Synthesis of N‐Butanoylhomoserine Lactone

Synthesis of N‐butanoylhomoserine lactone has been achieved from trans‐(2S,4R)‐4‐hydroxyproline via the key regioselective Baeyer‐Villiger reaction.     

Thiolactone chemistry for the synthesis of functional silicone‐based amphiphilic co‐networks

A series of amphiphilic co‐networks (ACNs) is prepared in a straightforward way via thiolactone chemistry by crosslinking a multivalent thiolactone‐functional poly(dimethylsiloxane) building block with poly(ethylene glycol) diacrylates. Formation of the networks is triggered by the addition of an amine, of which the nucleophilicity and steric bulk control the curing kinetics. Furthermore, some of the crosslinks can be sacrificed to introduce a fluorescent group or dye via a thia‐Michael addition, without affecting the bulk mechanical properties and swelling capabilities. The obtained ACNs exhibit a unique set of properties because of their nanophase separation, resulting in hydrophilic PEG and hydrophobic PDMS phases. Hence, swelling in both water and organic solvents is observed, of which the extent can be tuned by varying the overall PEG content. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019 , 57, 322–333     

Water dispersible magnetite nanocluster coated with thermo‐responsive thiolactone‐containing copolymer

This work focused on surface modification of magnetite nanoparticle (MNP) with poly(poly(ethylene glycol) monomethyl ether methacylate)‐b‐(poly(N‐isopropylacrylamide)‐st‐poly(thiolactone acrylamide)), PPEGMA‐b‐(PNIPAAm‐st‐PTlaAm), diblock copolymer, synthesized via reversible addition‐fragmentation chain transfer (RAFT) polymerization to obtain the particles having good water dispersible PPEGMA brushes, thermo‐responsive PNIPAAm, and reactive thiolactone groups of PTlaAm. The thiolactone moiety in the copolymer can readily react with amino groups grafted on MNP surface and essentially induced the formation of MNP nanocluster. According to transmission electron microscopy (TEM), the size of the nanocluster ranged between 200 and 500 nm per cluster with 8 to 10 nm in diameter for each particle. Hydrodynamic diameter of the nanocluster significantly decreased as the dispersion temperature increased from 25°C to 45°C due to the shrinkage of thermo‐responsive PNIPAAm when crossing its lower critical solution temperature (LCST). This stable nanocluster might be potentially used as a magnetic carrier for control release of entrapped entities with a thermally triggering mechanism.     

Conformational Analysis and CD Calculations of Methyl‐Substituted 13‐Tridecano‐13‐lactones

Conformational models covering an energy range of 3 kcal/mol were calculated for (13S)‐tetradecano‐13‐lactone ( 3 ), (12S)‐12‐methyltridecano‐13‐lactone ( 4 ), and (12S,13R)‐12‐methyltetradecano‐13‐lactone ( 8 ), starting from a semiempirical Monte‐Carlo search with AM1 parametrization, and subsequent optimization of the 100 best conformers at the 6‐31G*/B3LYP and then the TZVP/B3LYP level of density‐functional theory. CD Spectra for these models were calculated by the time‐dependent DFT method with the same functional and basis sets as for the ground‐state calculations and Boltzmann weighting of the individual conformers. The good correlation of the calculated and experimental spectra substantiates the interpretation of these conformational models for the structure–odor correlation of musks. Furthermore, the application of the quadrant rule in the estimation of the Cotton effect for macrolide conformers is critically discussed.     

Unexpected Ring Expansion of the (3aS,6aR)‐γ‐Thiolactone Moiety during the Introduction of the (+)‐Biotin Side Chain

The reaction of vinylmagnesium bromide with the (3aS,6aR)‐γ‐thiolactone 2 in THF afforded, after unexpected ring expansion of the γ‐thiolactone moiety, the seven‐membered‐ring ketone 5 in excellent yield, instead of the expected tertiary alcohol 3 .     

Tailored Thiol‐Functional Polyamides: Synthesis and Functionalization

In this article, a synthetic concept for the preparation of polyamides with functional side groups is described. First, the synthesis of a bis(thiolactone) monomer is shown in a concise three‐step route from itaconic acid and DL‐homocysteine thiolactone. The reactivity of the resulting bis(thiolactone) toward hexyl amine is examined. Next, the bis(thiolactone) is reacted as A,A‐type monomer with different B,B‐type comonomers (1,12‐diaminododecane and 1,3‐bis(aminopropyl)tetramethyldisiloxane). Ring opening of the thiolactones by the diamines leads to polyamides with pendant thiol groups. Using two diamines in different ratios, the properties of the resulting polyamides are tuned (thermal properties are determined) and different molecular weights are acquired. Subsequently, the thiol groups are reacted with methyl acrylate via Michael addition to functionalize the polyamides. Functionalization of thiol‐functional polyamides using poly(ethylene glycol) monomethyl ether (mPEG) acrylates ( = 480 and 1700 g mol⁻¹) results in water‐soluble amphiphilic poly­amides with molecular weights higher than 10 000 g mol⁻¹.

     

One‐pot synthesis of soluble and fluorescent aliphatic hyperbranched poly(amide‐imide) with solvent‐dependent emission

Aliphatic hyperbranched poly(amide‐imide) was facilely prepared by employing a functional thiolactone‐maleimide monomer. Highly efficient, selective and quantitative properties of amine‐maleimide Michael addition and aminolysis of a thiolactone guaranteed the generation of an ABB' thiol‐yne intermediate without side products, followed by consecutive thiol‐yne click reaction in one‐pot. The hyperbranched structure of the poly(amide‐imide) was confirmed by NMR spectroscopy and triple‐detector GPC/SEC analysis. Additionally, due to the presence of aminosuccinimide fluorophores and intrinsic physical property of hyperbranched polymers, this aliphatic hyperbranched poly(amide‐imide) possessed solvent‐dependent emission and presented good solubility in various organic solvents. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017 , 55, 2053–2060     

Synthesis of new hydrolyzable polyurethanes from L‐gulonic acid‐derived diols and diisocyanates

New polyurethanes with lactone groups in the pendants and main chains were synthesized by the polyaddition of two kinds of L ‐gulonolactone‐derived diols (2,3‐O‐isopropylidene‐L ‐gulono‐1,4‐lactone and 5,6‐O‐isopropylidene‐L ‐gulono‐1,4‐lactone) with hexamethylene diisocyanate and methyl (S)‐2,6‐diisocyanatohexanoate and by the subsequent deprotection of isopropylidene groups. They were hydrolyzed more quickly than the polyurethane derived from methyl β‐D ‐glucofuranosidurono‐6,3‐lactone in a phosphate buffer solution, the pH value of which was 8.0, at 27 °C. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 40: 4158–4166, 2002     

Facile synthesis of 2‐alkylthio‐5‐phenylmethylene‐4H‐imidazol‐4‐ones

2‐Alkylthio‐5‐phenylmethylidene‐4H‐imidazol‐4‐ones 4 were synthesized by S‐alkylation of 2‐thioxo‐3‐alkyl(aryl)‐4‐imidazolidinones 3 , which were obtained via cyclization of isothiocyanates 2 with aliphatic(aromatic) primary amines. © 2003 Wiley Periodicals, Inc. Heteroatom Chem 14:348–351, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10160     

Synthesis of Bis(imidazole‐2‐thion‐4‐yl)phosphanes

Novel bis(imidazole‐2‐thion‐4‐yl)‐ phosphanes ( 2a–d ) were synthesized via lithiation of the precursor imidazole‐2‐thiones followed by the phosphanylation reaction. Oxidation of bis(imidazole‐2‐thion‐4‐yl)phosphane 2b–d with elemental sulfur and selenium led selectively and in good yields to the P‐thio ( 3b–d ) and P‐seleno ( 4c ) derivatives of bis(imidazole‐2‐thion‐4‐yl)phosphanes, respectively. The treatment of 2a,c with phosphorus trichloride gives the corresponding P‐chloro derivatives 5a,c . These compounds were unambiguously characterized by elemental analyses, spectroscopic and spectrometric methods, in addition by single‐crystal X‐ray structure analysis in the case of 2d . © 2012 Wiley Periodicals, Inc. Heteroatom Chem 00:1–7, 2012; View this article online at wileyonlinelibrary.com . DOI 10.1002/hc.21043     

An improved asymmetric total synthesis of (+)-biotin via the enantioselective desymmetrization of a meso-cyclic anhydride mediated by cinchona alkaloid-based sulfonamide

The highly enantioselective total synthesis of (+)-biotin 1 via the Hoffmann–Roche lactone–thiolactone strategy has been achieved starting from cis-1,3-dibenzyl-2-imidazolidone-4,5-dicarboxylic acid 2 with an overall yield of 35%. Two contiguous stereogenic centers at C-3a and C-6a were established through a rapid cinchona alkaloid-based sulfonamide-mediated enantioselective alcoholysis of meso-cyclic anhydride 3 to afford (4S,5R)-cinnamyl hemiester 4h, the direct precursor to (3aS,6aR)-lactone 5 with high enantioselectivity. A one-pot installation of the 4-carboxybutyl side chain was accomplished by a Fukuyama coupling reaction of (3aS,6aR)-thiolactone 6 with the organozinc reagent prepared from ethyl 5-bromopentanoate.     

Novel,organosoluble, light‐colored fluorinated polyimides based on 2,2′‐bis(4‐amino‐2‐trifluoromethylphenoxy)biphenyl or 2,2′‐bis(4‐amino‐2‐trifluoromethylphenoxy)‐1,1′‐binaphthyl

Two series of fluorinated polyimides were prepared from 2,2′‐bis(4‐amino‐2‐trifluoromethylphenoxy)biphenyl ( 2 ) and 2,2′‐bis(4‐amino‐2‐trifluoromethylphenoxy)‐1,1′‐binaphthyl ( 4 ) with various aromatic dianhydrides via a conventional, two‐step procedure that included a ring‐opening polyaddition to give poly(amic acid)s, followed by chemical or thermal cyclodehydration. The inherent viscosities of the polyimides ranged from 0.54 to 0.73 and 0.19 to 0.36 dL/g, respectively. All the fluorinated polyimides were soluble in many polar organic solvents, such as N,N‐dimethylacetamide and N‐methylpyrrolidone, and afforded transparent and light‐colored films via solution‐casting. These polyimides showed glass‐transition temperatures in the ranges of 222–280 and 257–351 °C by DSC, softening temperatures in the range of 264–301 °C by thermomechanical analysis, and a decomposition temperature for 10% weight loss above 520 °C both in nitrogen and air atmospheres. The polyimides had low moisture absorptions of 0.23–0.58%, low dielectric constants of 2.84–3.61 at 10 kHz, and an ultraviolet–visible absorption cutoff wavelength at 351–434 nm. Copolyimides derived from the same dianhydrides with an equimolar mixture of 4,4′‐oxydianiline and diamine 2 or 4 were also prepared and characterized. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 2416–2431, 2004     

Alkyne‐Mediated Approach to the Synthesis of (4R,5R)‐5‐Hydroxy‐4‐decanolide and (−)‐Muricatacin

The asymmetric synthesis of two naturally occurring 5‐hydroxy‐γ‐butyrolactones, (4R,5R)‐5‐hydroxy‐4‐decanolide ( 1a ) and (?)‐muricatacin ( 2 ), is described using a general alkyne‐mediated strategy. The key steps involved are Sonogashira coupling for the desired carbon‐chain extension followed by Sharpless asymmetric dihydroxylation to construct the hydroxy‐lactone framework.     

Total Synthesis of (−)‐Salvinorin A

Salvinorin A ( 1 ) is natural hallucinogen that binds the human κ‐opioid receptor. A total synthesis has been developed that parlays the stereochemistry of l ‐(+)‐tartaric acid into that of (?)‐ 1 via an unprecedented allylic dithiane intramolecular Diels–Alder reaction to obtain the trans‐decalin scaffold. Tsuji allylation set the C9 quaternary center and a late‐stage stereoselective chiral ligand‐assisted addition of a 3‐titanium furan upon a C12 aldehyde/C17 methyl ester established the furanyl lactone moiety. The tartrate diol was finally converted into the C1,C2 keto‐acetate.     

Formation of a leuco Spirolactone from 4‐(2‐Carboxyphenyl)‐7‐diethylamino‐4′‐dimethylamino‐1‐benzopyrylium: Design of a Phase‐Change Thermochromic System Based on a Flavylium Dye

A phase‐change thermochromic system was designed through the reversible transformation of the 4‐substituted flavylium dye 4‐(2‐carboxyphenyl)‐7‐diethylamino‐4′‐dimethylamino‐1‐benzopyrylium into its leuco form, in the presence of a developer (ethyldiisopropylamine) and a suitable solvent (e.g., acetonitrile, n‐pentadecanonitrile). The leuco form of the flavylium‐based dye is a spirolactone species whose ring opens at low temperature (below the solvent melting point) to form the blue flavylium cation. Decarboxylation of the lactone to give 4‐phenyl‐7‐diethylamino‐4′‐dimethylamino‐1‐benzopyrylium was observed upon irradiation of the system with UV light, erasing the thermochromic effect.     

Two‐Step Synthesis of Multifunctional γ‐Lactams from γ‐Lactone

We present herein an efficient and rapid method for the synthesis of N,1‐dialkyl‐4‐(2‐hydroxyethyl)‐5‐oxopyrrolidine‐3‐carboxamides based on the conversion of γ‐lactone to γ‐lactam via the conjugate addition of primary amines to an ethyl α‐functionalized acrylate followed by intramolecular cyclization.     

The antitumour drug 7‐ethyl‐10‐hydroxycamptothecin monohydrate and its solid‐state hydrolysis mechanism on heating

7‐Ethyl‐10‐hydroxycamptothecin [systematic name: (4S)‐4,11‐diethyl‐4,9‐dihydroxy‐1H‐pyrano[3′,4′:6,7]indolizino[1,2‐b]quinoline‐3,14(4H,12H)‐dione, SN‐38] is an antitumour drug which exerts activity through the inhibition of topoisomerase I. The crystal structure of SN‐38 as the monohydrate, C₂₂H₂₀N₂O₅·H₂O, reveals that it is a monoclinic crystal, with one SN‐38 molecule and one water molecule in the asymmetric unit. When the crystal is heated to 473 K, approximately 30% of SN‐38 is hydrolyzed at its lactone ring, resulting in the formation of the inactive carboxylate form. The molecular arrangement around the water molecule and the lactone ring of SN‐38 in the crystal structure suggests that SN‐38 is hydrolyzed by the water molecule at (x, y, z) nucleophilically attacking the carbonyl C atom of the lactone ring at (x − 1, y, z − 1). Hydrogen bonding around the water molecules and the lactone ring appears to promote this hydrolysis reaction: two carbonyl O atoms, which are hydrogen bonded as hydrogen‐bond acceptors to the water molecule at (x, y, z), might enhance the nucleophilicity of this water molecule, while the water molecule at (−x, y + , −z), which is hydrogen bonded as a hydrogen‐bond donor to the carbonyl O atom at (x − 1, y, z − 1), might enhance the electrophilicity of the carbonyl C atom.     

The unusual ability of α‐angelicalactone to form adducts: A kinetic approach

Since α‐angelicalactone (AAL) substantially inhibits the formation of tumors, here its chemical reactivity was compared with that of carcinogenic lactones. Investigation of the electrophilic potential of AAL was carried out by studying the capacity of this lactone to form adducts with NBP, 4‐(p‐nitrobenzyl)pyridine, a substrate with nucleophilic characteristics similar to DNA bases. The formation of the AAL–NBP adduct occurs about 900,000‐fold faster than with β‐propiolactone, the most effective carcinogenic lactone (ΔG^#₃₅ = 52 and 87 kJ mol^?1, respectively). A stopped‐flow technique was required for this reaction to be monitored. It was concluded that the formation of AAL–NBP adducts takes place through an entropy‐strain‐catalyzed mechanism caused by early lactone ring cleavage. The kinetic results are consistent with the AAL potential as a chemoprotective agent. © 2007 Wiley Periodicals, Inc. Int J Chem Kinet 39: 591–594, 2007     

Synthesis of Nitrogen‐Containing Derivatives of (18α,19β)‐19‐Hydroxy‐2,3‐secooleanane‐2,3,28‐trioic Acid 28,19‐Lactone

The object of this study is the interaction of the cyclic anhydride 2 of (18α,19β)‐19‐hydroxy‐2,3‐secooleanane‐2,3,28‐trioic acid 28,19‐lactone ( 1 ) with primary and secondary amines. It was shown that the products of steric control (the corresponding 2‐amino‐2‐oxo‐3‐oic acids=2‐amides) were formed solely upon the opening of the anhydride cycle by secondary amines (Scheme 2), whereas the interaction with primary amines yielded a mixture of isomeric amides (Scheme 10). In the latter case, the solvent provided a noticeable effect on the reaction selectivity, which was demonstrated in the case of 4‐methoxybenzylamine. The interaction between the resulting 3‐amides and oxalyl chloride yielded the corresponding cyclic imides, whereas under these conditions, 2‐amides formed spiropyrrolidinetriones (Scheme 4).     

Semisynthesis and absolute configuration of a novel rearranged 19,20‐δ‐lactone (9βH)‐pimarane diterpene

Annonalide (3β,20‐epoxy‐3α,16‐dihydroxy‐15‐oxo‐7‐pimaren‐19,6β‐olide, C₂₀H₂₆O₆, 1 ) is the major (9βH)‐pimarane diterpene isolated from tubers of Cassimirella ampla, and it exhibits cytotoxic properties upon interaction with ctDNA. We have prepared new derivatives of 1 by modification of the (9βH)‐pimarane backbone and report here the semisynthesis and absolute configuration of a novel rearranged 19,20‐δ‐lactone (9βH)‐pimarane. Our approach was the reduction of the carbonyl groups of 1 with sodium borohydride, at positions C15 (no stereoselectivity) and C3 (stereoselective reduction), followed by rearrangement of the 6,19‐γ‐lactone ring into the six‐membered 19,20‐δ‐lactone ring in 4a (3β,6β,16‐trihydroxy‐7‐pimaren‐19,20β‐olide monohydrate, C₂₀H₃₀O₆·H₂O). The absolute structure of the new compound, 4a , was determined unambiguously with a Flack parameter x of −0.01 (11), supporting the stereochemistry assignment of 1 redetermined here. Besides the changes in the pattern of covalent bonds caused by reduction and lactone rearrangement, the conformation of one of the three fused cyclohexane rings is profoundly different in 4a , adopting a chair conformation instead of the boat shape found in 1 . Furthermore, the intramolecular hydrogen bond present in 1 is lost in new compound 4a , due to hydrogen bonding between the 3‐OH group and the solvent water molecule.