Synthesis of new optically active α,α′,β‐trisubstituted‐β‐lactones as monomers for stereoregular biopolyesters

Various optically active (4R)‐alkyloxycarbonyl‐3,3‐dialkyl‐2‐oxetanones as monomers were synthesized from L‐(S)‐malic acid in six steps to prepare a new family of stereopolyesters for biomedical applications. The synthesis began with an esterification followed of a dialkylation in the aim to introduce hydrophobic groups as methyl or reactive group as allyl. Then, a saponification has permitted to obtain the corresponding diacids that reacted with appropriate alcohols to furnish different monoesters. The last and most important step was activation of hydroxyl group of monoesters with the asymmetric carbon configuration inversion according to the Mitsunobu reaction. Thus, this reaction has provided lactones from monoesters with 100% enantiomeric excess which was confirmed by ¹H NMR and by the synthesis of corresponding isotactic and semicrystalline homopolyesters. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015 , 53, 2586–2597     

Fragmentation Mechanism of Trans—α—Aryl—β—enamino Esters

Electron impact-induced fragmentation mechanism of Trans-α-Aryl-β-enamino esters were investigated using mass-analyzed ion kinetic energy (MIKE) spectrometry and high resolution accurate mass data It was found that the main characteristic fragmentations of compounds studied were:an odd electron ion M^ -EtOH was formed by losing a neutral molecule of ethanol;and the skeletal rearrangements took place;and the ring opening reaction happened after losing a carbon monoxide;and the typical McLafferty rearrangement underwent in ester group.The cycliztion reation caused by losing neutral molecule of TsNH2 due to the ortho-effects of substituted group of gromatic ring was also observed.     

An Efficient One-pot Synthesis of β-Amino/β-Acetamido Carbonyl Compounds via ZrCl4-catalyzed Mannich-type Reaction

Zirconium(IV) chloride catalyzed efficient one-pot synthesis of β-amino/β-acetamido carbonyl compounds at room temperature is described. In the presence of ZrCl4, the three-component Mannich-type reaction via a variety of in situ generated aldimines, with various ketones, aromatic aldehydes and aromatic amines in ethanol, led to the formation of β-amino carbonyl compounds and the four-component Mannich-type reaction of aromatic aldehydes with various ketones, acetonitrile and acetyl chloride resulted in the corresponding β-acetamido carbonyl compounds in high to excellent yields. This methodology has also been applied towards the synthesis of dimeric β-amino/β-acetamido carbonyl compounds.     

Water‐Insensitive Synthesis of Poly‐β‐Peptides with Defined Architecture

Biocompatible and proteolysis‐resistant poly‐β‐peptides have broad applications and are dominantly synthesized via the harsh and water‐sensitive ring‐opening polymerization of β‐lactams in a glovebox or using a Schlenk line, catalyzed by the strong base LiN(SiMe₃)₂. We have developed a controllable and water‐insensitive ring‐opening polymerization of β‐amino acid N‐thiocarboxyanhydrides (β‐NTAs) that can be operated in open vessels to prepare poly‐β‐peptides in high yields, with diverse functional groups, variable chain length, narrow dispersity and defined architecture. These merits imply wide applications of β‐NTA polymerization and resulting poly‐β‐peptides, which is validated by the finding of a HDP‐mimicking poly‐β‐peptide with potent antimicrobial activities. The living β‐NTA polymerization enables the controllable synthesis of random, block copolymers and easy tuning of both terminal groups of polypeptides, which facilitated the unravelling of the antibacterial mechanism using the fluorophore‐labelled poly‐β‐peptide.     

TBAF‐Mediated Dimerization Reaction of β,γ‐Unsaturated Arylketones

A simple and high‐yield method for the synthesis of several 1,5‐diaryl‐1,5‐dicarbonyl compounds has been established starting from TBAF‐mediated isomerization and dimerization reaction of β,γ‐unsaturated arylketones (allyl arylketones) with mono‐, di‐, and tri‐methoxy groups, which is derived from allylation of commercially available different benzaldehydes and followed by oxidation of the resulting secondary alcohols.     

Photolysis of α,β‐Epoxyketones: A Green Synthesis of β‐Hydroxyenones through Tandem H‐Abstraction,Ring Cleavage and Isomerisation

The photochemical behavior of various substituted epoxycarbonyl compounds consisting of more than one possible photo‐labile site (i.e. δ‐hydrogen, β‐hydrogen and epoxide ring) has been investigated. These compounds on photo‐irradiation produced the β‐hydroxyenones in an eco‐friendly green approach. Mechanistically, these photo‐transformations have been envisaged to occur via an intramolecular β‐hydrogen abstraction by the carbonyl group of benzoyl moiety to generate the 1,3‐biradical followed by epoxide ring opening that isomerizes into the photoproducts. The photolysis of the probed epoxy ketones didn’t furnish any photoproduct through δ‐hydrogen abstraction, whatsoever. This exclusive preference for β‐H abstraction over δ‐H abstraction by carbonyl group has been vindicated by the MM2 energy mini‐ mized program for the investigated photochemical substrates. The structures of these photoproducts were established from the analysis of their spectral parameters (IR, ¹H/¹³C NMR and Mass) and single crystal X‐ray crystallography data.     

5-雄烯-3β, 7α, 17β-三醇和5-雄烯-3β, 7β, 17β-三醇的合成

以5-雄烯二醇为原料,用微生物转化的方法合成了两个重要的神经甾体5-雄烯-3β, 7α, 17β-三醇和5-雄烯-3β, 7β, 17β-三醇。所用菌种总枝毛霉为我们自己筛选,并首次应用于5-雄烯-3β, 7α, 17β-三醇和5-雄烯-3β, 7β, 17β-三醇的合成中。     

‘Click Synthesis’ of Some Novel O‐Substituted Oximes Containing 1,2,3‐Triazole‐1,4‐diyl Residues as New Analogs of β‐Adrenoceptor Antagonists

The ‘click synthesis’ of some novel O‐substituted oximes, 7a – 7t , which contain 1,2,3‐triazolediyl residues, as new analogs of β‐adrenoceptor antagonists is described (Schemes 1–4). The synthesis of these compounds was achieved in four to five steps. The formation of oximes of 9H‐fluoren‐9‐one and benzophenone, i.e., 9a and 9b , respectively, followed by their reaction with propargyl bromide, afforded O‐propargyl oximes 10a and 10b , respectively, which by a subsequent CuI‐catalyzed Huisgen cycloaddition with prepared β‐azido alcohols 11a – 11j (Schemes 2 and 3), led to the target compounds 7a – 7t in good yields.     

Chemoselective Synthesis of β‐Amino Ester or β‐Lactam via Sonochemical Reformatsky Reaction

A series of β‐amino esters were synthesized by the reaction of N‐tosyl aldimine or N‐hydroxy aldimine with bromoacetate by sonochemical Reformatsky reaction. The β‐N‐hydroxyamino ester was obtained and the formed sensitive hydroxylamino functionality was resistant under the reaction condition. The β‐lactam also was synthesized by the reaction of N‐p‐methoxy aldimine as reacting substrate under this sonochemical Reformatsky reaction condition.     

Phosphoryl group differentiating α‐amino acids from β‐ and γ‐amino acids in prebiotic peptide formation

In recent years β‐amino acids have increased their importance enormously in defining secondary structures of β‐peptides. Interest in β‐amino acids raises the question: Why and how did nature choose α‐amino acids for the central role in life? In this article we present experimental results of MS and ³¹P NMR methods on the chemical behavior of N‐phosphorylated α‐alanine, β‐alanine, and γ‐amino butyric acid in different solvents. N‐Phosphoryl α‐alanine can self‐assemble to N‐phosphopeptides either in water or in organic solvents, while no assembly was observed for β‐ or γ‐amino acids. An intramolecular carboxylic–phosphoric mixed anhydride (IMCPA) is the key structure responsible for their chemical behaviors. Relative energies and solvent effects of three isomers of IMCPA derived from α‐alanine (2a–c), with five‐membered ring, and five isomers of IMCPA derived from β‐alanine (4a–e), with six‐membered ring, were calculated with density functional theory at the B3LYP/6‐31G** level. The lower relative energy (3.2 kcal/mol in water) of 2b and lower energy barrier for its formation (16.7 kcal/mol in water) are responsible for the peptide formation from N‐phosphoryl α‐alanine. Both experimental and theoretical studies indicate that the structural difference among α‐, β‐, and γ‐amino acids can be recognized by formation of IMCPA after N‐phosphorylation. © 2003 Wiley Periodicals, Inc. Int J Quantum Chem 94: 232–241, 2003     

Synthesis of Phenanthrene Derivatives through the Reaction of an α,α‐Dicyanoolefin with α,β‐Unsaturated Carbonyl Compounds

Phenanthrene derivatives were prepared by reacting an α,α‐dicyanoolefin with different α,β‐unsaturated carbonyl compounds resulting from Wittig reaction of ninhydrin and phosphanylidene or condensation of barbituric acid and an aldehyde. The easy procedure, mild and metal‐catalyst free, reaction conditions, good yields, and no need for chromatographic purifications are important features of this protocol. The structures of the product of type 3 and 5 were corroborated spectroscopically (IR, ¹H‐ and ¹³C‐NMR, and EI‐MS). A plausible mechanism for this type of reaction is proposed (Scheme 1).     

Synthesis and Structures of β‐Diketoiminate Complexes of Magnesium

The reaction of the β‐diketoiminate lithium complex (dipp)NacNacLi · OEt₂ ((dipp)NacNac = 2‐((2,6‐diisopropylphenyl)amino)‐4‐((2,6‐diisopropylphenyl)imino)‐pent‐2‐enyl) with iPrMgCl and MgI₂ yield the corresponding (dipp)NacNacMgiPr · OEt₂ ( 1 ) and (dipp)NacNacMgI · OEt₂ ( 2 ). The reaction of 2 with NaBH₄ in diethylether gives (dipp)NacNacMg(μ‐H)₃BH · OEt₂ ( 3 ). The core element of compounds 1 – 3 is a six‐membered ring formed by N(1)–C(1)–C(2)–C(3)–N(2) and magnesium. The structures of 1 and 2 show the β‐diketoiminate backbone in a boat‐conformation with the tetrahedrally coordinated metal center at the prow and the opposing carbon atom at the stern. The magnesium atom in 3 is octahedrally coordinated and out of the β‐diketoiminate plane.     

Rhodium‐catalyzed Asymmetric Hydrogenation of α‐Dehydroamino Ketones: A General Approach to Chiral α‐amino Ketones

Rhodium/DuanPhos‐catalyzed asymmetric hydrogenation of aliphatic α‐dehydroamino ketones has been achieved and afforded chiral α‐amino ketones in high yields and excellent enantioselectives (up to 99 % ee), which could be reduced further to chiral β‐amino alcohols by LiAlH(tBuO)₃ with good yields_. This protocol provides a readily accessible route for the synthesis of chiral α‐amino ketones and chiral β‐amino alcohols.     

Microwave‐Assisted Synthesis of β‐Lactams and Cyclo‐β‐dipeptides

Different cyclo‐β‐dipeptides were prepared from corresponding N‐substituted β‐alanine derivatives under mild conditions using PhPOCl₂ as activating agent in benzene and Et₃N as base. To evaluate β³‐substituent influence, the amino acids 7 – 26 were synthesized, and a β‐lactam formation reaction was carried out instead of cyclo‐β‐dipeptide formation. The crystal structures of three derivatives of cyclo‐β‐peptides and one β‐lactam are presented.     

Base Mediated Aromatization of Carbonyl Condensation Products Derived from 2‐(2‐Bromoprop‐2‐enyl)cyclohexanone Derivatives via ‘Intramolecular Unsaturation Transfer’

Alkylbenzenes are synthesized for the first time from aliphatic hydrocarbons via an one pot, transition metal‐free coupling approach under basic conditions. The method consists of two steps: condensation of 2‐bromoprop‐2‐enyl‐ or 2‐propargylcyclohexanone with alcohols, amines, or amino alcohols, followed by base treatment (Scheme 1). Phenolic ethers and N‐phenylated polyalkyl aromatic compounds are shown to be in the scope of the demonstrated reaction (Table). The proposed mechanism suggests that the unsaturation in another part of the molecule (propargyl‐group equivalent) is transferred into the cyclohexane ring to yield a benzene ring through a series of prototropic shifts.     

Chiral discrimination of β‐3‐homo‐amino acids using the kinetic method

Chiral discrimination of seven enantiomeric pairs of β‐3‐homo‐amino acids was studied by using the kinetic method and trimeric metal‐bound complexes, with natural and unnatural α‐amino acids as chiral reference compounds and divalent metal ions (Cu²⁺ and Ni²⁺) as the center ions. The β‐3‐homo‐amino acids were selected for this study because, first of all, chiral discrimination of β‐amino acids has not been extensively studied by mass spectrometry. Moreover, these β‐3‐homo‐amino acids studied have different aromatic side chains. Thus, the emphasis was to study the effect of the side chain (electron density of the phenyl ring, as well as the difference between phenyl and benzyl side chains) for the chiral discrimination. The results showed that by the proper choice of a metal ion and a chiral reference compound, all seven enantiomeric pairs of β‐3‐homo‐amino acids could be differentiated. Moreover, it was noted that the β‐3‐homo‐amino acids with benzyl side chains provided higher enantioselectivity than the corresponding phenyl ones. However, increasing or decreasing the electron density of the aromatic ring by different substituents in both the phenyl and benzyl side chains had practically no role for chiral discrimination of β‐3‐homo‐amino acids studied. When copper was used as the central metal, the phenyl side chain containing reference molecules (S)‐2‐amino‐2‐phenylacetic acid (L ‐Phg) and (S)‐2‐amino‐2‐(4‐hydroxyphenyl)‐acetic acid (L ‐4′‐OHPhg) gave rise to an additional copper‐reduced dimeric fragment ion, [Cu^I(ref)(A)]⁺. The inclusion of this ion improved noticeably the enantioselectivity values obtained. Copyright © 2010 John Wiley & Sons, Ltd.     

Synthesis of β‐Hydroxy α‐Sulfanyl Esters by Using Nanocrystalline Magnesium Oxide

Aldol‐type reaction between electron deficient aldehydes and sulfonium salts to afford the corresponding β‐hydroxy α‐sulfanyl esters in moderate‐to‐good yields by using nanocrystalline MgO is described. The sulfanyl group is a useful group for further transformations in organic synthesis. Low R_f‐value isomer is anti‐configured as revealed by X‐ray diffraction study and consistent with the assignment of ¹H‐NMR spectrum.     

A New Route to N‐Aryl 2‐Alkenamides,N‐Allyl N‐Aryl 2‐Alkenamides,and N‐Aryl α,β‐Unsaturated γ‐Lactams from N‐Aryl 3‐(Phenylsulfonyl)propanamides

A series of N‐aryl 2‐alkenamides were produced efficiently by treating N‐aryl 3‐(phenylsulfonyl)‐propanamides with potassium tert‐butoxide in THF at 0°C. With out isolation, it was further treated with an additional equivalent of potassium tert‐butoxide and allyl bromide to give N‐allyl N‐aryl 2‐alkenamides in one pot in good yields. Followed by a ring‐closing metathesis reaction, these N‐allyl N‐aryl 2‐alkenamides were respectively converted into corresponding N‐aryl α,β‐unsaturated γ‐lactams in moderate yields.     

Synthesis of ferrocene‐containing N‐aryloxo β‐ketoiminate lanthanide complexes and polymerization of ε‐caprolactone

The synthesis, characterization and ε‐caprolactone polymerization behavior of lanthanide amido complexes stabilized by ferrocene‐containing N‐aryloxo functionalized β‐ketoiminate ligand FcCOCH₂C(Me)N(2‐HO‐5‐Bu^t‐C₆H₃) (LH₂, Fc = ferrocenyl) are described. The lanthanide amido complexes [LLnN(SiMe₃)₂(THF)]₂ [Ln = Nd ( 1 ), Sm ( 2 ), Yb ( 3 ), Y ( 4 )] were synthesized in good yields by the amine elimination reactions of LH₂ with Ln[N(SiMe₃)₂]₃(µ‐Cl)Li(THF)₃ in a 1:1 molar ratio in THF. These complexes were characterized by IR spectroscopy and elemental analysis, and ¹H NMR spectroscopy was added for the analysis of complex 4 . The definitive molecular structures of complexes 1 and 3 were determined by X‐ray diffraction studies. Complexes 1 – 4 can initiate the ring‐opening polymerization of ε‐caprolactone with moderate activity. Copyright © 2011 John Wiley & Sons, Ltd.     

Enantioselective addition of EtzZn to aldehydes catalyzed by chiral aliphatic β‐amino alcohols

This paper describes the preparation of two new optically active aliphatic β‐amino alcohols (R)‐5,5‐dimethyl‐2–(dimethylamino)‐1, 1‐diphenyl‐1‐bersanol (la) and (S)‐8,8‐dimethyl‐2–(dimethylamino)‐1, 1‐diphenyl‐1‐nonanol (1b). They were synthesized by methylation of the corresponding β‐amino alcohols 2a and 2b. Compounds 1a and 1b catalyze the addition of diethylzinc to various aldehydes enantioselectivity. The catalyst structure‐enantioselectivity relationships were discussed.