Total synthesis of two γ-butyrolactone containing compounds (Z,11S)-3,4-trans-11-hydroxy-3-methyldodec-cis-6-en-4-olide and (Z)-3,4-trans-11-oxo-3-methyldodec-cis-6-en-4-olide

The first total synthesis of (Z,11S)-3,4-trans-11-hydroxy-3-methyldodec-cis-6-en-4-olide and (Z)-3,4-trans-11-oxo-3-methyldodec-cis-6-en-4-olide was accomplished using Jacobsen hydrolytic kinetic resolution, Ohira–Bestmann reaction, regioselective alkyne addition to terminal carbon atom of epoxide, intramolecular TEMPO/BAIB mediated oxidative lactonization and partial hydrogenation as the key steps.     

Facile synthesis of (Z)- and (E)-3-allylidene-β-lactams via thermal β-elimination of trans-3-allyl-3-sulfinyl-β-lactams

A competent synthetic route for the synthesis of novel (Z)- and (E)-3-allylidene-β-lactams is described. The strategy involves oxidation of trans-3-allyl-3-phenylthio-β-lactams 1 using sodium metaperiodate (NaIO₄) to diastereomeric trans-3-allyl-3-phenylsulfinyl-β-lactams 2 and 3, which further undergo thermal β-elimination in refluxing carbon tetrachloride to furnish (Z)- and (E)-3-allylidene-β-lactams 5 and 6 in good to excellent yields. The molecular structure of 3b has been established with the help of single crystal X-ray analysis.     

The first stereoselective total synthesis of (3S,4R)-dihydroxy-(6S)-undecyl-α-pyranone and total synthesis of (2S,3R,5S)-(−)-2,3-dihydroxytetradecan-5-olide

The first total synthesis of (3S,4R)-dihydroxy-(6S)-undecyl-α-pyranone 1 and total synthesis of (2S,3R,5S)-(−)-2,3-dihydroxytetradecan-5-olide 2 have been achieved in five steps in a highly stereoselective manner using Maruoka allylation, olefin cross-metathesis, and Sharpless asymmetric dihydroxylation as key steps.     

Synthesis of (E)- and (Z)-α,β-difluorourocanic acid

Horner-Emmons fluoroolefination of an aryl aldehyde followed by introduction of a second fluorine via “FBr” addition provides an original approach to the preparation of 1-alkyl-2-aryl-1,2-difluoroethenes. The utility of this procedure is demonstrated by the preparation of (E and Z)-α,β-difluorourocanic acid.     

Synthesis of (3R,4S,5S,9S)-3,5,9-trihydroxy-4-methylundecanoic acid δ-lactone

Radical-mediated opening of a chiral trisubstituted epoxy alcohol using cp₂TiCl furnished the ‘2-methyl-1,3-diol’ moiety with the desired stereochemistry, which led to a total synthesis of (3R,4S,5S,9S)-3,5,9-trihydroxy-4-methylundecanoic acid δ-lactone 1.     

Host compounds (+)-(2R,3R)-1,1,4,4-tetraphenylbutane-1,2,3,4-tetraol (TETROL) and (2R,3R)-(−)-2,3-dimethoxy-1,1,4,4-tetraphenylbutane-1,4-diol (DMT) with guests o-, m- and p- toluidine: A comparative investigation

In this work, we have compared the host abilities of closely related compounds (+)-(2R,3R)-1,1,4,4-tetraphenylbutane-1,2,3,4-tetraol (TETROL) and (2R,3R)-(?)-2,3-dimethoxy-1,1,4,4-tetraphenylbutane-1,4-diol (DMT) when these were recrystallized from single and mixed toluidine guests. Significant differences in host behaviour and selectivities were revealed and these were explained by means of single crystal diffraction experiments. Thermal analyses were used to determine the relative complex stabilities, and these data correlated exactly with the host selectivity orders for both TETROL and DMT.     

SmI2-induced cyclization of optically active (E)- and (Z)-β-alkoxyvinyl sulfoxides with aldehydes

SmI₂-induced reaction of (E)-β-alkoxyvinyl (R)- and (S)-sulfoxides with aldehydes effected a highly stereoselective intramolecular cyclization to give 2,6-anti-2,3-cis- and 2,6-syn-2,3-trans-tetrahydropyran-3-ols, respectively. The reaction of (Z)-(R)-isomer gave 2,6-syn-2,3-cis-tetrahydropyran-3-ol and a ring-opened product, and that of (Z)-(S)-isomer yielded many products.     

Synthesis of cis- and trans-(±)-3-mercaptoproline and pipecolic acid derivatives via thio-Michael addition

The reactivity of 2,3-dehydroproline and 2,3-dehydropipecolic acid methyl ester derivatives with S-nucleophiles in the thio-Michael addition reaction has been explored. The addition of triphenylmethanethiol and subsequent trityl cleavage led to the corresponding cis- and trans-(±)-3-mercaptoproline and pipecolic acid derivatives in good yields.     

Stereoselective synthesis of (22Z)-25-hydroxyvitamin D2 and (22Z)-1α,25-dihydroxyvitamin D2

Two new vitamin D₂ analogues, (22Z)-25-(OH)-D₂ and (22Z)-1α,25-(OH)₂-D₂, were serendipitously synthesized from vitamin D₂ and using the Julia-Kocienski olefination.     

One-pot synthesis of (Z)-β-sulfonyl enoates from ethyl propiolate

β-Sulfonyl enoates may be synthesized through a one-pot two-step sequence from ethyl propiolate with good to excellent selectivity for the Z isomer. Trialkylamines catalyze thioconjugate additions of aryl thiols, and alkoxides catalyze the addition of aliphatic thiols. Addition of meta-chloroperbenzoic acid (mCPBA) and LiClO₄ to the reaction mixture provides rapid access to the sulfonyl enoates. Yields of the pure Z isomer range from 51-90%.     

The preparation,crystal structure and electrochemistry of (5Z,5′Z)-2,2′-(alkane-α,ω-diylsulfanyldiyl)bis(5-(3-pyridylmethylene)-3,5-dihydro-4H-imidazol-4-ones) and their complexes with cobalt(II) chloride

A series of S-alkylated derivatives of 2-thiohydantoins, containing two 5-(3-pyridylmethylene)-3,5-dihydro-4H-imiazole-4-one fragments joined by polymethylene bridges with different numbers of carbon atoms, was synthesized. The title (5Z,5′Z)-2,2′-(alkane-α,ω-diylsulfanyldiyl)bis(5-(3-pyridylmethylene)-3,5-dihydro-4H-imidazol-4-ones) (L) were obtained by alkylation of 5-(3-pyridylmethylene)-3-phenyl-2-thiohydantoine by 1,2-dibromoethane, 1,6-dibromohexane or 1,10-dibromodecane in DMF in the presence of potassium carbonate. The complexes of ligands L with CoCl₂ · 6H₂O have been synthesized. It is shown that, regardless of the L:CoCl₂ ratio, complexes with LCoCl₂ composition are obtained in all cases. The structure of the cobalt(II) chloride complex with (5Z,5′Z)-2,2′-(ethane-1,2-diyldisulfanyldiyl)bis(5-(3-pyridylmethylene)-3-phenyl-3,5-dihydro-4H-imidazol-4-one) was determined by means of the RSA method. The cobalt atom in this complex has a tetrahedral ligand environment and it is coordinated by two chloride anions and two nitrogen atoms of pyridine fragments, forming a 19-membered metallocycle. Electrochemical investigations of the synthesized ligands and complexes have been made by CVA and RDE methods. It is established that the first stage of reduction for the complexes takes place on the metal, whereas the first stage of oxidation takes place on the coordinated chloride-anions.     

Enantioselective synthesis of (2R,3R)- and (2S,3S)-β-hydroxyornithine

An efficient and short synthesis of (2R,3R)- and (2S,3S)-β-hydroxyornithine 1a-b is described using Sharpless asymmetric dihydroxylation and regioselective nucleophilic opening of a cyclic sulfite as the key steps.     

Preparation of (1R,4S)-4-hydroxycyclopent-2-en-1-yl acetate via Novozym-435® catalyzed desymmetrization of cis-3,5-Diacetoxy-1-cyclopentene

Photooxidation of cyclopentadiene has been carried out in methanol using white light of LED lamp, rose bengal as photo initiator, and compressed air at 0?°C. Under conditions of [thiourea] ? [cyclopentadiene], the consumption of thiourea follows a pseudo-first-order reaction kinetics with half life of 75?±?10?min; corr. coeff. r?=?0.989. Slow addition of the monomer and maintaining excess thiourea concentration in reaction mass improves the yield. cis-3,5-Dihydroxy-1-cyclopentene is acetylated without isolation to obtain cis-3,5-Diacetoxy-1-cyclopentene of high purity (>99%) with overall isolated yield of 30%. Desymmetrization of the diacetate to (1R,4S)-4-hydroxycyclopent-2-en-1-yl acetate has been carried out via enzymatic transesterification with methanol in methyl tert-butyl ether (MTBE) at 5?°C using Novozym-435^®. The enantiomerically pure monoacetate (e.e. >99%) was obtained in 95% isolated yield. The recovered enzyme was reused for more than 10 times without loss in yield and selectivity. The entire protocol does not require purification of final product by chromatography.     

Flavonol 3-O-robinobiosides and 3-O-(2″-O-α-rhamnopyranosyl)-robinobiosides from Sesuvium portulacastrum

Six new flavonol 3-O-robinobiosides and 3-O-(2″-O-α-l-rhamnopyranosyl)-robinobiosides, sesuviosides A-F, were isolated from the aerial portion of Sesuvium portulacastrum together with ecdysterone, adenosine, 2′-O-methyladenosine, and l-tryptophan. The structure elucidations were based on analyses of chemical and spectroscopic data including 1D and 2D-NMR. Sesuviosides A-F and their aglycones exhibited radical scavenging activity using DPPH and ORAC assays.     

π-Extended conjugate phenylacetylenes. Synthesis of 4-[(E) and (Z)-2-(4-ethenylphenyl)ethenyl]pyridine. Dimerization, quaternation and formation of charge-transfer complexes

The conjugate (E)- and (Z)-(4′-pyridylethenyl)-4-phenylethyne (E-4 and Z-4) has been satisfactorily prepared by two different routes: (a) by dehydrohalogenation of 4′-pyridylethenyl-4-phenyl-β-chloroethene; (b) by the Wittig reaction between p-(iodobenzyl)(triphenyl)phosphine ylide and 4-pyridinecarboxaldehyde, E/Z isomer separation, and cross-coupling with 2-methyl-but-3-yn-2-ol followed the propanone elimination. The Glaser oxidative dimerization of (Z)-4 yields (Z,Z)-1,4-di[(4′-pyridylethenyl)-4-phenyl]-buta-1,3-diyne in good yield, (Z,Z)-5. (E,E)-5 was obtained by phase transfer oxidative dimerisation of (E)-4 in presence of their N-methyl salt (E)-10. Mono- and di-N-methylated salts of conjugate (E,E)-5 and (Z,Z)-5, were obtained by quaternation with iodomethane. The (Z,Z)-5 di-N-methylated salt forms charge-transfer complexes with TCNE, TCNQ and TMPD.     

Synthesis of β-chloro α-amino acids: (2S,3R)- and (2S,3S)-3-chloroleucine

The first syntheses of (2S,3R)- and (2S,3S)-3-chloroleucine (3-chloro-d-leucines 1 and 2) have been achieved from d-3-hydroxyleucine and allo-d-3-hydroxyleucine, respectively, through the formation of the corresponding N-Cbz β-lactones, followed by a ring opening promoted by lithium chloride and a debenzylation process.     

Oxidative ring opening of 3-hydroxyquinoline-2,4(1H,3H)-diones into N-(α-ketoacyl)anthranilic acids

N-(α-Ketoacyl)anthranilic acids were prepared by oxidative ring opening of 3-hydroxyquinoline-2,4(1H,3H)-diones by using paraperiodic acid (H₅IO₆) or sodium periodate (NaIO₄). The optimisation of the reaction conditions is described as well as the utilisation of N-(α-ketoacyl)anthranilic acids in the preparation of anthranilic acid hydrochlorides.     

Conversion of γ-substituted bicyclo[2.2.1] (Z)-vinylsulfones to the corresponding (E)-allylsulfones

The preparation of bicyclo[2.2.1] (E)-allylsulfones starting from the corresponding (Z)-vinylsulfones is described. Starting from 2,3-bis(phenylsulfonyl)norbornadiene 1, the Michael addition of organometallic reagents followed by the base catalyzed isomerization affords (E)-allylsulfones in high yields. The procedure allows to obtain vinylidenic norbornenes which are characteristic nuclei of valuable biologically active compounds.     

Studies on Condensed Heterocyclic Compounds(Ⅲ)——Synthesis and Antibacterial Activity of 3-(4-Pyridyl)-6-Alkyl/Aromatic Heterocyclyl-s-Triazolo[3,4-b]-1, 3,4-Thiadiazoles and 1,4-Bis [6-(4-Pyridyl)-s-Triazolo [3,4-b]-1, 3,4-Thiadiazol-3-yl]-n-Butane

In recent years, fused heterocycles have been reported to possess important properties in synthesis and pharmacology. Especially, s-triazolo, 3,4-thiadiazole derivatives have been attracting much attention for chemists and pharmacologists because they show broad spectra of biological activities, such as antifungal, antibacterial, hy-     

Cyclopenta[g]quinazolinone-based inhibitors of thymidylate synthase targeting α-folate receptor overexpressing tumours: synthetic approaches to 4-{N-[(6RS)-2-hydroxymethyl-4-oxo-3,4,7,8-tetrahydro-6H-cyclopenta[g]quinazolin-6-yl]-N-(prop-2-ynyl)amino}benzoic acid

An advanced intermediate for the synthesis of cyclopenta[g]quinazolinone-based antifolates such as (6RS)-CB300945 was prepared by a convergent methodology. The oxo-functionality required for the formation of the C-6-N-10 bond in 4 was introduced in the initial steps of the synthesis, then the tricyclic ring was constructed and finally the propargyl group was introduced using the (propargyl)Co₂(CO)₆⁺ complex without the need to protect the N-3-H or 2-hydroxymethyl functionalities.