- A practical and scalable synthesis of KRN7000 using glycosyl iodide as the glycosyl donor
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KRN7000 is particularly useful because it is a powerful and specific CD1d agonist and has prompted intense interest in the context of immunology in the past 25 years. Its limited commercial availability and high price has led to the publication of many different syntheses. However, almost all of them focused on the methodology development rather than a scalable synthesis. Herein, we have described a practical and scalable procedure for the synthesis of KRN7000 basing on the glycosyl iodide method. This procedure involves total of eight steps to obtain the highly pure product KNR7000 on gram scale from the commercially available starting materials (d-galactose and the phytosphingosine) with only three column chromatographic purifications.
- Zhang, Yang,Guo, Jia,Xu, Xiaoyan,Gao, Qi,Liu, Xianglai,Ding, Ning
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Read Online
- New synthetic thiocolchicine derivatives as low-toxic anticancer agents
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New thiocolchicine derivatives (1-8) were designed as less toxic anticancer agents possessing the powerful anticancer activity of colchicine. The synthesis and biological evaluation of these compounds were described. As a preliminary result of biological in vitro investigation, compounds 1, 6, and 7 showed lower toxicities than that of colchicine in combination with potent anticancer activities.
- Lee, Sun-Hee,Park, Sun-Kyoung,Kim, Jeong-Mi,Kim, Myung-Hwa,Kim, Kwang-Hee,Chun, Kwang-Woo,Cho, Kyung-Hea,Youn, Ji-Youn,Namgoong, Sung Keon
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Read Online
- 4'-HALOGEN CONTAINING NUCLEOTIDE AND NUCLEOSIDE THERAPEUTIC COMPOSITIONS AND USES RELATED THERETO
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Disclosed are halogen containing nucleotide and nucleoside therapeutic compositions and uses related thereto. In certain embodiments, the disclosure relates to the treatment or prophylaxis of viral infections. Such viral infections can include tongaviridae, bunyaviridae, arenaviridae, coronaviridae, flaviviridae, picornaviridae, Eastern, Western, and Venezuelan Equine Encephalitis (EEE, WEE and VEE, respectively), Chikungunya fever (CHIK), Ebola, Influenza, RSV, and Zika virus infections.
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Page/Page column 314-315
(2021/07/10)
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- 4'-HALOGEN CONTAINING NUCLEOTIDE AND NUCLEOSIDE THERAPEUTIC COMPOSITIONS AND USES RELATED THERETO
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Disclosed are halogen containing nucleotide and nucleoside therapeutic compositions and uses related thereto. In certain embodiments, the disclosure relates to the treatment or prophylaxis of viral infections. Such viral infections can include tongaviridae, bunyaviridae, arenaviridae, coronaviridae, flaviviridae, picornaviridae, Eastern, Western, and Venezuelan Equine Encephalitis (EEE, WEE and VEE, respectively), Chikungunya fever (CHIK), Ebola, Influenza, RSV, and Zika virus infections.
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(2019/10/01)
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- NUCLEOTIDE AND NUCLEOSIDE THERAPEUTIC COMPOSITIONS AND USES RELATED THERETO
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This disclosure relates to nucleotide and nucleoside therapeutic compositions and uses in treating infectious diseases, viral infections, and cancer, where the base of the nucleotide or nucleoside contains at least one thiol, thione or thioether.
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Page/Page column 72
(2017/07/14)
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- NUCLEOTIDE AND NUCLEOSIDE THERAPEUTIC COMPOSITIONS AND USES RELATED THERETO
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This disclosure relates to nucleotide and nucleoside therapeutic compositions and uses in treating infectious diseases, viral infections, and cancer, where the base of the nucleotide or nucleoside contains at least one thiol, thione or thioether.
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Page/Page column 150
(2017/09/27)
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- ALKYNE CONTAINING NUCLEOTIDE AND NUCLEOSIDE THERAPEUTIC COMPOSITIONS AND USES RELATED THERETO
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This disclosure relates to nucleotide and nucleoside therapeutic compositions and uses in treating infectious diseases, viral infections, and cancer, where the base of the nucleotide or nucleoside contains at least one thiol, thione or thioether.
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Page/Page column 314
(2017/12/09)
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- NUCLEOTIDE AND NUCLEOSIDE THERAPEUTICS COMPOSITIONS AND USES RELATED THERETO
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This disclosure relates to nucleotide and nucleoside therapeutic compositions and uses in treating infectious diseases, viral infections, and cancer, where the base of the nucleotide or nucleoside contains at least one thiol, thione or thioether.
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Page/Page column 274
(2016/09/26)
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- NOVEL PHYTOSPHINGOSINE-1-PHOSPHATE DERIVATIVE, PREPARATION METHOD THEREFOR, AND COMPOSITION FOR PREVENTING AND TREATING HAIR LOSS OR FOR GROWING HAIR COMPRISING SAME
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The present invention provides: O-cyclic phytospingosine-1-phosphate (0-C-P1P), N-cyclic phytospingosine-1-phosphate (N-C-P1P), a pharmaceutically acceptable salt thereof, or a solvate thereof; a preparation method therefor; a cosmetic composition comprising the same for preventing hair loss or for growing hair; and a pharmaceutical composition for preventing and treating hair loss or for growing hair.
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Paragraph 0062; 0091
(2016/03/22)
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- NUCLEOTIDE AND NUCLEOSIDE COMPOSITIONS AND USES RELATED THERETO
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This disclosure relates to nucleotide and nucleoside therapeutic compositions and uses in treating infectious diseases, viral infections, and cancer, where the base of the nucleotide or nucleoside contains at least one thiol, thione or thioether.
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Page/Page column 225
(2015/03/28)
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- Protein and peptide-free synthetic vaccines against streptococcus pneumoniae type 3
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The present invention provides a protein- and peptide-free conjugate comprising a synthetic carbohydrate and a carrier molecule, wherein the synthetic carbohydrate is a Streptococcus pneumoniae type 3 capsular polysaccharide related carbohydrate and the carrier molecule is a glycosphingolipid. Said conjugate and pharmaceutical composition thereof are useful for immunization against diseases associated with Streptococcus pneumoniae, and more specifically against diseases associated with Streptococcus pneumoniae type 3.
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- PROTEIN AND PEPTIDE-FREE SYNTHETIC VACCINES AGAINST STREPTOCOCCUS PNEUMONIAE TYPE 3
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The present invention provides a protein- and peptide-free conjugate comprising a synthetic carbohydrate and a carrier molecule, wherein the synthetic carbohydrate is a Streptococcus pneumoniae type 3 capsular polysaccharide related carbohydrate and the carrier molecule is a glycosphingolipid. Said conjugate and pharmaceutical composition thereof are useful for immunization against diseases associated with Streptococcus pneumoniae, and more specifically against diseases associated with Streptococcus pneumoniae type 3.
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- POLYSACCHARIDE ANTIGEN-GLYCOLIPID CONJUGATE VACCINES
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The present invention relates to the field of synthesizing and biologically evaluating of a novel class of carbohydrate-based vaccines. The new vaccines consist of a multi-modular structure which allows applying the vaccine to a whole variety of pathogenes. This method allows preparing vaccines against all pathogens expressing immunogenic carbohydrate antigens. As conjugation of antigenic carbohydrates to proteins is not required the conjugate vaccine is particularly heat stable. No refrigeration is required, a major drawback of protein-based vaccines.
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- CARBOHYDRATE-GLYCOLIPID CONJUGATE VACCINES
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The present invention relates to the field of synthesizing and biologically evaluating of a novel class of carbohydrate-based vaccines. The new vaccines consist of a multi-modular structure which allows applying the vaccine to a whole variety of pathogenes. This method allows preparing vaccines against all pathogens expressing immunogenic carbohydrate antigens. As conjugation of antigenic carbohydrates to proteins is not required the conjugate vaccine is particularly heat stable. No refrigeration is required, a major drawback of protein-based vaccines.
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- NUCLEOTIDE AND NUCLEOSIDE THERAPEUTIC COMPOSITIONS AND USES RELATED THERETO
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This disclosure relates to nucleotide and nucleoside therapeutic compositions and uses related thereto. In certain embodiments, the disclosure relates to halogenated nucleosides optionally conjugated to a phosphorus oxide or pharmaceutically acceptable salts thereof. In certain embodiments, the disclosure relates to conjugate compounds or pharmaceutically acceptable salts thereof comprising an amino acid ester or a sphingolipid or derivative linked by a phosphorus oxide to a nucleotide or nucleoside. In certain embodiments, the disclosure contemplates pharmaceutical compositions comprising these compounds for uses in treating infectious diseases, viral infections, and cancer.
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Page/Page column 200
(2014/08/20)
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- A stereocontrolled route to d-ribo-phytosphingosine and sphinganine from an achiral secondary homoallylic alcohol using Sharpless kinetic resolution
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A facile and efficient enantioselective route for the synthesis of d-ribo-phytosphingosine (1a) and sphinganine (1b) has been developed employing commercially available and cheap starting material trans-cinnamaldehyde 2. The synthetic strategy features the Sharpless kinetic resolution, regioselective epoxide opening and Wittig olefination as the key steps.
- Devi, Thongam Joymati,Saikia, Bishwajit,Barua, Nabin C.
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p. 3817 - 3822
(2013/06/27)
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- Regioselective inversion of the hydroxyl group in d-ribo-phytosphingosine via a cyclic sulfate and bis-sulfonate intermediate
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The selective synthesis of d-xylo-and d-lyxo-phytosphingosines from commercially available d-ribo-phytosphingosine is described. Thermolysis of the N-carbonyl protected cyclic sulfate led to an inversion of configuration of the proximal hydroxyl group to
- Lee, Yun Mi,Baek, Dong Jae,Lee, Seokwoo,Kim, Deukjoon,Kim, Sanghee
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experimental part
p. 408 - 416
(2011/03/20)
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- Synthesis of a versatile building block for the preparation of 6-N-derivatized α-galactosyl ceramides: Rapid access to biologically active glycolipids
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A concise route to the 6-azido-6-deoxy-α-galactosyl-phytosphingosine derivative 9 is reported. Orthogonal protection of the two amino groups allows elaboration of 9 into a range of 6-N-derivatized α-galactosyl ceramides by late-stage introduction of the a
- Jervis, Peter J.,Cox, Liam R.,Besra, Gurdyal S.
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supporting information; experimental part
p. 320 - 323
(2011/03/20)
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- A common and stereoselective strategy for the synthesis of N,O,O,O-tetra-acetyl d-ribo-(2S,3S,4R)-phytosphingosine and 2-epi-jaspine B
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A common and stereoselective strategy for the synthesis of N,O,O,O-tetra-acetyl d-ribo-(2S,3S,4R)-phytosphingosine and 2-epi-jaspine B was achieved by using Grignard addition on N-benzyl sugar lactamine and Wittig olefination as key steps.
- Srinivas Rao,Venkateswara Rao
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scheme or table
p. 4861 - 4864
(2011/10/07)
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- Stereoselective divergent synthesis of four diastereomers of pachastrissamine (Jaspine B)
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Figure presented A divergent short synthesis of four diastereomers of pachastrissamine was achieved. Natural pachastrissamine was synthesized through bis-tosylation of the common intermediate and cyclization. 2-epi- Pachastrissamine was obtained by monotosylation and spontaneous cyclization of d-ribo-phytosphingosine derivative. By use of regio- and stereospecific ring-opening reaction of the orthoester assisted by a Boc group as a key step, 3-epi- and 2,3-epi-pachastrissamines were synthesized. The three stereogenic centers of all the diastereomers were constructed by using Garners aldehyde as the sole chiral source.
- Yoshimitsu, Yuji,Inuki, Shinsuke,Oishi, Shinya,Fujii, Nobutaka,Ohno, Hiroaki
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supporting information; experimental part
p. 3843 - 3846
(2010/09/03)
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- α-S-GalCer: Synthesis and evaluation for iNKT cell stimulation
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The synthesis and evaluation for iNKT stimulation of α-S-galactosylceramide is reported. Prepared by alkylation of a galactosylthiol, this analog of the potent immunostimulatory agent, KRN7000, did not stimulate iNKT cells either in vitro or in vivo.
- Blauvelt, Marisa L.,Khalili, Maryam,Jaung, Weonjoo,Paulsen, Janet,Anderson, Amy C.,Brian Wilson,Howell, Amy R.
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supporting information; experimental part
p. 6374 - 6376
(2009/09/30)
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- Dihydroxylation of 2-vinylaziridine: Efficient synthesis of D-ribo-phytosphingosine
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An efficient and highly stereoselective synthesis of D-ribo-(2S,3S,4R)- phytosphingosine was accomplished in 62% overall yield starting from commercially available (2S)-hydroxymethylaziridine via osmium-catalyzed asymmetric dihydroxylation as a key step. The Royal Society of Chemistry.
- Yoon, Hyo Jae,Kim, Yong-Woo,Lee, Baeck Kyoung,Lee, Won Koo,Kim, Yongeun,Ha, Hyun-Joon
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- Synthesis and preliminary antifungal evaluation of a library of phytosphingolipid analogues
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A library of 64 phytosphingolipid analogues resulting from the systematic variation of the C1, C3, C4, and the N-acyl moiety of phytosphingosine (PHS) has been prepared from common scaffolds derived from the chiral pool and Sharpless asymmetric dihydroxylation reactions. Library members have been evaluated as growth inhibitors of the yeast Saccaromyces cerevisiae. In addition, 1-amino-N-pivaloyl PHS analogues were also tested as IPC synthase inhibitors, in comparison with the natural product khafrefungin. The Royal Society of Chemistry 2007.
- Mormeneo, David,Casas, Josefina,Llebaria, Amadeu,Delgado, Antonio
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p. 3769 - 3777
(2008/10/09)
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- An efficient synthesis of the natural tetrahyclrofuran pachastrissamine starting from D-ribo-phytosphingosine
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The natural product pachastrissamine, an anhydrophytosphingosine derivative isolated from various sponges and endowed with cytotoxic activity against several human carcinoma cell lines, was synthesized in three steps and with 72% overall yield from D-ribo
- Van Tien Berg, Richard J. B. H. N.,Boltje, Thomas J.,Verhagen, Carlo P.,Litjens, Remy E. J. N.,Van Der Marel, Gijsbert A.,Overkleeft, Herman S.
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p. 836 - 839
(2007/10/03)
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- An efficient high-yield synthesis of D-ribo-phytosphingosine
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[4R-[4α(S*),5α]]-2,2-Dimethyl-4-(2-oxo-5-vinyl[1,3] dioxolan-4-yl)oxazolidine-3-carboxylic acid tert-butyl ester 5a, obtained in excellent yield and diastereoselectivity by the α-hydroxyallylation of the Garner aldehyde (4), is exploited in a novel high-yield synthesis of D-ribo-phytosphingosine (8), using microwave-enhanced cross metathesis as the key step in the chain elongation.
- Lombardo, Marco,Capdevila, Montse Guiteras,Pasi, Filippo,Trombini, Claudio
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p. 3303 - 3305
(2007/10/03)
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- An efficient synthesis of D-ribo- and L-lyxo-phytosphingosine from D-tartaric acid
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The preparations of D-ribo- and L-lyxo-phytosphingosines (1, 2) are described. Chelation-controlled addition of tetradecylmagnesium bromide to pentylidene-protected D-threitol aldehyde 6 afforded the key intermediate tetrol 7, providing the desired L-lyxo stereochemistry of phytosphingosine. Inversion at C4 of intermediate 7 provided the D-ribo stereochemistry.
- Lu, Xuequan,Bittman, Robert
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p. 3165 - 3168
(2007/10/03)
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- Novel synthetic C-glycolipids, their synthesis and use to treat infections, cancer and autoimmune diseases
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The invention is directed to novel compounds of formulae (I), (II) and (III): wherein X is O or NH; R3 is OH or a monosaccharide and R4 is hydrogen, or R3 is hydrogen and R4 is OH or a monosaccharide; R5 is hydrogen or a monosaccharide; and pharmaceutically acceptable salts or esters thereof. The invention is also directed to the use of the compounds both directly and as immune adjuvants for treating cancer, infectious diseases and autoimmune diseases. The invention is also directed to syntheses of the intermediates which can be used to make these novel compounds.
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(2010/02/14)
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- A process for the synthesis of sphingosine
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This invention relates to a method for the production of a sphingoid base according to formula comprising the steps of(1) dissolving a starting compound according to formula III or a salt thereof in a substantially inert solvent,(2) protecting the NH2 group with a NH2 protecting group,(3) activating C4 HR3' for an elimination reaction with C5HR4,(4) causing an elimination reaction to take place to form a double bond between the C4 and C5 carbon atom,(5) removing the NH2 protecting group.
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- Efficient synthesis of α-C-galactosyl ceramide immunostimulants: Use of ethylene-promoted olefin cross-metathesis
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(Chemical Equation Presented) Olefin cross-metathesis has been used to prepare α-C-galactosylceramide derivatives. The metathesis process merged vinyl and propenyl glycosides with vinyl derivatives of phytosphingosine. The use of ethylene enhanced the yie
- Chen, Guangwu,Schmieg, John,Tsuji, Moriya,Franck, Richard W.
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p. 4077 - 4080
(2007/10/03)
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- Process for the synthesis of sphingosine
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This invention relates to a method for the production of a sphingoid base according to formula comprising the steps of (1) dissolving a starting compound according to formula III or a salt thereof in a substantially inert solvent, (2) protecting the NHsu
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- A simple and low cost synthesis of D-erythro-sphingosine and D-erythro-azidosphingosine from D-ribo-phytosphingosine: Glycosphingolipid precursors
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D-erythro-Sphingosine (1) and D-erythro-2-azidosphingosine (2) are both prepared from commercially available and cheap D-ribo-phytosphingosine (3) in a yield of 58% and 70%, respectively. A key transformation in the synthesis of D-erythro-sphingosine (1) is the palladium catalyzed regiospecific reduction of the Z-enol triflate 9. A crucial step in the synthesis of azidosphingosine 2 comprises a regio- and stereoselective in situ trans-elimination of the 4-O-triflate of azidophytosphingosine 13.
- Van Den Berg, Richard J.B.H.N.,Korevaar, Cornelis G.N.,Van Der Marel, Gijsbert A.,Overkleeft, Herman S.,Van Boom, Jacques H.
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p. 8409 - 8412
(2007/10/03)
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- A short and efficient synthesis of phytosphingosines using asymmetric dihydroxylation
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A short synthesis of the phytosphingosine derivatives and their stereoisomers by using asymmetric dihydroxylation of the optically active olefins derived from L-serine is described.
- Imashiro, Ritsuo,Sakurai, Osamu,Yamashita, Toyoharu,Horikawa, Hiroshi
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p. 10657 - 10670
(2007/10/03)
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- Regio- and stereoselective incorporation of a13C nuclide into D-ribo-phytosphingosine via SmI2-mediated C-C formation with13C-labeled isocyanide
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Preparation of a 13C-labeled isocyanide and its application to the total synthesis of [2-13C]D-ribo-C18-phytosphingosine are described. The synthesis of the labeled phytosphingosine is based on the use of the isocyanide as a 13CH-NH2 precursor in the SmI2-mediated three-component coupling reaction, wherein regio- and stereoselective incorporation of a 13C nuclide in the carbon skeleton is achieved.
- Murakami, Masahiro,Ito, Hajime,Ito, Yoshihiko
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p. 185 - 186
(2007/10/03)
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