyano-1H-indole (5ICI) and 5-isocyano-1-methyl-1H-indole (NM5ICI), using Fourier transform infrared (FTIR) spectroscopy. The NC stretching frequency is shown to be strongly dependent on the polarizability of protic solvents and the density of hydrogen-bond donor groups in the solvent when NC is bonded to an indole ring. Infrared pump–probe studies of 5ICI in DMSO and in EtOH further support that the NC stretching mode could be used as a site-specific infrared probe for local environments when NC is bonded to an indole ring.

Second-generation aryl isonitrile compounds targeting multidrug-resistant Staphylococcus aureus.

Antibiotic resistance remains a major global public health threat that requires sustained discovery of novel antibacterial agents with unexploited scaffolds. Structure-activity relationship of the first-generation aryl isonitrile compounds we synthesized led to an initial lead molecule that informed the synthesis of a second-generation of aryl isonitriles. From this new series of 20 compounds, three analogues inhibited growth of methicillin-resistant Staphylococcus aureus (MRSA) (from 1 to 4 µM) and were safe to human keratinocytes. Compound 19, with an additional isonitrile group exhibited improved activity against MRSA compared to the first-generation lead compound. This compound emerged as a candidate worthy of further investigation and further reinforced the importance of the isonitrile functionality in the compounds' anti-MRSA activity. In a murine skin wound model, 19 significantly reduced the burden of MRSA, similar to the antibiotic fusidic acid. In summary, 19 was identified as a new lead aryl isonitrile compound effective against MRSA.

Novel 99mTc-Labeled Glucose Derivative for Single Photon Emission Computed Tomography: A Promising Tumor Imaging Agent.

In this study, a d-glucosamine derivative with an isonitrile group (CN5DG) was synthesized and it was chosen to coordinate with 99mTc for preparing 99mTc-CN5DG. 99mTc-CN5DG could be readily obtained with high radiochemical purity (>95%) and had great in vitro stability and metabolic stability in urine. The radiotracer demonstrated a positive response to the administration of glucose and insulin in S180 and A549 tumor cells in vitro, suggesting the mechanism of 99mTc-CN5DG into tumor cells was related to glucose transporters. Biodistribution studies in mice bearing A549 xenografts showed 99mTc-CN5DG had a high tumor uptake and high tumor-to-background ratios. SPECT/CT images further supported its ability for tumor imaging. As a cheap, conveniently made and widely available probe, 99mTc-CN5DG would become a potential "working horse" and be a breakthrough in 99mTc-labeled radiopharmaceuticals for tumor detection.

Cyanamide as an Infrared Reporter: Comparison of Vibrational Properties between Nitriles Bonded to N and C Atoms.

Infrared (IR) probes based on terminally blocked β-cyanamidoalanine (AlaNHCN) 1 and p-cyanamidophenylalanine (PheNHCN) 2 were synthesized, and the vibrational properties of their CN stretch modes were studied using Fourier transform infrared (FTIR) and femtosecond IR pump-probe spectroscopies in combination with quantum chemical calculations. From FTIR studies, it is found that the transition dipole strengths of the cyanamide (NHCN) group in 1 and 2 are much larger than those of the nitrile (CN) group but comparable to those of the isonitrile (NC) and azido (N3) groups in their previously studied analogs. The CN stretch frequencies in 1 and 2 are red-shifted from those in their nitrile analogs but more blue-shifted from the NC and N3 stretch frequencies in their isonitrile and azido analogs. The much larger transition dipole strength and the red-shifted frequency of the cyanamide relative to nitrile group originates from the n → π* interaction between the N atom's nonbonding (n) and CN group's antibonding (π*) orbitals of the NHCN group. Unlike aliphatic cyanamide 1, aromatic cyanamide 2 shows a complicated line shape of the CN stretch spectra. Such a complicated line shape arises from the Fermi resonance between the CN stretch mode of the NHCN group and one of the overtones of the phenyl ring vibrations and can be substantially simplified by deuteration of the NHCN into NDCN group. From IR pump-probe experiments, the vibrational lifetimes of the CN stretch mode in 1 were determined to be 0.58 ± 0.04 ps in D2O and 0.89 ± 0.09 ps in H2O and those in 2 were determined to be 1.64 ± 0.13 ps in CH3OD/dimethyl sulfoxide and 0.30 ± 0.05 and 2.62 ± 0.26 ps in CH3OH. The short time component (0.30 ± 0.05 ps) observed for 2 in CH3OH is attributed to the vibrational relaxation through Fermi resonance. These vibrational lifetimes are close to those of the nitrile and azido groups but shorter than those of the isonitrile group. Consequently, cyanamide behaves like an apparent vibrational hybrid of nitrile and isonitrile in that cyanamide is similar to nitrile in vibrational frequency and lifetime but to isonitrile in transition dipole strength. It is believed that cyanamide has the potential to be a strongly absorbing IR reporter of the conformational and environmental structure and dynamics of biomolecules in comparison to nitrile, a weak absorber.

Nitrile versus isonitrile adsorption at interstellar grain surfaces

Context. Almost 20% of the ~200 different species detected in the interstellar and circumstellar media present a carbon atom linked to nitrogen by a triple bond. Of these 37 molecules, 30 are nitrile R-CN compounds, the remaining 7 belonging to the isonitrile R-NC family. How these species behave in their interactions with the grain surfaces is still an open question. Aims. In a previous work, we have investigated whether the difference between nitrile and isonitrile functional groups may induce differences in the adsorption energies of the related isomers at the surfaces of interstellar grains of various nature and morphologies. This study is a follow up of this work, where we focus on the adsorption on carbonaceous aromatic surfaces. Methods. The question is addressed by means of a concerted experimental and theoretical approach of the adsorption energies of CH3CN and CH3NC on the surface of graphite (with and without surface defects). The experimental determination of the molecule and surface interaction energies is carried out using temperature-programmed desorption in an ultra-high vacuum between 70 and 160 K. Theoretically, the question is addressed using first-principle periodic density functional theory to represent the organised solid support. Results. The adsorption energy of each compound is found to be very sensitive to the structural defects of the aromatic carbonaceous surface: these defects, expected to be present in a large numbers and great diversity on a realistic surface, significantly increase the average adsorption energies to more than 50% as compared to adsorption on perfect graphene planes. The most stable isomer (CH3CN) interacts more efficiently with the carbonaceous solid support than the higher energy isomer (CH3NC), however.

Nitrile versus isonitrile adsorption at interstellar grains surfaces

Context. Almost 20% of the ~200 different species detected in the interstellar and circumstellar media present a carbon atom linked to nitrogen by a triple bond. Among these 37 molecules, 30 are nitrile R-CN compounds, the remaining seven belonging to the isonitrile R-NC family. How these species behave in presence of the grain surfaces is still an open question. Aims. In this contribution we investigate whether the difference between nitrile and isonitrile functional groups may induce differences in the adsorption energies of the related isomers at the surfaces of interstellar grains of different nature and morphologies. Methods. The question was addressed by means of a concerted experimental and theoretical study of the adsorption energies of CH3CN and CH3NC on the surface water ice and silica. The experimental determination of the molecule – surface interaction energies was carried out using temperature programmed desorption (TPD) under an ultra-high vacuum (UHV) between 70 and 160 K. Theoretically, the question was addressed using first principle periodic density functional theory (DFT) to represent the organized solid support. Results. The most stable isomer (CH3CN) interacts more efficiently with the solid support than the higher energy isomer (CH3NC) for water ice and silica. Comparing with the HCN and HNC pair of isomers, the simulations show an opposite behaviour, in which isonitrile HNC are more strongly adsorbed than nitrile HCN provided that hydrogen bonds are compatible with the nature of the model surface. Conclusions. The present study confirms that the strength of the molecule surface interaction between isomers is not related to their intrinsic stability but instead to their respective ability to generate different types of hydrogen bonds. Coupling TPD to first principle simulations is a powerful method for investigating the possible role of interstellar surfaces in the release of organic species from grains, depending on the environment.

Isonitrile as an Ultrasensitive Infrared Reporter of Hydrogen-Bonding Structure and Dynamics.

Infrared (IR) probes based on terminally blocked β-isocyanoalanine (AlaNC) and p-isocyanophenylalanine (PheNC) amino acids were synthesized. These isonitrile (NC)-derivatized compounds were extensively characterized by FTIR and femtosecond IR pump-probe spectroscopies, and a direct comparison was made with popularly used nitrile (CN)- and azide (N3)-derivatized analogs. It is shown that the isonitrile stretch frequency exhibits extremely high sensitivity to hydrogen-bonding interactions. In addition, the IR intensity of the isonitrile group is much higher than that of the nitrile group and almost as intense as that of the azido group. Furthermore, its vibrational lifetime is much longer than that of the nitrile and azido groups. To elucidate the origin of such a high H-bond sensitivity and IR intensity observed for isonitrile, extensive quantum chemical calculations were performed. It is shown that the Coulombic contributions to the vibrational frequency shifts of the isonitrile and nitrile stretch modes have opposite signs but similar magnitudes, whereas the contributions of exchange repulsion and charge delocalization to their frequency shifts are comparable. Therefore, the isonitrile stretch frequency is much more sensitive to H-bonding interactions because the blue-shifting exchange-repulsion effects are additionally enforced by such electrostatic effects. It is also shown that the much higher IR intensity of the isonitrile group compared to that of the nitrile group is due to the configuration reversal of the atomic electronegativity between the NC and CN groups. Owing to these features, we believe that isonitrile is a much better IR reporter of H-bonding structure and dynamics than the widely used nitrile and azide.

Discovery of new hazimycin congeners from Kitasatospora sp. P07101

In an analytical study of microbial broths, the actinomycete strain Kitasatospora sp. P07101 was found to produce three new congeners, which were designated hazimycins B (1), C (2), and D (3), together with the previously reported hazimycin (renamed hazimycin A (4)). The structures of these hazimycins were examined using various spectroscopic methods including nuclear magnetic resonance (NMR), and the results revealed that 1–3 were analogues of hazimycin with the replacement of one of the two isonitrile groups in 4 by an NH-formyl group in 1, the two isonitrile groups and an amide group by two NH-formyl groups and a nitrile group in 2, and the two isonitrile groups and two amide groups by two NH-formyl groups and two nitrile groups in 3. Only hazimycin A exhibited moderate antimicrobial activities against Gram-positive bacteria and Candida albicans. These results indicated that the presence of two isonitrile groups in the hazimycin structure is essential for antimicrobial activity.

Discovery and characterization of aryl isonitriles as a new class of compounds versus methicillin- and vancomycin-resistant Staphylococcus aureus

Methicillin- and vancomycin-resistant Staphylococcus aureus (MRSA and VRSA) have emerged as a global health concern. A new class of compounds featuring an aryl isonitrile moiety has been discovered that exhibits potent inhibitory activity against several clinically-relevant MRSA and VRSA isolates. Structure–activity relationship studies have been conducted to identify the aryl isonitrile group as the key functional group responsible for the observed antibacterial activity. The most potent antibacterial aryl isonitrile analogs (MIC 2 μM) did not show any toxicity against mammalian cells up to a concentration of 64 μM.

Vibronic spectroscopy of a nitrile/isonitrile isoelectronic pair: para-diisocyanobenzene and para-isocyanobenzonitrile.

The ultraviolet spectroscopy of isoelectronic pair para-diisocyanobenzene (pDIB) and para-isocyanobenzonitrile (pIBN) has been studied under gas-phase, jet-cooled conditions. These molecules complete a sequence of mono and disubstituted nitrile/isonitrile benzene derivatives, enabling a comparison of the electronic effects of such substitution. Utilizing laser-induced fluorescence (LIF) and resonant two-photon ionization (R2PI) spectroscopy, the S0-S1 electronic origins of pDIB and pIBN have been identified at 35,566 and 35,443 cm(-1), respectively. In pDIB, the S0-S1 origin is very weak, with b(3g) fundamentals induced by vibronic coupling to the S2 state dominating the spectrum at 501 cm(-1) (ν17, isocyano bend) and 650 cm(-1) (ν16, ring distortion). The spectrum extends over 5000 cm(-1), remaining sharp and relatively uncongested over much of this range. Dispersed fluorescence (DFL) spectra confirm the dominating role played by vibronic coupling and identify Franck-Condon active ring modes built off the vibronically-induced bands. In pDIB, the S2 state has been tentatively observed at about 6100 cm(-1) above the S0-S1 origin. In pIBN, the S0-S1 origin is considerably stronger, but vibronic coupling still plays an important role, involving fundamentals of b2 symmetry. The bending mode of the nitrile group dominates the vibronically-induced activity. Calculations carried out at the TD-DFT B3LYP/6-31+G(d) level of theory account for the extremely weak S0-S1 oscillator strength of pDIB and the larger intensity of the S0-S1 origins of pIBN and pDCB (para-dicyanobenzene) as nitrile groups are substituted for isonitrile groups. In pDIB, a nearly perfect cancellation of transition dipoles occurs due to two one-electron transitions that contribute nearly equally to the S0-S1 transition. The spectra of both molecules show no clear evidence of charge-transfer interactions that play such an important role in some cyanobenzene derivatives.

Antiplasmodial activity: The first proof of inhibition of heme crystallization by marine isonitriles

Over a decade ago Wright et al., proposed a putative antiplasmodial mechanism of action for marine isonitriles (1, and 3–6) and isothiocyanate (2) that involved interference in heme detoxification by Plasmodium falciparum thus inhibiting the growth of the parasite. In the current paper we describe the successful down scaling of Egan's β-hematin inhibition assay for analyses of small quantities of marine natural products as potential β-hematin inhibitors. The modified assay revealed for the first time that the most active antiplasmodial marine isonitrile 4 (IC50 13 nM) totally inhibited β-hematin crystallization while 5 (IC50 31 nM) and 6 (IC50 81 nM) showed inhibition at lower levels. A cursory ab initio molecular dynamics investigation into the relative stabilities of bonded complexes between isocyanate, isothiocyanate and isonitrile groups with the iron center of heme supported our findings that these marine metabolites do indeed interfere with biocrystallization of heme.

Adducts of nitrogenous ligands with rhodium(II) tetracarboxylates and tetraformamidinate: NMR spectroscopy and density functional theory calculations

Complexation of tetrakis(μ2-N,N'-diphenylformamidinato-N,N')-di-rhodium(II) with ligands containing nitrile, isonitrile, amine, hydroxyl, sulfhydryl, isocyanate, and isothiocyanate functional groups has been studied in liquid and solid phases using (1)H, (13)C and (15)N NMR, (13)C and (15)N cross polarisation-magic angle spinning NMR, and absorption spectroscopy in the visible range. The complexation was monitored using various NMR physicochemical parameters, such as chemical shifts, longitudinal relaxation times T1 , and NOE enhancements. Rhodium(II) tetraformamidinate selectively bonded only unbranched amine (propan-1-amine), pentanenitrile, and (1-isocyanoethyl)benzene. No complexation occurred in the case of ligands having hydroxyl, sulfhydryl, isocyanate, and isothiocyanate functional groups, and more expanded amine molecules such as butan-2-amine and 1-azabicyclo[2.2.2]octane. Such features were opposite to those observed in rhodium(II) tetracarboxylates, forming adducts with all kind of ligands. Special attention was focused on the analysis of Δδ parameters, defined as a chemical shift difference between signal in adduct and corresponding signal in free ligand. In the case of (1)H NMR, Δδ values were either negative in adducts of rhodium(II) tetraformamidinate or positive in adducts of rhodium(II) tetracarboxylates. Experimental findings were supported by density functional theory molecular modelling and gauge independent atomic orbitals chemical shift calculations. The calculation of chemical shifts combined with scaling procedure allowed to reproduce qualitatively Δδ parameters.

Metabolic Glycan Imaging by Isonitrile–Tetrazine Click Chemistry

Seeing the sugar coating: N-Acetyl-glucosamine and mannosamine derivatives tagged with an isonitrile group are metabolically incorporated into cell-surface glycans and can be detected with a fluorescent tetrazine. This bioorthogonal isonitrile-tetrazine ligation is also orthogonal to the commonly used azide-cyclooctyne ligation, and so will allow simultaneous detection of the incorporation of two different sugars.

Dual-sugar imaging using isonitrile and azido-based click chemistries

We report the first account of metabolically labelling N-acetylglucosamine, in conjunction with either N-acetylgalactosamine or N-acetylmannosamine using a combination of isonitrile- and azide-based chemistries. With the appropriately labelled fluorescent probe molecules, that react with either the azido or isonitrile groups, the method enabled co-visualisation of cancer cell glycoproteins.

Nonisomorphous X-Ray Structures of Tritylnitrile and Tritylisonitrile

The crystal structures of a related series of isosteric compounds, namely tritylnitrile 1, tritylisonitrile 2, and a solid solution of tritylnitrile/tritylisonitrile 3 have been determined by single crystal X-ray diffraction. The bond lengths, angles, and intermolecular interactions do not deviate significantly from previously reported nitriles and isonitriles. These isosteric compounds pack in nonisomorphous but very similar structures. Subtle differences between the packing of 1 and 2 are detailed. The solid solution of tritylnitrile/tritylisonitrile 3 is isomorphous with the structure of tritylnitrile 1. This solid solution possesses substitutional disorder involving the nitrile and isonitrile groups (Z′ = 2, nitrile/isonitrile occupancy ratios 53.7/46.3 and 54.6/45.4). The structure of tritylisonitrile 2 possesses positional disorder over two sites (Z′ = 2, occupancy ratio of 93.1/6.9). A comparison with previously reported nearly isosteric structures reveals that other chemically dissimilar compounds crystallize in each of the two molecular packing arrangements described in this report. Structure 1: monoclinic, P21/c, a = 18.049(11) A, b = 9.583(6) A, c = 17.824(11) A, β = 108.680(10)°, V = 2921(3) A3, Z = 8, R 1 = 0.0467, wR 2 = 0.1491. Structure 2: triclinic, P $$ \overline{1} $$ , a = 9.5877(13) A, b = 10.7479(14) A, c = 14.809(2) A, α = 88.457(2)°, β = 80.303(2)°, γ = 77.128(2)°, V = 1466.4(3) A3, Z = 4, R 1 = 0.0423, wR 2 = 0.1151. Structure 3: monoclinic, P21/c, a = 18.03464(15) A, b = 9.5739(8) A, c = 17.8251(11) A, β = 108.5920(10)°, V = 2917.4(4) A3, Z = 8, R 1 = 0.0587, wR 2 = 0.1734. The crystal structures of the isosteric pair tritylnitrile 1 and tritylisonitrile 2 are nonisomorphous while the structure of a solid solution of tritylnitrile/tritylisonitrile 3 is isomorphous with the structure of tritylnitrile 1.

Are Unsaturated Isocyanides so Different from the Corresponding Nitriles?

Simple unsaturated and cyclopropylic isocyanides are synthesized by an efficient and simple approach. These compounds with gradually increasing distance between the unsaturated moiety and the isonitrile group are studied by UV photoelectron spectroscopy and quantum chemical calculations, and also compared to the corresponding nitriles. The first photoelectron band of the unsaturated compounds is linked to removal of an electron from the HOMO, which corresponds to CC multiple-bond ionization in antibonding interaction with the π-isocyanide bond (in the same plane) for conjugated systems, or in antibonding interaction with the pseudo-π-CH(2) group for isolated systems. For the 1-ethenyl derivatives, both cyano and isocyano groups act as a π-electron acceptor from the vinyl group, but the isocyano π system is much more strongly destabilized (ionization energies (IEs) shift to smaller values) by vinyl (3.12 eV) than the cyano π system is (2.70 eV). In comparison with the 1-ethynyl derivatives, a less pronounced destabilization (2.69 eV) of π(NC) by the ethynyl system (1.86 eV for π(CN)), and nearly the same order of magnitude of the energetic gap between the total antibonding (π(CC)-π(NC)) and the total bonding (π(CC)+π(NC)) IEs for ethenyl and ethynyl compounds are noted. The huge values of these last-named data for H(2)C=CH-NC (3.85 eV) and for HC≡C-NC (4.04 eV) reflect the strong interaction between the unsaturated carbon-carbon moiety and the isocyanide group, and thus more efficient conjugation than for the corresponding nitriles.

Trifunctional99mTc based radiopharmaceuticals: metal-mediated conjugation of a peptide with a nucleus targeting intercalator

The development of molecular imaging agents with multiple functions has become a major trend in radiopharmaceutical chemistry. We present herein the syntheses of trifunctional compounds, combining an acridine orange (AO) based intercalator with a GRP receptor specific bombesin like peptide (BBN). Metal-mediated conjugation of these two functions via the [2 + 1] approach to the third function, the [M(CO)(3)](+) (M = (99m)Tc, Re) moiety, yielded the final trifunctional molecules. The strongly fluorescent acridine orange, a nuclear targeting agent, has been derivatised with 4-imidazolecarboxylate as a bidentate ligand and bombesin with an isonitrile group as a monodentate ligand. For cell and nuclear uptake studies, [Re(L(1)-BBN)(L(2)-Ical)(CO)(3)] type complexes were synthesized and characterized. For radiopharmaceutical purposes, the (99m)Tc analogues have been prepared in a stepwise synthesis. Fluorescence microscopy studies on PC-3 cells, bearing the BBN receptor, showed high and rapid uptake into the cytoplasm. For the bifunctional molecule, lacking the BBN peptide, no internalization was observed.

Marine sponge Hymeniacidon sp. amphilectane metabolites potently inhibit rat brain microglia thromboxane B2 generation

Neuroinflammation appears to involve release of thromboxane B2 (TXB2) and superoxide anion (O2−) by brain microglia (BMG). The purpose of this investigation was to determine the effect of five Hymeniacidon sp. amphilectane metabolites (HsH2.6, HsH1.11, HsH2.13, HsH2.29_456, and HsH2.11.X7.3) and two semi‐synthetic analogs (HsH1.11x and HsH1.11X2) on TXB2 and O2− generation from E. coli LPS‐activated rat BMG. Short and long term cell viability was assessed by lactate dehydrogenase (LDH) release (1.5 h) and mitochondrial dehydrogenase (MTH) activity (2.5–18 h), respectively. O2− levels were determined via superoxide dismutase‐inhibitable reduction of ferricytochrome C and TXB2 by EIA. Results were the following (n=3–4): all Hymeniacidon sp. metabolites and analogs potently inhibited TXB2 (IC50=0.20–5.69 μM) with low LDH release and minimal MTH inhibition. Comparison of IC50 of closely related amphilectane diterpenes HsH2.13 (IC50~0.20 μM) and HsH1.11 (IC50~0.23 μM) supports the observation that bioactivity is associated with presence of two isonitrile groups. However, the amphilectane diterpenoid skeleton plays a significant role, as suggested by comparison between IC50 of these two compounds and HsH1.11X2 (IC50~3.14 μM), where original isonitriles have been replaced by formamide groups. Lack of O2− inhibition would appear to suggest that all Hymeniacidon sp. metabolites and derivatives inhibit TXB2 synthesis by a cyclooxygenase‐dependent mechanism. Supported by Midwestern University and the RISE and SCORE Programs, University of Puerto Rico at the Río Piedras Campus.

Role of Nitrogen in the Formation of HC−N Films by CH4/N2 Barrier Discharge Plasma: Aliphatic Tendency

We have studied the influence of nitrogen on the chemical properties of the hydrogenated carbon nitride (a-CN(x):H) film deposited by CH(4)/N(2) dielectric barrier discharge (DBD) plasma. X-ray photoelectron spectroscopy (XPS) indicates that carbon and nitrogen form an unpolarized covalent bond in these C-N(x) materials, and the observed chemical shift in the C 1s and N 1s binding energy is explained with respect to N 1s incorporation. Furthermore, the average nitrogen content (N/C approximately 0.76) in the films was systematically varied by changing the nitrogen partial pressure (CH(4)/N(2) approximately from 5:1 to 1:7) which is well supported by the elemental analysis. Fourier transform infrared (FTIR) absorption spectra exhibit significant changes in different C-N, C identical withN, and NH/OH molecular bands at higher nitrogen concentration in the film. The isonitrile and nitrile groups (-NC and -CN) are increased with the increase of deposition time. In addition, the elemental analysis, proton NMR, and thermolysis mass spectrum show that the composition of the film with the ratio CH(4)/N(2) approximately 1:1 is C, 67.68; H, 9.88; N, 16.53 (in wt %) and that the film is composed of polymers, probably containing linear chains which are cleaved off on heating in vacuum.

Stereoselective synthesis of 10,14-dimethyloctadec-1-ene, 5,9-dimethyloctadecane, and 5,9-dimethylheptadecane, the sex pheromones of female apple leafminer

The stereoselective synthesis of (10 R,14 R)-10,14-dimethyloctadec-1-ene ( 1), (5 R,9 R)-5,9-dimethyloctadecane ( 2), and (5 R,9 R)-5,9-dimethylheptadecane ( 3) the sex pheromone components of female apple leafminer was accomplished by reductive elimination tosyl and isonitrile groups of dialkylated tosylmethyl isonitrile. The key steps involved were dialkylation of TosMIC with 1-iodo 2-methyl alkanes, which were derived from Evan's alkylation of chiral auxiliary and subsequent reduction.