Microbial oxygenation of dialkylbenzenes (I)

The use of the microorganism Sporotrichum sulfurescens (ATCC 7159) to oxygenate organic molecules has been extended to several dialkylbenzenes. Oxygenation of 1,4-di-t-butylbenzene (1) gave 4-t-butyl(1-hydroxy-2-methyl)isopropylbenzene (2) and 1,4-di-(1-hydroxy-2-methyl)isopropylbenzene (3); of 1,4-diisopropylbenzene (4) gave (R,R)-1,4-di-(1-hydroxy)isopropylbenzene (5); of 1,3-diisopropylbenzene (6) gave 1,3-di-(2-hydroxy)isopropylbenzene (7), 3-(1-hydroxy)isopropyl-(2-hydroxy)isopropylbenzene (8), and 1,3-di-(1-hydroxy)isopropylbenzene (9); and of p-isobutylisopropylbenzene (20) gave 1-(p-2-hydroxyisopropylphenyl)-2-methylpropan-2-ol (15) and 1-(p-1-hydroxyisopropylphenyl)-2-methylpropan-2-ol (16). Monohydroxydialkylbenzenes also served as useful substrates in this reaction as suggested by the fact that 2 is an intermediate in the formation of 3 from 1. Oxygenation of 1-(p-isopropylphenyl)-2-methylpropan-2-ol (14), conveniently prepared from 2-(p-isopropylphenyl)propene (12) via oxygenative isomerization with thallium trinitrate to 13 followed by addition of methyl magnesium bromide, gave 15 and 16. Oxygenation of 2-(p-isobutylphenyl)propan-2-ol (18) gave 15, 2-(p-isobutylphenyl)-propan-1,2-diol (21), and 1-(p-2-hydroxyisopropylphenyl)-2-methylpropan-3-ol (22). Compound 16, obtained from substrate 14, was converted to (2R)-2-[4-(2-hydroxy-2-methylpropyl)phenyl]propionic acid (11), the enantiomer of a metabolite of the antiinflammatory agent, 2-(4-i-butyl)phenylpropionic acid (10).     

Acylated hydroxycinnamic acid glucosides from flowers of Telekia Speciosa

One new derivative of ferulic acid (1), two new caffeic acid derivatives (2 and 3) and three known derivatives of caffeic acid: 6-O-(E)-caffeoyl-glucopyranose (4), (E)-caffeic acid 4-O-β-glucopyranoside (5) and 5-caffeoylquinic acid (chlorogenic acid, 6) were isolated from a butanolic fraction of extract from Telekia speciosa flowers. Moreover, the flavonol glucoside–patulitrin (7) was identified in the analyzed extract. Structures of (E)-ferulic acid 4-O-β-(6-O-2-hydroxyisovaleryl)-glucopyranoside (1), (E)-caffeic acid 4-O-β-(6-O-2-hydroxyisovaleryl)-glucopyranoside (2) and (E)-caffeic acid 4-O-β-(6-O-3-hydroxy-2-methylpropanoyl)-glucopyranoside (3) were elucidated by 1D and 2D NMR, HRESIMS and other spectral analyses.     

Synthesis of 2- (and 6-) -dithian-2-yluracil nucleosides and their conversion into nucleoside derivatives

Addition of 2,2′-anhydro-[1-(3-O-acetyl-5-O-trityl-β-D-arabinofuranosyl)uracil] (1) to excess 2-litho-1,3-dithiane (2)in oxolane at ?78° gave 2-(1,3-dithian-2-yl)-1-(5-O-trityl-β-D-arabinofuranosyl)-4(1H)pyrimidinone (3), O²,2′-anhydro-5,6-di-hydro-6-(S)-(1,3-dithian-2-yl)-5′-O-trityluridine (4), and 2-(1,4-dihydroxybutyl)-1,3-dithiane (5) in yields of 15, 30, and 10% respectively. The structure of 3 was proved by its hydrolysis in acid to give 2-(1,3-dithian-2-yl)-4-pyrimidinone (6) and arabinose, and by desulfurization with Raney nickel to yield the known 2-methyl-1-(5-O-trityl-β-D-arabinofuranosyl)-4(1H)-pyrimidinone (7). Detritylation of 3 without glycosidic cleavage could only be effected by prior acetylation to 1-(2,3-di-O-acetyl-5-O-trityl-β-D-arabinofuranosyl)-2-(1,3-dithian-2-yl)-4(1H)-pyrimidinone (8) which, after treatment with acetic acid at room temperature for 65 h followed by the action of sodium methoxide gave 2-(1,3-dithian-2-yl)-1-β-D-arabinofuranosyl-4(1H)-pyrimidinone (10) in 45% yield. Detritylation of 4 in boiling acetic acid gave 5,6-dihydro-6-(S)-(1,3-dithian-2-yl)-1-β-D-arabinofuranosyluracil (12) and 3-[(S)-1-(1,3-dithian-2-yl)]propionamido-(1,2-dideoxy-β-D-arabinofurano)-[1,2-d]-2-oxazolidinone (13) in 10 and 90% yields, respectively. When 12 was kept in water or methanol for 7 days, quantitative conversion into 13 occurred. Acid hydrolysis of 12 afforded arabinose and 5,6-di-hydro-6-(1,3-dithian-2-yl)uracil (14), which was desulfurized with Raney nickel to the known 5,6-dihydro-6-methyluracil (15). Treatment of 13 with trifluoroacetic anhydride-pyridine yielded 77% of the cyano derivative 17. Similar dehydration of 3-(R)-1-methylpropionamido-(1,2-dideoxy-β-D-arabinofurano)-[1,2-d]-2-oxalidinone (18), obtained by desulfurization of 13, gave 60% of the nitrile 19. Hydrogenation of 19 over platinum oxide in acetic anhydride gave the acetamide derivative 20 in 95% yield. Nitrobenzoylation of 13 gave 3-[(S)-1-(1,3-dithian-2-yl)]cyanomethyl-3,5-di-O-p-nitrobenzoyl-(1,2-dideoxy-β-D-arabinofurano)-[1,2-d]-2-oxazolidinone (22), which was converted in 37% yield by treatment with methyl iodide in dimethyl sulfoxide into the aldehyde 24, characterized as the semicarbazone 25. The purification of 5 and its characterization as 2-(1,4-di-O-p-nitrobenzoylbutyl)-1,3-dithiane (27) is described.     

Chemical constituents from Saussurea licentiana Hand.-Mazz

Chemical investigation of Saussurea licentiana led to the isolation of ten compounds, and their structures were identified to be dia-aurantiamide acetate (1), (+)-pinoresinol 4-O-β-D-glucoside (2), encelin (3), apigenin (4), luteolin (5), jaceosidin (6), luteolin -7-O-β-D- glucopyranoside (7), α-amyrin (8), β-amyrin (9), taraxasterol (10) on the basis of mass and NMR spectra. This is the first report on the occurrence of compounds 1, and 2 in the genus Saussurea while 1 is reported for the first time from Asteraceae. This work also represents the first phytochemical work on the whole plants of S. licentiana.     

Enantioselective microbial reduction of 6-oxo-8-[4-[4-(2-pyrimidinyl)-1-piperazinyl]butyl]-8-azaspiro[4.5]decane-7,9-dione: Cloning and expression of reductases

The enantioselective microbial reduction of 6-oxo-8-[4-[4-(2-pyrimidinyl)-1-piperazinyl]butyl]-8-azaspiro[4.5]decane-7,9-dione (1) to either of the corresponding (S)- and (R)-6-hydroxy-8-[4-[4-(2-pyrimidinyl)-1-piperazinyl]butyl]-8-azaspiro[4.5]decane-7,9-diones (2 and 3, respectively) is described. The NADP⁺-dependent (R)-reductase (RHBR) which catalyzes the reduction of 6-ketobuspirone (1) to (R)-6-hydroxybuspirone (3) was purified to homogeneity from cell extracts of Hansenula polymorpha SC 13845. The subunit molecular weight of the enzyme is 35,000 kDa based on sodium dodecyl sulfate gel electrophoresis and the molecular weight of the enzyme is 37,000 kDa as estimated by gel filtration chromatography. (R)-reductase from H. polymorpha was cloned and expressed in Escherichia coli. To regenerate the cofactor NADPH required for reduction we have cloned and expressed the glucose-6-phosphate dehydrogenase gene from Saccharomyces cerevisiae in E. coli. The NAD⁺-dependent (S)-reductase (SHBR) which catalyzes the reduction of 6-ketobuspirone (1) to (S)-6-hydroxybuspirone (2) was purified to homogeneity from cell extracts of Pseudomonas putida SC 16269. The subunit molecular weight of the enzyme is 25,000 kDa based on sodium dodecyl sulfate gel electrophoresis. The (S)-reductase from P. putida was cloned and expressed in E. coli. To regenerate the cofactor NADH required for reduction we have cloned and expressed the formate dehydrogenase gene from Pichia pastoris in E. coli. Recombinant E. coli expressing (S)-reductase and (R)-reductase catalyzed the reduction of 1 to (S)-6-hyroxybuspirone (2) and (R)-6-hyroxybuspirone (3), respectively, in >98% yield and >99.9% e.e.     

Sulfur-containing constituents and one 1H-pyrrole-2-carboxylic acid derivative from pineapple [Ananas comosus (L.) Merr.] fruit

Two sulfur-containing compounds, (S)-2-amino-5-((R)-1-carboxy-2-((E)-3-(4-hydroxy-3-methoxyphenyl)allylthio)ethyl-amino)-5-oxopentanoic acid (1) and (S)-2-amino-5-((R)-1-(carboxymethylamino)-3-((E)-3-(4-hydroxyphenyl)allylthio)-1-oxopropan-2-ylamino)-5-oxopentanoic acid (2), and one 1H-pyrrole-2-carboxylic acid derivative, 6-(3-(1H-pyrrole-2-carbonyloxy)-2-hydroxypropoxy)-3,4,5-trihydroxy-tetrahydro-2H-pyran-2-carboxylic acid (3), together with eighteen known phenolic compounds, were isolated from the fruits of pineapple. Their structures were elucidated by a combination of spectroscopic analyses. Some of these compounds showed inhibitory activities against tyrosinase. The half maximal inhibitory concentration values of compounds 1, 4, 5, 6, 7 are lower than 1 mM. These compounds may contribute to the well-known anti-browning effect of pineapple juice and be potential skin whitening agents in cosmetic applications.     

Two pairs of new dihydrobenzophenanthridine alkaloid isolated from the root of Macleaya cordata

Two pairs of dihydrobenzophenanthridine alkaloid, named (±)(S)-6-((R)-1-hydroxyethy) dihydrochelerythrine (1a, 1b) and (±)(S)-6-((R)-1-hydroxyethyl)dihydro-sangunarine (2a, 2b) were isolated from the root of Macleaya cordata. Their chemical structures were elucidated by analysis of the spectroscopic data including one-dimensional (1D) and two-dimensional (2D) NMR spectra, and were further confirmed by X-ray crystallographic analysis.     

N-Acetyldopamine derivatives from Periostracum Cicadae

Five new N-acetyldopamine (NADA) derivatives (1–5) and one known NADA quinone methide (6) were isolated from Periostracum Cicadae (the cast-off shell of the cicada Cryptotympana pustulata Fabricius), which is known as chantui in China and is used in traditional Chinese medicine to treat soreness of the throat, hoarseness, itching, and spasms. By combined analysis of one-dimensional and two-dimensional nuclear magnetic resonance (NMR) spectroscopy, mass spectrometry, CD spectra, and chemical evidence, the structures of the isolated compounds were established as (R)-N-(2-(3,4-dihydroxyphenyl)-1-ethoxy-2-oxoethyl)acetamide (1), (1R,2R)-N-(1,2-diethoxy-2-(3,4-dihydroxyphenyl)-ethyl)acetamide (2), (R)-N-(1-acetamido-2-ethoxy-2-(3,4-dihydroxyphenyl)-ethyl)acetamide (3), (1R,2R)-N-(2-(3,4-dihydroxyphenyl)-2-ethoxy-1-methoxyethyl)acetamide (4), (1S,2S)-N-(2-(3,4-dihydroxyphenyl)-2-ethoxy-1-methoxyethyl)acetamide (5), and (R)-N-(2-(3,4-dihydroxyphenyl)-2-methoxyethyl)acetamide (6).     

Oligosaccharides from “standardized intermediates”. The 2-amino-2-deoxy- d-galactose analog of the blood-group O(H) determinant,type 2, and its precursors

The selectively benzylated glycoside allyl 2-acetamido-4,6-di-O-benzyl-2-deoxy-β- d-galactopyranoside ( 4) was prepared from the corresponding derivative of 2-acetamido-2-deoxy- d-glucose via the p-bromobenzenesulfonate and the benzoate. 2-O-Benzoyl-3,4,6-tri-O-benzyl-α- d-galactopyranosyl chloride ( 10) was obtained from allyl 6-O-benzyl-2-O-(2-butenyl)-α- d-galactopyranoside via known intermediates. To complete the sequence, the 1-propenyl 3,4,6-tri-O-benzyl galactoside was successively converted into the 2-benzoate, the free sugar, and the chloride 10. A fully protected form ( 11) of the trisaccharide α- l-Fucp-(1→2)-β- d-Galp-(1→4)- d-GalNAc was then synthesized by coupling 10 to 4, partially deblocking the disaccharide product, and l-fucosylating the resulting intermediate. Cleavage of the O-benzyl groups from 11, with concomitant saturation of the allyl group, gave the propyl β-glycoside of the unsubstituted trisaccharide.     

Active, water-insoluble derivatives of D-glucose oxidase and alginic acid, chitin, and Celite

Treatment of 2-benzimidazolemethanol (4) with methanesulfonyl chloride and pyridine in chloroform afforded 2-(chloromethyl)-1-(methylsulfonyl)benzimidazole (6), which was also prepared by methanesulfonylation of 2-(chloromethyl)benzimidazole. Methanesulfonylation of α-(2-benzimidazolyl)benzyl alcohol (8) in chloroform yielded 2-(α-chlorobenzyl)-1-(methylsulfonyl)benzimidazole. 1-(Methylsulfonyl)-2-benzimidazolemethanol was obtained on methanesulfonylation of 4 pyridine at 0°, and α-[1-(methylsulfonyl)-2-benzimidazolyl]benzyl alcohol (12) was prepared from 8 by using the same reaction conditions. The reaction of 1-acetyl-2-(chloromethyl)-benzimidazole with silver methanesulfonate in benzene gave 1-acetyl-O-(methylsulfonyl)-2-benzimidazolemethanol. Compound 6 has some antitumor activity in the KB cell-culture system, and some antibacterial activity in the Staphylococcus aureus test-system; it is also active in preventing anaphylactic shock in a mouse test-system.     

Diarylheptanoids from Curcuma comosa

Three new diarylheptanoids, designated 1-(3,4-dihydroxyphenyl)-7-(4-hydroxyphenyl)-(6E)-6-hepten-3-ol (1), 1-(3-hydroxyphenyl)-7-(3,4-dihydroxyphenyl)-3-methoxy-(6E)-6-heptene (2), (3R, 5R)-1-(3,4-dihydroxyphenyl)-7-phenyl-heptane-3,5-diol (3) and three known compounds, were isolated from rhizomes of Curcuma comosa. Structures of the compounds were determined by spectroscopic data analysis.     

Chemical constituents from Alnus mandshurica (Callier) Hand.-Mazz. and their chemotaxonomic significance

A new phenol compound, (9S)-9-hydroxy-9-[(2-hydroxyphenyl)methoxy]-nonanoic acid methyl ester (1) was isolated from the stem bark of Alnus mandshurica (Callier) Hand.-Mazz., along with eight known compounds (2–9). The structure of compound 1 was determined by spectral analyses, including HR-ESI-MS, 1D and 2D NMR (COSY, HMQC and HMBC) experiments. All the isolated compounds were reported for first time from A. mandshurica. Furthermore, compounds 3–9 were found in the family Betulaceae for the first time.     

Oxidation of 1,4-alkanediols into γ-lactones via γ-lactols using Rhodococcus erythropolis as biocatalyst

Whole cells of Rhodococcus erythropolis DSM 44534 grown on ethanol, (R)- and (S)-1,2-propanediol were used for biotransformation of racemic 1,4-alkanediols into γ-lactones. The cells oxidized 1,4-decanediol (1a) and 1,4-nonanediol (2a) into the corresponding γ-lactones 5-hexyl-dihydro-2(3H)-furanone (γ-decalactone, 1c) and 5-pentyl-dihydro-2(3H)-furanone (γ-nonalactone, 2c), respectively, with an EE(R) of 40–75%. The transient formation of the γ-lactols 5-hexyl-tetrahydro-2-furanol (γ-decalactol, 1b) and 5-pentyl-tetrahydro-2-furanol (γ-nonalactol, 2b) as intermediates was observed by GC–MS. 1,4-Pentanediol (3a) was transformed into 5-methyl-dihydro-2(3H)-furanone (γ-valerolactone, 3c) whereas (R)- and (S)-2-methyl-1,4-butanediol (4a) was converted to the methyl-substituted γ-butyrolactones 4-methyl-dihydro-2(3H)-furanone (4c₁) and 3-methyl-dihydro-2(3H)-furanone (4c₂) in a ratio of 80:20 with a yield of 55%. Also cis-2-buten-1,4-diol (5a) was transformed resulting in the formation of 2(5H)-furanone (γ-crotonolactone, 5c). At the higher pH values of 8.8 the yield of lactone formed was improved; however, the enatiomeric excesses were slightly higher at the lower pH of 5.2.     

The synthesis of new deoxynitroinositols by cyclization of 6-deoxy-3-O-methyl-6-nitro-d-allose and -l-talose

6-Deoxy-3-O-methyl-6-nitro-d-allose (5) and -l-talose (6) were synthesized from 1,2-O-isopropylidene-3O-methyl-α-d-allofuranose (1) by the nitromethane method via their furanoid, 1,2-O-isopropylidene derivatives (2 and 3). The barium hydroxide-catalyzed cyclization of the free nitrohexoses (5 and 6) was investigated. Under conditions favoring kinetic control (pH ～8, 0°), 5 gave mainly 1d-5-deoxy-2-O-methyl-5-nitro-allo-inositol (7), with the 1l-epi-1 (8) and epi-6 (9) stereoisomers as minor products. Compound 6 afforded a high yield of the myo-5-isomer (11); the 1l-allo-5 (13) and 1d-epi-1 (14) isomers were formed in small proportions but not isolated. The thermodynamically controlled, mutual interconversion of the stereoisomeric products was studied, as was the formation of nitronate salts and the regeneration of free nitroinositols. Upon immediate acidification, the nitronate obtained from 11 gave 11 and the neo-2 epimer (12) in a ratio of 2:3. The nitronate produced by 7 underwent rapid β-epimerization. The five isolated deoxynitroinositol monomethyl ethers were further characterized as tetra-acetates (7a, 9a, 11a, and 12a) and isopropylidene derivatives (7b, 8b, and 9b).     

Photochemical addition of 1,3-dioxolane and of 2-propanol to 1,2,4,6-tetra-O-acetyl-3-deoxy-α- and -β-D-erythro-hex-2-enopyranose

Photoirradiation of a solution of 1,2,4,6-tetra-O-acetyl-3-deoxy-β-D-erythro-hex-2-enopyranose (1) in 1:50 acetone-1,3-dioxolane with a high-pressure mercury-lamp, followed by chromatographic separation, gave 1,2,4,6-tetra-O-acetyl-3-deoxy-3-C-(1,3-dioxolan-2-yl)-β-D-glucopyranose (3) (44%) and-mannopyranose (4) (35%). Similar treatment of the α anomer (2) of 1 afforded 1,2,4,6-tetra-O-acetyl-3-deoxy-3-C-(1,3-dioxolan-2-yl)-α-D-glucopyranose (5) (38%), -mannopyranose (6) (31%), and -allopyranose (7) (21%).On the other hand, irradiation of 2 in 1:100 acetone-2-propanol gave 1,2,4,6-tetra-O-acetyl-3-deoxy-3-C-(1-hydroxy-1-methylethyl)-α-D-mannopyranose (8) (76%). Moreover, irradiation of 2 in 1:1 acetone-2-propanol yielded 1,4,6-tri-O-acetyl-3-deoxy-2,3-di-C-(1-hydroxy-1-methylethyl)-α-D-gluco- or -manno-pyranose 2,2¹,3¹-orthoacetate (10) (15%), in addition to 8 (44%).     

Location of a proton-donating group at the re-face of a β-d-galactosidase-bound,diastereotopic substrate

(Z)-3,7-Anhydro-1,2-dideoxy-2-deuterio-d-galacto-oct-2-enitol (1) was used as a diastereotopic probe, in order to elucidate the stereochemistry of protonation by β-d-galactosidase. Compound 1 can be converted by the enzyme into 1,2-dideoxy-2-deuterio-d-galacto-3-octulopyranose (2), which was submitted to periodate degradation. Propanoic acid derived from C-1, 2, and 3 of 2 has the (S) configuration, which proved the enzymic protonation of 1 to have taken place exclusively from the re-face.     

Conversion of allyl 2-acetamido-2-deoxy-β-d-glucopyranoside into 2-methyl-(3,4,6-tri-O-benzoyl-1,2-dideoxy-α-d- galactopyrano)-[2′,1′:4,5]-2-oxazoline

2-Methyl-(3,4,6-tri-O-benzoyl-1,2-dideoxy-α-d-galactopyrano)-[2′,1′:4,5]-2-oxazoline (7) was prepared from 1-propenyl 2-acetamido-3,4,6-tri-O-benzoyl-2- deoxy-β-d-galactopyranoside (6). The latter was prepared from allyl 2-acetamido-2-deoxy-β-d-glucopyranoside (1) through selective benzoylation at O-3 and O-6, conversion into the 4-p-bromobenzenesulfonate 4, inversion of configuration at C-4 to afford allyl 2-acetamido-3,4,6-tri-O-benzoyl-β-d-galactopyranoside (5), and subsequent isomerization with palladium-charcoal to give 6.     

Chemical constituents from Mentha canadensis

Phytochemical investigation on Mentha canadensis led to the isolation of two new compounds, 3,4-dihydro-3,6,7-trihydroxy-2(1H)-quinolinone (1), (E)-2-methoxy-2- oxethyl-3-(4-hydroxyphenyl) acrylate (2), along with nine known phenolic compounds, syringic acid (3), p-coumaric acid (4), esculetin (5), methyl rosmarinate (6), nepetoidin B (7), syringaresinol (8), methyl ester of caffeoyl glycollic acid (9), 2″,3″-diacetylmartynoside (10) and bracteanolide A (12). Additionally, cis-3-[2-[1-(3,4-dihydroxyphenyl)-1-hydroxymethyl]-1,3-benzodioxol-5-yl]-(E)-2-propenoic acid (11), which was isolated as a natural product for the first time. All these compounds were reported for the first time from this species, and their structures were elucidated by spectroscopic techniques. Compound 11 may be a useful chemotaxonomic marker for M. canadensis. The p-coumaric acid derivatives identified in the present investigation may have chemotaxonomic significance at the generic level.     

Microbial transformations of (−)-α- and (+)-β-thujone by fungi of Absidia species

The microbial transformations of (−)-α- and (+)-β-thujone (1a and 1b) in cultures of Absidia species: Absidia coerulea AM93, Absidia glauca AM254 and Absidia cylindrospora AM336 were studied. The biotransformations of (−)-α-thujone (1a), by these fungi strains, afforded mixtures of 4-hydroxy- and 7-hydroxy-α-thujone (2 and 3). Aforementioned fungi strains were also able to hydroxylate of (+)-β-thujone at C-7 position. Only A. glauca AM254 transformed 1b to 8-hydroxy-β-thujone (7) and (2S)-2-hydroxyneoisothujol (6). The (4R)-4-hydroxyisothujole (5) was identified as one of the major metabolite of (+)-β-thujone (1b) in culture of A. cylindrospora AM336. This strain was also able to introduce hydroxy group to C-4 position in 1b without reduction of carbonyl group at C-3. The absolute configuration of all chiral centers of new (4R)-4-hydroxyisothujol (5) and (2S)-2-hydroxyneoisothujol (6) were established taking into account the configuration of (+)-β-thujone (1b) and their spectral data.     

Synthesis and HMG-CoA reductase inhibition of 2-cyclopropyl-4-thiophenyl-quinoline mevalonolactones

A novel series of 2-cyclopropyl-4-thiophenyl quinoline-based mevalonolactones were synthesized from the substituted anilines by several reactions. Among them, (4R,6S)-6-[(E)-2-(2-cyclopropyl-6-fluoro-4-(4-fluoro-thiophenyl)-quinoline-3-yl)-ethenyl]-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-one (1d), (4R,6S)-6-[(E)-2-(2-cyclopropyl-6-fluoro-4-(3-methoxy-thiophenyl)-quinoline-3-yl)-ethenyl]-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-one (1f) and (4R,6S)-6-[(E)-2-(2-cyclopropyl-6-fluoro-4,7-di(3-methoxy-thiophenyl)-quinoline-3-yl)-ethenyl]-3,4,5,6-tetrahydro-4-hydroxy-2H-pyran-2-one (1q) showed potent HMG-CoA reductase inhibitory activity comparable with pitavastatin.