手性特窗酸类化合物的合成
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摘要
考察了一系列手性吡咯烷叔胺硫脲催化剂对4-氯代乙酰乙酸乙酯与亚胺的不对称Mannich/Cyclization串联反应的催化性能,合成了一系列具有潜在生物活性的手性特窗酸类衍生物,产率62%~92%,对映选择性68%~96%,产物结构经~1H NMR,~(13)C NMR,IR和HR-MS确证。并对反应条件进行了优化,对反应机理进行了推测。
The asymmetric Mannich/Cyclization cascade reaction of ethyl 4-chloro-3-oxobutanoate with imines catalyzed by a series of chiral pyrrolidine-based thiourea-tertiary amines were investigated. A series of chiral tetronic acids derivatives with potential biological activities were synthesized in 62% ~92% yields and 68% ~ 96% ee values. The structures were confirmed by ~1 H NMR,~(13) C NMR,IR and HR-MS. The reaction conditions were optimized and the catalytic mechanism was proposed.
The asymmetric Mannich/Cyclization cascade reaction of ethyl 4-chloro-3-oxobutanoate with imines catalyzed by a series of chiral pyrrolidine-based thiourea-tertiary amines were investigated. A series of chiral tetronic acids derivatives with potential biological activities were synthesized in 62% ~92% yields and 68% ~ 96% ee values. The structures were confirmed by ~1 H NMR,~(13) C NMR,IR and HR-MS. The reaction conditions were optimized and the catalytic mechanism was proposed.
引文
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[23]DAVID J,MORRIS A,MARTIN W,et al.Asymmetric organocatalysis of the addition of acetone to 2-nitrostyrene using N-diphenylphosphinyl-1,2-diphenylethane-1,2-diamine(PODPEN)[J].Tetrahedron Letters,2010,51(1):209-212.
[2]ATHANASELLIS G,MARKOPOULOU O I,MARKO-POULOS J.Tetramic and tetronic acids as scaffolds in bioinorganic and bioorganic chemistry[J].Bioinorg Chem and Appli,2010,11:1-11.
[3]UEDA C,TATEDA K,HORIKAWA M,et al.Anticlostridium difficile potential of tetramic acid derivatives from pseudomonas aeruginosa quorum-sensing autoinducers[J].Antimicrobial Agents Chemotherapy,2010,54(2):683-688.
[4]LOWERY C A,PARK J,GLOECKNER C,et al.Defining the mode of action of tetramic acid antibacterials derived from pseudomonas aeruginosa quorum sensing signals[J].J Am Chem Soc,2009,131(40):14473-14479.
[5]STEFAN P,SUN Y C,ZHANG R,et al.Design and structure-activity relationships of potent and selective inhibitors of undecaprenyl pyrophosphate synthase(UPPS):Tetramic,tetronic acids and dihydropyridin-2-ones[J].Bioorg Med Chem Let,2008,18(6):1840-1844.
[6]IWATA Y,MAEKAWARA N,TANINO K,et al.Tetramic acid antibiotics:Stereoselective synthesis of streptolic acid and tirandalydigin[J].Angew Chem Int Ed,2005,44(10):1532-1536.
[7]KUSUMI T,ICHIKAWA A,KAKISAWA H.The structures of quartromicins A,A2 and A3:Novel macrocyclic antiviral antibiotics possessing four tetronic acid moieties[J].J Am Chem Soc,1991,113(23):8947-8948.
[8]WITIAK D T,KOKRADY S S,PATEL S T,et al.Hypocholesterolemic and antiaggregatory properties of2-hydroxy-tetronic acid redox analogues and their relationship to clofibric acid[J].J Med Chem,1982,25(1):90-93.
[9]KHR G,HEINEMANN U.Effects of the tetronic acid derivatives AO33(losigamone)and AO78 on epileptiform activity and on stimulus-induced calcium concentration changes in rat hippocampal slices[J].Epilepsy Research,1990,7(1):49-58.
[10]GEBHARDTA C,BREUSTEDTA J M,LDNERB MN,et al.The antiepileptic drug losigamone decreases the persistent Na current in rat hippocampal neurons[J].Brain Research,2001,920:27-31.
[11]LUK K,READSHAW S A.Structural Studies of MM46115,a novel tetronic acid containing macrolide with antiviral and antibacterial activity isolated from actinomadura pelletieri[J].J Chem Soc,Perkin Trans,1991,1:1641-1644.
[12]BARBARA E R,FRANK P,RON D,et al.3-Alkanoyl-5-hydroxymethyl tetronic acid homologues and resistomycin:New inhibitors of HIV-1 protease[J].JAntibiotics,1994,47(2):136-142.
[13]DHEVALAPALLY B R,MAMILLAPALLI K.Direct catalytic asymmetric synthesis of highly functionalized tetronic acids/tetrahydro-isobenzofuran-1,5-diones via combination of cascade three-component reductive alkylations and Michael-aldol reactions[J].Org Biomol Chem,2010,8(12):2859-2867.
[14]JONATHAN J D,ANDREW C R.Asymmetric synthesis of tetronic acids by blaise reaction of protected optically active cyanohydrins[J].Tetrahedron Asymmetry,1996,7(3):663-666.
[15]AMARESH R R,LIN P.Regiospecific hydration ofγ-Hydroxy-α,β-acetylenic esters:A novel asymmetric synthesis of tetronic acids[J].Organic Letters,2006,8(10):2019-2021.
[16]RAINER S,CARSTEN J.Solution-phase and solidphase syntheses of enzyme inhibitor RK-682 and antibiotic agglomerins[J].J Org Chem,2005,70(15):6129-6132.
[17]JANA S,SIEGFRIED F,FRANZ E.Application of the blaise reaction:Stereoselective synthesis of(4R)-tert-butyl 3-amino-4-trimethylsilyloxy-2-alkenoates from(R)-cyanohydrins1[J].Tetrahedron Asymmetry,1998,9(5):805-815.
[18]LUO N H,SUN X,YAN M,et al.Asymmetric synthesis of O-alkylated tetronic acid derivatives via an organocatalytic Mannich reaction and subsequent intramolecular cyclization[J].Tetrahedron Asymmetry,2011,22(14):1536-1541.
[19]LUO N H,SUN X,YAN M,et al.Asymmetric synthesis of multicyclic spiro-1,3-indandiones via a cascade Michael/Michael reaction of curcumins and 2-arylidene-1,3-indandiones[J].Tetrahedron Asymmetry,2013,24(7):402-408.
[20]罗年华,郑大贵,谢国豪,等.新型手性吲哚酮类螺环化合物的合成与表征[J].化学试剂,2015,37(8):742-746.
[21]WENZEL A G,JACOBSEN E N.Asymmetric catalytic Mannich reactions catalyzed by urea derivatives:Enantioselective synthesis ofα-aryl-α-amino acids[J].J Am Chem Soc,2002,124:12964-12965.
[22]SHEN Z X,ZHANG Y Q,ZHANG Y W,et al.Enantioselective and diastereoselective Michael addition of Ketone/Aldehyde to trans-nitroolefins catalyzed by a novel chiral pyrrolidine-thiourea[J].Chirality,2007,19:307-312.
[23]DAVID J,MORRIS A,MARTIN W,et al.Asymmetric organocatalysis of the addition of acetone to 2-nitrostyrene using N-diphenylphosphinyl-1,2-diphenylethane-1,2-diamine(PODPEN)[J].Tetrahedron Letters,2010,51(1):209-212.