Z. Xiang et al.
The 1H and 13C NMR spectra were recorded with TMS as
internal standard using a Bruker AMX-400 MHz spectrom-
eter. Chemical shifts were expressed in parts per million and
coupling constants (J) in Hertz. IR spectra were measured
with a Nicolet Nexus FTIR 670 spectrophotometer. All the
Chen X, Liu BK, Kang H, Lin XF (2011) A tandem Aldol
condensation/dehydration co-catalyzed by acylase and N-hetero-
cyclic compounds in organic media. J Mol Catal B Enzym
68(1):71–76
Dhake KP, Tambade PJ, Singhal RS, Bhanage BM (2010) Promis-
cuous candida antarctica lipase B-catalyzed synthesis of b-amino
esters via aza-Michael addition of amines to acrylates. Tetrahe-
dron Lett 51(33):4455–4458
Feng XW, Li C, Wang N, Li K, Zhang WW, Wang Z, Yu XQ (2009)
Lipase-catalysed decarboxylative aldol reaction and decarboxy-
lative Knoevenagel reaction. Green Chem 11(12):1933–1936
Guan Z, Fu JP, He YH (2012) Biocatalytic promiscuity: lipase-
catalyzed asymmetric aldol reaction of heterocyclic ketones with
aldehydes. Tetrahedron Lett 53(37):4959–4961
He YH, Li HH, Chen YL, Xue Y, Yuan Y, Guan Z (2012)
Chymopapain-catalyzed direct asymmetric Aldol reaction. Adv
Synth Catal 354(4):712–719
1
known products were characterized by comparing the H
NMR data with those reported in the literature. The struc-
1
tures of new compounds were confirmed by IR, H NMR,
13C NMR, and HR-MS. Analytical HPLC was performed
using an Agilent 1100series with a reversed-phase Shim-
PackVP-ODS column(150 9 4.6 mm) and a UV detector
(250 nm).
General procedure for the enzymatic cascade
Horning EC, Field RE (1946) Preparation of 3-methyl-5-aryl-2-
cyclohexen-1-ones. J Am Chem Soc 68(3):384–387
Horning EC, Denekas MO, Field RE (1944) The preparation of
4-carbethoxy-3-methyl-5-alkyl-2-cyclohexen-1-ones and 3-methyl-
5-alkyl-2-cyclohexen-1-ones. J Org Chem 9(6):547–551
Kazlauskas RJ (2005) Enhancing catalytic promiscuity for biocatal-
ysis. Curr Opin Chem Biol 9(2):195–201
Khersonsky O, Tawfik DS (2010) Enzyme promiscuity: a mechanistic
and evolutionary perspective. Annu Rev Biophys Biomol
79:471–505
Kitazume T, Ikeya T, Murata K (1986) Synthesis of optically active
trifluorinated compounds: asymmetric Michael addition with
hydrolytic enzymes. J Chem Soc Chem Comm 17:1331–1333
Li K, He T, Li C, Feng XW, Wang N, Yu XQ (2009) Lipase-catalysed
direct Mannich reaction in water: utilization of biocatalytic
promiscuity for C–C bond formation in a ‘‘one-pot’’ synthesis.
Green Chem 11(6):777–779
Lin XF, Xu JM, Zhang F, Liu BK, Wu Q (2007) Promiscuous zinc-
dependent acylase-mediated carbon–carbon bond formation in
organic media. Chem Commun 20:2078–2080
for synthesis of 5-aryl-3-methylcyclohex-2-enones
A suspension of 1a–n (0.7 mmol), acetone (1.5 mL),
2.1-mmol imidazole and 400*mg D-aminoacylase in
10-mL octane was incubated at 50 °C and shaken for
48 h. After the indicated time, the enzyme was filtered
off to terminate the reaction and solvent was evaporated
under vacuum to dryness. The crude residue was puri-
fied by flash chromatography on silica gel using petro-
leum/ethyl
acetate
mixtures.
Product-containing
fractions were combined, concentrated, and dried to
give 5a–n.
Acknowledgments The authors gratefully acknowledge the finan-
cial support from National Natural Science Foundation of China (No.
21072172, 21272208).
Lin XF, Wu Q, Xu JM, Li X, Wang JL (2009) Promiscuous zinc-
dependent acylase-mediated one-pot synthesis of monosacchar-
ide-containing pyrimidine derivatives in organic medium. Adv
Synth Catal 351(11–12):1833–1841
Conflict of interest We declare that we have no competing finan-
cial interests.
Liu ZQ, Xiang ZW, Wu Q, Lin XF (2013) Unexpected three-
component domino synthesis of pyridin-2-ones catalyzed by
promiscuous acylase in non-aqueous solvent. Biochimie
95(7):1462–1465
References
Aleu J, Bustillo AJ, Hernandez-Galan R, Collado IG (2006)
Biocatalysis applied to the synthesis of agrochemicals. Cur
Org Chem 10(16):2037–2054
Authority EFS (2011) Scientific opinion on flavouring group evalu-
ation 212: a,b-unsaturated alicyclic ketones and precursors from
chemical subgroup 2.6 of FGE. 19. EFSA J 9(3):1923
Baas BJ, Zandvoort E, Geertsema EM, Poelarends GJ (2013) Recent
advances in the study of enzyme promiscuity in the tautomerase
superfamily. Chem Biol Chem 14(8):917–926
Busto E, Gotor-Fernandez V, Gotor V (2010) Hydrolases: catalyti-
cally promiscuous enzymes for non-conventional reactions in
organic synthesis. Chem Soc Rev 39(11):4504–4523
Cai JF, Guan Z, He YH (2011) The lipase-catalyzed asymmetric C–C
Michael addition. J Mol Catal B Enzym 68(3–4):240–244
Carlqvist P, Svedendahl M, Branneby C, Hult K, Brinck T, Berglund
P (2005) Exploring the active-site of a rationally redesigned
lipase for catalysis of Michael-type additions. Chem Biol Chem
6(2):331–336
Lou FW, Liu BK, Wu Q, Lv DS, Lin XF (2008) Candida antarctica
lipase B (CAL-B)-catalyzed carbon-sulfur bond addition and
controllable selectivity in organic media. Adv Synth Catal
350(13):1959–1962
´
Martınez R, Mendoza HM, Angeles E (1998) 5-Aryl-3-methyl-2-
cyclohexen-1-ones from 4-aryl-1, 4-dihydropyridines (Hantzsch
esters). Synth Commun 28(15):2813–2820
Mori K, Tamada S, Uchida M, Mizumachi N, Tachibana Y, Matsui M
(1978) Synthesis of optically active forms of seudenol, the
pheromone of douglas fir beetle. Tetrahedron 34(13):1901–1905
Nakayachi T, Yasumoto E, Nakano K, Morshed S, Hashimoto K,
Kikuchi H, Nishikawa H, Kawase M, Sakagami H (2004)
Structure-activity relationships of a,b-unsaturated ketones as
assessed by their cytotoxicity against oral tumor cells. Antican-
cer Res 24(2B):737–742
Plummer EL, Stewart TE, Byrne K, Pearce GT, Silverstein RM
(1976) Determination of the enantiomeric composition of several
insect pheromone alcohols. J Chem Ecol 2(3):307–331
Pollard DJ, Woodley JM (2007) Biocatalysis for pharmaceutical
intermediates: the future is now. Trends Biotechnol
25(2):66–73
Chai SJ, Lai YF, Xu JC, Zheng H, Zhu Q, Zhang P (2011) One-pot
synthesis of spirooxindole derivatives catalyzed by lipase in the
presence of water. Adv Synth Catal 353(2–3):371–375
123