Hyun-Joon Ha, Won Koo Lee and Jungchan Park                                           

 

 

 

Ceramide is an apoptosis-including signaling molecule in the sphinolipid metabolism which emerges as a potential target for anticancer therapy. Natural ceramide in solution has a uniquely folded butterfly conformer with strong internal hydrogen bonding between amide and two alcohols at C1 and C3 and with hydrophobic interaction between two long alkyl chain of sphingosine backbone and fatty acid. Its heterocyclic analogs as 3-alkanoyl or benzoyl-4-(1-hydroxyhexadec-2-enyl)-oxazolidin-2-ones were designed by binding of primary alcohol and amide in sphingosine backbone as a carbamate. Those compounds without free primary alcohol have advantages not to perturb the ceramide metabolism most of which involved in the primary alcohol of sphingosing backbone. This structurally constrained analog of ceramide may have better activity compared with the natural ceramide without pre-organization of substrate, if necessary. They were synthesized by addition of acyl halide to the common ring, 4-(1-t-butyldimethylsillyloxyhexadec-2enyl)-oxazolidine-2-one, which was elaborated from chiral aziridine-2-carboxylate including stereoselective reduction and ring opening reactions. All compounds were tested as antileukemic drugs against human leukemia HL-60 cells. Many of them including propionyl, cyclopentanoyl and p-nitrobenzoyl-4-(1-hydroxyhexadec-2-enyl)oxazolidin-2-ones showed better antileukemic activities than natural C2-ceramide with good correlation between cell death and DNA fragmentation.

 

 

 

59.jpg

 

List of Articles
번호 제목 글쓴이 날짜 조회 수
88 88. Atom Economical Synthesis of Oxindoles by Metal-Catalyzed Intramolecular C-C Bond Formation under Solvent-Free and Aerobic Conditions, Green Chem., 2015, 17, 3306–3309 imagefile aziridine 2016-03-18 898
87 87. N-Methylative aziridine ring opening: Asymmetric synthesis of hygroline, pseudohygroline, and hygrine, Tetrahedron Letters 56 (2015) 856–858 imagefile aziridine 2016-03-18 884
86 86. One-pot Solvent-Free Reductive Amination with a Solid Ammonium Carbamate Salt from CO2 and Amine, RSC Adv., 2014, 4, 46203–46207 imagefile aziridine 2016-03-18 831
85 85. Asymmetric Synthesis of Fluoroamines from Chiral Aziridines, Bull. Korean Chem. Soc. 2014, Vol. 35, No. 3 file aziridine 2016-03-18 847
84 84. Synthesis and Biological Activities of Tyroscherin Analogs, Bull. Korean Chem. Soc. 2013, Vol. 34, No. 6 file aziridine 2016-03-18 789
83 83. Highly Stereoselective Directed Reactions and an Efficient Synthesis of Azafuranoses from a Chiral Aziridine, Org Biomol Chem. 2013 Jun 14;11(22):3629-34 imagefile aziridine 2016-03-18 736
82 82. CAL-B catalyzed desymmetrization of 3-alkylglutarate: "olefin effect" and asymmetric synthesis of pregabalin, Org. Biomol. Chem., 2013, 11, 3635 imagefile aziridine 2013-08-27 1892
81 81. Highly stereoselective directed reactions and an efficient synthesis of azafuranoses from a chiral aziridine, Org. Biomol. Chem., 2013, 11, 3629 imagefile aziridine 2013-08-27 1908
80 80. Stereoselective synthesis of (-)-8-epi-swainsonine starting with a chiral aziridine, Tetrahedron Lett., 2013, 54, 553 imagefile aziridine 2013-08-27 1807
79 79. Solid-state and solvent-free synthesis of azines, pyrazoles, and pyridazinones using solid hydrazine, Tetrahedron Lett., 2013, 54, 1384 imagefile aziridine 2013-08-27 1810
78 78. Chemoselective reduction of olefin by mixed "Pd" catalyst, Bulletin of the Korean Chemical Society (2012), 33(9), 2853-2854. imagefile aziridine 2013-05-30 1839
77 77. Highly improved copper-mediated Michael addition of ethyl bromodifluoroacetate in the presence of protic additive, Synthesis (2012), 44(20), 3165-3170. imagefile aziridine 2013-05-30 1472
76 76. The sphingosine-1-phosphate derivative NHOBTD inhibits angiogenesis both in vitro and in vivo, Biochemical and biophysical research communications (2011), 413(2), 189-93. file aziridine 2013-05-30 1428
75 75. Synthesis of 2,5-Disubstituted 6-Azaindoles from Substituted Aziridines via Intramolecular Cyclization, ORGANIC LETTERS, 2012, Vol. 14, No. 12, 3120–3122. imagefile aziridine 2012-06-11 1987
74 74. Alkylative Ring Opening of N-Methylaziridinium Ions and a Formal Synthesis of Tyroscherin, Org. Lett., 2012, Vol. 14, No. 2, 429–431 imagefile aziridine 2012-06-11 1957
73 73. Asymmetric synthesis of 1-deoxyazasugars from chiral aziridines, Org. Biomol. Chem., 2011, 9, 1372 imagefile aziridine 2012-01-27 2704
72 72. Chiral aziridine-2-carboxylates: versatile precursors for functionalized tetrahydroisoquinoline (THIQ) containing heterocycles, Tetrahedron 68 (2012) 883-893 imagefile aziridine 2012-01-27 2484
71 71. 3,4-Disubstituted oxazolidin-2-ones as constrained ceramide analogs with anticancer activities. Bioorganic & Medicinal Chemistry 19 (2011) 6174–6181 imagefile aziridine 2012-01-27 2663
70 70. N-Methylative aziridine ring opening and asymmetric synthesis of MeBmt. Tetrahedron Letters 52 (2011) 5918–5920 imagefile aziridine 2012-01-27 2667
69 69. Regiochemical Pathway in the Ring Opening of 2-Acylaziridines. Bull. Korean Chem. Soc. 2011, Vol. 32, No. 8 2879 imagefile aziridine 2012-01-27 2767
68 68. Synthesis of 1,2,5-and 1,2,3,5-substituted pyrroles from substituted aziridines via Ag(I)-catalyzed intramolecular cyclization , Tetrahedron 67 (2011) 3553-3556. imagefile aziridine 2011-05-06 3365
67 67. Aminostyrylbenzofuran derivatives as potent inhibitors for Aβ fibril formation-BMCL, 2008, 18, 5591-5593 imagefile aziridine 2010-09-27 4176
66 66. An efficient synthesis of enantiomerically pure aromatic-fused N-containing heterocycles from common chiral aziridines - Tetrahedron, 2010, 66, 8108-8114 imagefile aziridine 2010-09-08 4166
65 65. A formal synthesis of (-)-swainsonine from a chiral aziridine - Tetrahedron Lett. 2010, 51, 3284 imagefile aziridine 2010-05-29 4449
64 64. Conjugate addition of amines to chiral 3-aziridin-2-yl-acrylates - Tetrahedron Lett. 2010, 2181 imagefile aziridine 2010-05-29 4504
63 63. Synthesis of substituted imidazolidin-2-ones as aminoacyl-tRNA synthase inhibitors - Bull.Kor.Chem.Soc. 2010, 611 imagefile aziridine 2010-05-29 4267
62 62. Molecular docking study of aminoacyl-tRNA synthetases with ligand molecules from four different scaffolds - Bull.Kor.Chem.Soc 2010, 606 imagefile aziridine 2010-05-29 3836
61 61. Molecular basis for the stereoselective ammoniolysis of N-alkyl aziridine-2-carboxylates catalyzed by Candida antarctica lipase B - ChemBioChem 2009, 10, 2213 imagefile aziridine 2010-05-29 4099
60 60. Synthesis of D-erythro-sphingosine from D-ribo-phytosphingoshine - Bull. Kor. Chem. Soc. 2009, 535 imagefile aziridine 2010-05-29 3889
» 59. [Synthetic ceramide analogs for anticancer agents] in Glycolipids New Research, Nova Science Pub. New York, 2008, 145- 156 imagefile aziridine 2010-05-29 4196


XE Login