专利号:US-9884885-B2 优先权日:2009-05-18 标题:Synthesis of labile base protected-modified deoxy and modified ribo nucleosides, corresponding phosphoramidites and supports and their use in high purity oligonucleotide synthesis 发明人:SRIVASTAVA SURESH C; SRIVASTAVA NAVEEN P 权利人:SRIVASTAVA SURESH C; SRIVASTAVA NAVEEN P; CHEMGENES CORP 摘要:This invention relates to novel method of synthesis of RNA utilizing N-2-acetyl protected guanine as nucleoside base, nucleosides, succinates, phosphoramidites, corresponding solid supports that are suitable for oligo deoxy nucleosides and RNA oligonucleotide synthesis. Our discovery using N-acetyl protected guanine as nucleoside base protecting group, which is significantly faster base labile protecting group, yet significantly more stable than commonly utilized-2-isobutyryl guanosine is a novel approach to obtain highest purity oligonucleotides. This approach is designed to lead to very high purity and very clean oligonucleotide, after efficient removal of the protecting groups, including acetyl group from guanine and to produce high purity therapeutic grade DNA oligonucleotides, RNA oligonucleotides, diagnostic DNA, diagnostic RNA for microarray platform. The deprotection of acetyl protecting groups of the natural deoxy and ribonucleosides occurs under substantially reduced time in contact with mild deprotection conditions such as mild bases, secondary amines for removal of such groups under such conditions would allows synthesis of various DNA and RNA of highest purity for diagnostics and therapeutic application. This approach is designed to lead to high purity large scale therapeutic grade oligonucleotide chimeras which consist of fluoro sugar modification in conjunction with deoxy nucleosides, ribonucleosides, modified base and modified sugar nucleosides. This approach is further designed to use acetyl guanine protecting group when other bases are sensitive nucleoside, and for use in oligo peptide synthesis and for support bound oligo nucleotides.
专利号:US-8981076-B2 优先权日:2008-11-29 标 题 :Synthesis of N-FMOC protected deoxy nucleosides, ribo nucleosides, modified deoxy and ribo nucleosides, and phosphoramidites, and their use in oligonucleotide synthesis 发明人:SRIVASTAVA SURESH C; SRIVASTAVA NAVEEN P 权利人:SRIVASTAVA SURESH C; SRIVASTAVA NAVEEN P; CHEMGENES CORP 摘要:This invention relates to synthesis of novel -N-FMOC protected nucleosides, succinates, phosphoramidites, corresponding solid supports that are suitable for oligo deoxy nucleosides and RNA oligonucleotide synthesis. Our discovery using N-FMOC as nucleoside base protecting group, which is highly base labile protecting group is a novel approach to obtain highest purity oligonucleotides. This approach is designed to lead to very high purity and very clean oligonucleotide, after efficient removal of the protecting groups and to produce high purity therapeutic grade DNA oligonucleotides, RNA oligonucleotides, diagnostic DNA, diagnostic RNA for microarray platform. The deprotection of FMOC protecting groups of the natural deoxy and ribonucleosides occurs under very mild deprotection conditions such as mild bases, secondary and tertiary amines for removal of such groups under such conditions would allows synthesis of various DNA and RNA of highest purity for diagnostics and therapeutic application. This approach is further designed to use FMOC protecting group on various base sensitive nucleoside, and for use in oligo peptide synthesis and for support bound oligo nucleotides. DNA oligonucleotides containing 3′-end dA at the 3′-terminal will be produced using the FMOC-dA-supports would lead to much reduced M−1 deletion sequences, and thereby high purity.
专利号:US-12383499-B2 优先权日:2018-01-01 标题:Scale up synthesis of silicasome nanocarriers 发明人:NEL ANDRE E; MENG HUAN; LIU XIANGSHENG 权利人:UNIV CALIFORNIA 摘要:In order to facilitate the approval and commercialization of silicasome drug delivery systems (e.g. irinotecan silicasomes) it is necessary to scale up synthesis of the drug-loaded silicasomes. In this regard, it was discovered that the synthesis protocols used for laboratory synthesis of drug-loaded silicasomes (e.g., 500 mg/batch) do not scale to large scale silicasome production, because the resulting products were too heterogeneous for use as pharmaceuticals. Accordingly, new methods are provided herein that effectively afford the large-scale production of mesoporous silica nanoparticles (MSNPs) and lipid bilayer coated MSNPs (silicasomes).
专利号:US-10167308-B2 优先权日:2013-09-14 标题:Highly efficient synthesis of long RNA using reverse direction approach 发明人:SRIVASTAVA SURESH C; SRIVASTAVA NAVEEN P 权利人:CHEMGENES CORP 摘要:The present invention relates to novel process of reverse 5′→3′ directed synthesis of RNA oligomers in the range of about 100-mer to about 200-mer has been developed and disclosed. Using that method demonstrated high quality RNA synthesis with coupling efficiency approaching 99%.
专利号:US-2003162992-A1 优先权日:2001-12-14 标 题 :Preparation of intermediates useful in the synthesis of antiviral nucleosides 发明人:WATANABE KYOICHI A; DU JINFA 摘要:The present invention is an efficient process for the manufacture of α-acyloxyacetaldehyde, a key intermediate in the synthesis of 1,3-oxathiolane and 1,3-dioxolane nucleosides.
专利号:US-6005097-A 优先权日:1996-06-14 标题 :Processes for high-yield diastereoselective synthesis of dideoxynucleosides 发明人:CHEN SHU-HUI; LI XIUYAN 权利人:VION PHARMACEUTICALS INC 摘要:The present invention relates to methods for substantially enhancing the stereoselective synthesis of β-anomeric nucleoside analogs. In methods according to the present invention, the introduction of a phenylseleno group onto a blocked lactone sugar precursor may be selected so that the desirable phenylseleno substituent is introduced on the side of the blocked lactone away from the blocking group. This stereospecific introduction of the phenylseleno group in sugar precursor allows the synthesis of nucleoside analogs and in particular, 2',3',-dideoxy- and 2',3'-dideoxy-2',3'-didehydronucleoside analogs in very high yield. In certain preferred embodiments, the preferred phenylseleno blocked lactone is obtained in an amount representing approximately 90% or more of the total amount of the stereoisomers obtained. In even more preferred embodiments, the amount of the preferred stereoisomer is at least 95%, even more preferably at least about 97% of the total amount of phenylseleno blocked lactone produced.
1: Yao ZW, Lu X, Shen C, Lin DF. Comparison of flucytosine and fluconazole combined with amphotericin B for the treatment of HIV-associated cryptococcal meningitis: a systematic review and meta-analysis. Eur J Clin Microbiol Infect Dis. 2014 Aug;33(8):1339-44. doi: 10.1007/s10096-014-2074-2. Epub 2014 Feb 20. Review. doi: 10.1093/jac/dkt221. Epub 2013 Jun 20. Review. 3: Patel R. Antifungal agents. Part I. Amphotericin B preparations and flucytosine. Mayo Clin Proc. 1998 Dec;73(12):1205-25. Review. Review. Review. Review. Review. Review. Review. German. Review. Review. Review. Review.
合成参考文献
参考文献:10.1007/s10266-009-0118-3 摘要:Niimi M, Firth NA, Cannon RD. Antifungal drug resistance of oral fungi. Odontology. 2010 Feb;98(1):15–25. doi: 10.1007/s10266-009-0118-3. 参考文献:10.1001/archoto.2009.214 摘要:Price DL, Lin SF, Han Z, Simpson G, Coffin RS, Wong J, Li S, Fong Y, Wong RJ. Oncolysis using herpes simplex virus type 1 engineered to express cytosine deaminase and a fusogenic glycoprotein for head and neck squamous cell carcinoma. Arch Otolaryngol Head Neck Surg. 2010 Feb;136(2):151–8. 参考文献:10.1007/s00280-010-1262-8 摘要:Naito S, Tsukamoto T, Usami M, Fujimoto H, Akaza H. An early phase II trial of S-1 in Japanese patients with cytokine-refractory metastatic renal cell carcinoma. Cancer Chemother Pharmacol. 2010 Nov;66(6):1065–70. doi: 10.1007/s00280-010-1262-8. 参考文献:10.1186/1471-2180-11-163 摘要:Heisig M, Frentzen A, Bergmann B, Galmbacher K, Gentschev I, Hotz C, Schoen C, Stritzker J, Fensterle J, Rapp UR, Goebel W. Specific antibody-receptor interactions trigger InlAB-independent uptake of listeria monocytogenes into tumor cell lines. BMC Microbiology. 2011 Jul 11;11(1):163. doi: 10.1186/1471-2180-11-163. 参考文献:10.1007/s00436-011-2515-0 摘要:Polat ZA, Obwaller A, Vural A, Walochnik J. Efficacy of miltefosine for topical treatment of Acanthamoeba keratitis in Syrian hamsters. Parasitol Res. 2012 Feb;110(2):515–20. doi: 10.1007/s00436-011-2515-0.