964
Chem. Pharm. Bull.
Vol. 64, No. 7 (2016)
Chartꢀ 6.ꢀ RegioselectivityꢀImprovementꢀofꢀtheꢀDeacetylationꢀofꢀ1fꢀCatalyzedꢀbyꢀC. antarcticaꢀLipaseꢀB,ꢀandꢀItsꢀApplicationꢀtoꢀtheꢀSynthesisꢀofꢀSeli-
none (1c)
tography to afford ( )-1hꢀ asꢀ aꢀ yellowꢀ solidꢀ (395.0ꢀmg,ꢀ 95%).ꢀ stirredꢀ forꢀ 28ꢀhꢀ atꢀ 22°C.ꢀ Theꢀ mixtureꢀ wasꢀ filteredꢀ toꢀ removeꢀ
1
mpꢀ 98.6–99.5°C.ꢀ H-NMRꢀ (400ꢀMHz,ꢀ CDCl3) δ:ꢀ 2.30ꢀ (3H,ꢀ insolubleꢀmaterialsꢀwithꢀaꢀpadꢀofꢀCelite.ꢀTheꢀprecipitatesꢀwereꢀ
s), 2.36 (3H, s), 2.71 (1H, dd, J=2.9,ꢀ 16.8ꢀHz),ꢀ 2.98ꢀ (1H,ꢀ dd,ꢀ washedꢀwithꢀAcOEt.ꢀTheꢀcombinedꢀfiltrateꢀandꢀwashingsꢀwereꢀ
J=13.3,ꢀ 16.8ꢀHz),ꢀ 3.81ꢀ (3H,ꢀ s),ꢀ 5.45ꢀ (1H,ꢀ dd,ꢀ J=2.9,ꢀ 13.3ꢀHz),ꢀ concentrated in vacuo.ꢀ Theꢀ residueꢀ wasꢀ purifiedꢀ byꢀ silicaꢀ gelꢀ
6.27 (1H, d, J=2.7ꢀHz),ꢀ 6.40ꢀ (1H,ꢀ d,ꢀ J=2.7ꢀHz),ꢀ 7.13ꢀ (2H,ꢀ columnꢀ chromatographyꢀ (40ꢀg,ꢀ hexane–AcOEt=1ꢀ:ꢀ1)ꢀ toꢀ affordꢀ
d, J=8.4ꢀHz),ꢀ 7.44ꢀ (2H,ꢀ d,ꢀ J=8.4ꢀHz).ꢀ 13C-NMRꢀ (125ꢀMHz,ꢀ ( )-1kꢀ asꢀ aꢀ colorlessꢀ solidꢀ (1.45ꢀg,ꢀ 82%).ꢀ mpꢀ 113.9–114.8°C.ꢀ
CDCl3) δ:ꢀ21.1,ꢀ21.1,ꢀ45.0,ꢀ55.8,ꢀ79.0,ꢀ99.5,ꢀ104.8,ꢀ107.9,ꢀ122.1,ꢀ 1H-NMRꢀ(400ꢀMHz,ꢀCDCl3) δ:ꢀ2.30ꢀ(3H,ꢀs),ꢀ2.39ꢀ(3H,ꢀs),ꢀ2.70ꢀ
127.4, 136.0, 150.9, 151.9, 164.1, 165.5, 169.3, 169.5, 188.6. (1H, dd, J=2.6,ꢀ 16.7ꢀHz),ꢀ 3.00ꢀ (1H,ꢀ dd,ꢀ J=13.7,ꢀ 16.7ꢀHz),ꢀ 5.32ꢀ
IRꢀ cm−1:ꢀ 2977,ꢀ 1772,ꢀ 1685,ꢀ 1616,ꢀ 1193,ꢀ 1153.ꢀ HR-MSꢀ (ESI+) (1H, dd, J=2.6,ꢀ 13.7ꢀHz),ꢀ 6.52ꢀ (1H,ꢀ d,ꢀ J=2.4ꢀHz),ꢀ 6.75ꢀ (1H,ꢀ
Calcd for C20H18NaO7ꢀ[M+Na]+ꢀ393.0950.ꢀFoundꢀ393.0941.ꢀItsꢀ d, J=2.4ꢀHz),ꢀ 6.82ꢀ (2H,ꢀ d,ꢀ J=8.7ꢀHz),ꢀ 7.25ꢀ (2H,ꢀ d,ꢀ J=8.7ꢀHz).ꢀ
NMRꢀspectrumꢀwasꢀidenticalꢀwithꢀthatꢀreportedꢀpreviously.10) 13C-NMRꢀ (125ꢀMHz,ꢀ CDCl3) δ:ꢀ 21.1,ꢀ 21.2,ꢀ 44.8,ꢀ 79.3,ꢀ 109.3,ꢀ
Alternatively, to a solution of 1g (200.1mg, 0.56mmol) in 110.4, 115.6, 128.0, 129.7, 151.1, 155.9, 156.4, 156.6, 163.5,
DMFꢀ (2ꢀmL)ꢀ wereꢀ addedꢀ methylꢀ iodideꢀ (42ꢀµL, 0.67mmol) 168.3,ꢀ 169.9,ꢀ 190.0.ꢀ IRꢀ cm−1:ꢀ 3382,ꢀ 1770,ꢀ 1683,ꢀ 1508,ꢀ 1373,ꢀ
andꢀ potassiumꢀ carbonateꢀ (77.4ꢀmg,ꢀ 0.56ꢀmmol)ꢀ andꢀ theꢀ mix- 1157,ꢀ 1016.ꢀ HR-MSꢀ (ESI+) Calcd for C19H16NaO7ꢀ [M+Na]+
tureꢀ wasꢀ stirredꢀ forꢀ 17ꢀhꢀ atꢀ roomꢀ temperature.ꢀ Theꢀ mixtureꢀ 379.0794.ꢀ Foundꢀ 379.0790.ꢀ Itsꢀ NMRꢀ spectrumꢀ wasꢀ identicalꢀ
wasꢀ quenchedꢀ withꢀ saturatedꢀ aqueousꢀ NH4Cl (2mL), and the withꢀthatꢀreportedꢀpreviously.15)
organicꢀ materialsꢀ wereꢀ extractedꢀ withꢀ AcOEt.ꢀ Theꢀ combinedꢀ
( )-5,7-Dihydroxy-4′-(3-methyl-but-2-enyloxy)flavan-4-
organicꢀlayerꢀwasꢀwashedꢀwithꢀbrine,ꢀdriedꢀoverꢀNa2SO4, and one (Selinone), 1c To a solution of 1k (839.8mg, 2.38mmol),
concentrated in vacuo.ꢀ Theꢀ residueꢀ wasꢀ purifiedꢀ byꢀ silicaꢀ gelꢀ triphenylphosphineꢀ (749.1ꢀmg,ꢀ 2.87ꢀmmol),ꢀ andꢀ 3-methyl-2-
columnꢀchromatographyꢀ(5.0ꢀg,ꢀhexane–AcOEt=3ꢀ:ꢀ1)ꢀtoꢀaffordꢀ buten-1-olꢀ (350ꢀµL,ꢀ 3.50ꢀmmol)ꢀ inꢀ THFꢀ (20ꢀmL)ꢀ wasꢀ addedꢀ
( )-1hꢀasꢀaꢀyellowꢀsolidꢀ(197.4ꢀmg,ꢀ95%).
dropwiseꢀaꢀsolutionꢀofꢀdiisopropylꢀazodicarboxylateꢀinꢀtolueneꢀ
( )-5,4′-Dihydroxy-7-methoxyflavan-4-one (Sakuranetin), (1.96ꢀmL,ꢀ3.85ꢀmmol)ꢀatꢀ0°C.ꢀTheꢀreactionꢀmixtureꢀwasꢀwarmꢀ
1b To a solution of 1h (50.0mg, 0.14mmol) in metha- to room temperature and stirred for 24h. After removal of the
nolꢀ (2ꢀmL)ꢀ wasꢀ addedꢀ 28%ꢀ NaOMeꢀ inꢀ methanolꢀ (50ꢀµL, solvent in vacuo,ꢀhighlyꢀpolarꢀsubstanceꢀwasꢀremovedꢀbyꢀshortꢀ
0.28ꢀmmol)ꢀ andꢀ theꢀ mixtureꢀ wasꢀ stirredꢀ forꢀ 2ꢀhꢀ atꢀ roomꢀ tem- silica gel column chromatography to afford ( )-1lꢀasꢀaꢀyellowꢀ
perature.ꢀ Theꢀ mixtureꢀ wasꢀ quenchedꢀ withꢀ saturatedꢀ aque- solidꢀ(880.0ꢀmg).ꢀThisꢀwasꢀemployedꢀforꢀtheꢀnextꢀstepꢀwithoutꢀ
ous NH4Clꢀ (5ꢀmL),ꢀ andꢀ theꢀ organicꢀ materialsꢀ wereꢀ extractedꢀ furtherꢀpurification.
withꢀ AcOEt.ꢀ Theꢀ combinedꢀ organicꢀ layerꢀ wasꢀ washedꢀ withꢀ
To a solution of 1l (880.0mg, 2.38mmol) in methanol
brine, dried over Na2SO4, and concentrated in vacuo. The (30ꢀmL)ꢀ wasꢀ addedꢀ 28%ꢀ NaOMeꢀ inꢀ methanolꢀ (440ꢀµL,
residueꢀ wasꢀ purifiedꢀ byꢀ silicaꢀ gelꢀ columnꢀ chromatographyꢀ 5.76ꢀmmol)ꢀ andꢀ theꢀ mixtureꢀ wasꢀ stirredꢀ forꢀ 2ꢀhꢀ atꢀ roomꢀ tem-
(1.0ꢀg,ꢀ hexane–AcOEt=3ꢀ:ꢀ1)ꢀ toꢀ affordꢀ ( )-1b as a colorless perature.ꢀ Theꢀ mixtureꢀ wasꢀ quenchedꢀ withꢀ saturatedꢀ aqueousꢀ
solidꢀ (37.2ꢀmg,ꢀ 96%).ꢀ mpꢀ 135.2–136.1°C.ꢀ 1H-NMRꢀ (400ꢀMHz,ꢀ NH4Clꢀ(20ꢀmL),ꢀandꢀtheꢀorganicꢀmaterialsꢀwereꢀextractedꢀwithꢀ
CDCl3) δ:ꢀ2.76ꢀ(1H,ꢀdd,ꢀJ=2.9,ꢀ17.0ꢀHz),ꢀ3.07ꢀ(1H,ꢀdd,ꢀJ=13.1, AcOEt.ꢀ Theꢀ combinedꢀ organicꢀ layerꢀ wasꢀ washedꢀ withꢀ brine,ꢀ
17.0ꢀHz),ꢀ3.79ꢀ(3H,ꢀs),ꢀ5.35ꢀ(1H,ꢀdd,ꢀJ=2.9,ꢀ13.1ꢀHz),ꢀ6.02ꢀ(1H,ꢀ dried over Na2SO4, and concentrated in vacuo. The residue
d, J=2.4ꢀHz),ꢀ 6.05ꢀ (1H,ꢀ d,ꢀ J=2.4ꢀHz),ꢀ 6.86ꢀ (2H,ꢀ d,ꢀ J=8.6ꢀHz),ꢀ wasꢀpurifiedꢀbyꢀsilicaꢀgelꢀcolumnꢀchromatographyꢀ(20ꢀg,ꢀhex-
7.30 (2H, d, J=8.6ꢀHz).ꢀ 13C-NMRꢀ (125ꢀMHz,ꢀ CDCl3) δ:ꢀ 43.1,ꢀ ane–AcOEt=3ꢀ:ꢀ1)ꢀtoꢀaffordꢀ( )-1cꢀasꢀaꢀyellowꢀsolidꢀ(600.3ꢀmg,ꢀ
1
55.8, 79.0, 94.2, 95.0, 103.1, 115.6, 127.8, 130.5, 156.1, 162.9, 69%ꢀ overꢀ 2ꢀ steps).ꢀ mpꢀ 139.8–140.5°C.ꢀ H-NMRꢀ (400ꢀMHz,ꢀ
164.1,ꢀ 168.0,ꢀ 196.0.ꢀ IRꢀ cm−1:ꢀ 3326,ꢀ 1648,ꢀ 1515,ꢀ 1454,ꢀ 1205,ꢀ CDCl3) δ:ꢀ 1.73ꢀ (3H,ꢀ s),ꢀ 1.78ꢀ (3H,ꢀ s),ꢀ 2.76ꢀ (1H,ꢀ dd,ꢀ J=3.1,
1149,ꢀ 1029.ꢀ HR-MSꢀ (ESI+) Calcd for C16H14NaO5ꢀ [M+Na]+ 17.0ꢀHz),ꢀ3.08ꢀ(1H,ꢀdd,ꢀJ=13.1,ꢀ17.0ꢀHz),ꢀ4.51ꢀ(2H,ꢀd,ꢀJ=6.6ꢀHz),ꢀ
309.0739.ꢀ Foundꢀ 309.0754.ꢀ Itsꢀ NMRꢀ spectrumꢀ wasꢀ identicalꢀ 5.33 (1H, dd, J=3.1,ꢀ 13.1ꢀHz),ꢀ 5.42ꢀ (1H,ꢀ m),ꢀ 5.96ꢀ (1H,ꢀ d,ꢀ
withꢀthatꢀreportedꢀpreviously.10)
J=2.4ꢀHz),ꢀ5.98ꢀ(1H,ꢀd,ꢀJ=2.4ꢀHz),ꢀ6.95ꢀ(2H,ꢀd,ꢀJ=8.8ꢀHz),ꢀ7.34ꢀ
( )-5,7-Diacetoxy-4′-hydroxyflavan-4-one (5,7-Diacetyl- (2H, d, J=8.8ꢀHz).ꢀ13C-NMRꢀ(125ꢀMHz,ꢀCDCl3) δ:ꢀ18.2,ꢀ25.8,ꢀ
naringenin), 1k To a solution of 1f (1.97g, 4.94mmol) in a 43.1, 64.9, 79.0, 95.5, 96.7, 103.1, 114.9, 119.3, 127.7, 130.1,
mixtureꢀ ofꢀ 2-propanolꢀ (10ꢀmL)ꢀ andꢀ THFꢀ (20ꢀmL),ꢀ whichꢀ wasꢀ 138.6,ꢀ 159.3,ꢀ 163.2,ꢀ 164.3,ꢀ 164.9,ꢀ 196.1.ꢀ IRꢀ cm−1:ꢀ 3282,ꢀ 1610,ꢀ
pre-driedꢀ overꢀ anhydrousꢀ Na2SO4 at room temperature over- 1558,ꢀ 1540,ꢀ 1488,ꢀ 1471,ꢀ 1361,ꢀ 1087,ꢀ 1012.ꢀ HR-MSꢀ (ESI+)
night,ꢀwasꢀaddedꢀanꢀimmobilizedꢀformꢀofꢀC. antarctica lipase Calcd for C20H20NaO5ꢀ[M+Na]+ꢀ363.1208.ꢀFoundꢀ363.1203.ꢀItsꢀ
Bꢀ (Novozymes,ꢀ Novozymꢀ 435,ꢀ 192ꢀmg).ꢀ Theꢀ mixtureꢀ wasꢀ NMRꢀspectrumꢀwasꢀidenticalꢀwithꢀthatꢀreportedꢀpreviously.15)