An efficient stereoselective synthesis of (2S,3S)-3-hydroxypipecolic acid using chlorosulfonyl isocyanate

An efficient stereoselective syntheses of (2S,3S)-3-hydroxypipecolic acid and (2R,3S)-2-hydroxymethylpiperidin-3-ol were achieved from p-anisaldehyde via the regioselective and diastereoselective introduction of an N-protected amine group using chlorosulfonyl isocyanate, ring-closing methathesis, and oxidation of p-methoxyphenyl group as the key steps.     

Total synthesis of (+)-valienamine and (−)-1-epi-valienamine via a highly diastereoselective allylic amination of cyclic polybenzyl ether using chlorosulfonyl isocyanate

The total synthesis of (+)-valienamine and (−)-1-epi-valienamine was concisely accomplished from readily available d-glucose via a highly diastereoselective amination of chiral benzylic ether using chlorosulfonyl isocyanate, intramolecular olefin metathesis, and diastereoselective reduction of cyclic enone using l-Selectride as the key steps.     

Chiron approach to formal synthesis of both antipodes of cis 3-hydroxypipecolic acid

The efficient and practical formal syntheses of both enantiomers of cis 3-hydroxypipecolic acid were accomplished from cis aziridine-2-carboxylate as the common synthetic precursor. The key steps involved are stereo and regioselective aziridine ring opening, reductive cyclization and selective N-debenzylation over O-debenzylation reactions.     

Novel synthetic method for allylic amination of cyclic allylic ethers using chlorosulfonyl isocyanate

The introduction of amines to allylic or benzylic position of cyclic compounds with chlorosulfonyl isocyanate is developed in high to excellent yields. This method provides a novel access to biologically active compounds including the framework of 1-aminoindanes, 1-aminotetralines, and 1-amino-2-hydroxy cyclic compounds. Mechanistic evidence for the reaction pathway is also provided.     

酶催化反式肉桂酸类似物的不对称氨化反应

在开展应用红酵母PAL酶合成L-苯丙氨酸的基础上,本文首次探讨了该酶不对称氨化反应对部分合成底物的选择性,以拓展它在重要的苯丙氨酸类似物合成方面的应用。     

A concise synthesis of (−)-cytoxazone and (−)-4-epi-cytoxazone using chlorosulfonyl isocyanate

A concise synthesis of (−)-cytoxazone and its stereoisomer (−)-4-epi-cytoxazone, novel cytokine modulators, has been accomplished each in six steps from readily available p-anisaldehyde with good diastereoselectivity. Key steps in the synthesis include the regioselective and diastereoselective amination of anti- and syn-1,2-dimethyl ethers with chlorosulfonyl isocyanate and the subsequent regioselective cyclization of the diol to construct the oxazolidin-2-one core. The diastereoselectivity of amination reaction using CSI was explained by the Cieplak electronic model via S_N1 mechanism and neighboring group effect, leading to the retention of the configuration.     

Synthesis of phosphinic and phosphoric analogs of aspartic acid

Approaches to the synthesis of 1-amino- and 2-amino-2-carboxyethylphosphinic and-phosphoric acids have been studied. A convenient method for the preparation of phosphinic acids is the reactions of ethyl diethoxymethylphosphonite with ethyl acetamidomethylenemalonate and ethyl 2-acetamidoacrylate.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 2066–2069, August, 1996.     

Nitration and amination of polyphenylene oxide: Synthesis, gas sorption and permeation analysis

A high degree of nitration of polyphenylene oxide (PPO) was successfully achieved by carefully optimizing synthetic protocol. The reduction of nitro group to amino could be done quantitatively. The physical properties of formed polymers were investigated and correlated with gas sorption and permeation properties. The formed polymers were amorphous in nature as revealed by wide angle X-ray diffraction spectra. An increase in the packing density in comparison to unsubstituted PPO as a result of induced polarity was indicated by lowering of fractional free volume and d-spacing. The substitution by either nitro or amino group increased the chain stiffness as revealed by the dynamic mechanical analysis. Though both, nitro and amino group substitution on PPO led to a decrease in pure gas permeability, the selectivity of various gas pairs was increased by these substitutions. The gas sorption analysis revealed that both, solubility selectivity and diffusivity selectivity were increased by these polar group substitutions. The nitro group substitution was more effective in improving solubility selectivity, while amino group substitution was more effective in improving diffusivity selectivity.     

Synthesis of 2,2-difluoro-3H-benzothiophen-3-ol via a difluorocarbene insertion reaction,investigating the scope for further derivatization

A simple, and efficient synthesis of 2,2-difluoro-3H-benzothiophen-3-ol using readily available sodium chlorodifluoroacetate (SCDA) is reported. We also explore new chemistry of these difluoro compounds. The salient feature of this approach includes operational simplicity and offers potential access to synthetically challenging building blocks for further elaboration. Functional group transformations of this new heterocycle are also presented.     

Synthesis of Fmoc-protected aza-β-amino acids via reductive amination of glyoxylic acid

The reductive amination of glyoxylic acid, with a protected Fmoc hydrazine, has been developed as a simple and efficient method for the preparation of Fmoc-aza-β³-amino acid residues (aza-β³-aa). Anchoring on resin of these residues will be described as well as the synthesis of hybrid peptide.     

Efficient syntheses of enantioenriched (R)-pipecolic acid and (R)-proline via electrophilic organocatalytic amination

Five-step syntheses of (R)-pipecolic acid and (R)-proline are described, respectively, from cyclohexene and cyclopentene. The key step involves the organocatalytic α-amination of functionalized aldehydes.     

Synthesis of alpha-hydrazino ketones via regio- and stereoselective electrophilic amination of manganese enolates and enamines

A straightforward procedure for the regio- and stereoselective synthesis of alpha-hydrazino ketones is described. Manganese enolates and manganese enamines derived from ketones and from the corresponding N-sulfinylimines react with azodicarboxylate esters (DTBAD and DEAD) in a regioselective fashion to afford in good to excellent yields the kinetic alpha-hydrazino ketones as sole or highly prevalent products. When enantiopure N-sulfinyl manganese enamines were used the stereoselectivity of these reactions ranged from 40% to 68% ee.     

Synthesis and conformational analysis of glycomimetic analogs of thiochitobiose

The synthesis of six analogs of N,N′-diacetylchitobiose is reported, including a novel transglycosylation reaction for the preparation of S-aryl thioglycosides. The conformations of the compounds were studied by a combination of NMR spectroscopy and molecular modeling, using force field calculations. In the case of the S-aryl thioglycosides with exclusively S-glycosidic linkages, dihedral angles of the disaccharidic S-glycosidic bonds, Φ′ and Ψ′ and of the S-arylglycoside bonds, Φ and Ψ, were found to be similar, whereas they were different in mixed glycosides and in a thiazoline derivative. An adequate correlation between the calculated H,H-distances of the local minima and the measured NOE contacts was achieved by applying population-weighted averages over participating conformers based on weighted relative energies.     

Scalable synthesis of (−)-trans-3-hydroxypipecolic acid via a useful chiral building block

A scalable synthesis of (−)-trans-2-(hydroxymethyl)-1,2,3,6-tetrahydropyridin-3-ol, a versatile chiral building block is described along with its transformation to (−)-trans-3-hydroxypipecolic acid.     

Efficient One-Pot Synthesis of 2,2-Dimethyl-2H-chromenes via Pd(II)-Catalyzed Coupling and SiO2-Promoted Condensation of o-Halophenols with 2-Methyl-3-buten-2-ol

An efficient synthesis of 2,2-dimethyl-2H-chromenes was accomplished by Pd(II)-catalyzed coupling and SiO₂-promoted condensation of o-halophenols with 2-methyl-3-buten-2-ol (1,1-dimethylallyl alcohol) in one pot. The method is very general and can be useful for the synthesis of some natural 2,2-dimethyl-2H-chromenes.     

Regioselective alkynylation of 2-aryl-4-chloro-3-iodoquinolines and subsequent arylation or amination of the 2-aryl-3-(alkynyl)-4-chloroquinolines

Palladium-CuI catalyzed Sonogashira coupling of 2-aryl-4-chloro-3-iodoquinolines with terminal acetylenes (1 equiv) in triethylamine afforded the 2-aryl-3-(alkynyl)-4-chloroquinolines as sole products. The 2-aryl-4-chloro-3-iodoquinolines coupled with excess terminal acetylenes (2.5 equiv) in dioxane/water to yield the 2-aryl-3,4-bis(alkynyl)quinoline derivatives in a one-pot operation. The 2-aryl-3-(alkynyl)-4-chloroquinolines were, in turn, subjected to arylation via Suzuki cross-coupling with arylboronic acid derivatives or amination with methylamine, respectively. The structures of the products of successive Sonogashira and Suzuki cross-couplings were also confirmed by X-ray crystallography.     

Synthesis and conformational analysis of new troponyl aromatic amino acid

Synthetic peptides are in huge demand in expansion of potential peptide mimics, which may have improved or comparable function as natural one. With these concerns, phenyl bearing aromatic amino acids and peptides has extensively explored, because phenyl residue has high probability in forming stable secondary structure, owing to the presence of an extra stabilizing factor as π–π non-covalent interactions. Apart from phenyl bearing benzenoid aromatic amino acids, a few non-benzenoid aromatic derivatives such as tropolone and related compounds are also occurred in nature, but troponyl containing amino acids and peptides are very poorly understood. Tropolonyl derivatives also contain carbonyl functional group, which may play an important role to provide stable conformation in peptide. Herein we report the synthesis, and conformational analysis of rationally designed new unnatural δ-amino acid, troponyl aminoethylglycine (Tr-aeg), which contains troponyl residue as side chain in flexible aminoethylglycine (aeg) amino acid backbone. We also demonstrate the role of troponyl carbonyl of Tr-aeg residue in hydrogen bonding with adjacent amide NH of their hybrid di/tri-peptides with NMR methods and DFT calculations. In future, Tr-aeg amino acid would be a potential building block in development of promisable peptide mimics.     

Synthesis of 2,3-unsaturated glycosides via metal-free Ferrier reaction

Hexafluoroisopropanol (HFIP) is explored as an effective medium for the synthesis of 2,3-unsaturated glycosides through allylic rearrangement of 3,4,6-tri-O-acetyl glucal. This metal-free, exclusively solvent-promoted Ferrier glycosylation, affords products in good to excellent yields and with good α-selectivity.     

Practical and high stereoselective synthesis of 3-(arylmethylene)isoindolin-1-ones from 2-formylbenzoic acid

Practical and high stereoselective synthesis of 3-(arylmethylene)isoindolin-1-ones is reported. The synthetic method involves the preparation of dimethyl isoindolin-1-one-3-yl-phosphonates by a ‘one-pot’ three-component reaction of 2-formylbenzoic acid with 4-methoxybenzylamine or aminoacetaldehyde dimethyl acetal and dimethyl phosphite under solvent and catalyst free-conditions, followed by a Horner reaction with several aryl aldehydes.     

(3S)-2,2-二甲基-3-苄氧基癸酸的合成

以 (R) pantolactone为原料 ,经还原、羟基保护、环合、开环、脱保护、氧化等 8步反应 ,合成了 (3S) 2 ,2 二甲基 3 苄氧基癸酸 ,总收率为 40 0 % .