The preparation of N-carboxyanhydrides of α-amino acids using bis(trichloromethyl)carbonate
TL;DR: In this article, a synthesis of NCA's of α-amino acids using bis(trichloromethyl) carbonate has been reported; the triphosgene is used to supply phosgenes in situ in stoichiometric amounts; it is particularly effective for preparing NCA of amino acids with long, aliphatic side chains.
About: This article is published in Tetrahedron Letters.The article was published on 1988-01-01. It has received 548 citations till now. The article focuses on the topics: Triphosgene & Dicarboxylic acid.
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Journal Article•
TL;DR: CDDP/m could be a promising formulation of CDDP for the targeted therapy of solid tumors, according to the passive targeting manner, and its utility as a tumor-targeted drug delivery system was investigated.
Abstract: Polymeric micelles incorporating cisplatin (CDDP) were prepared through the polymer-metal complex formation between CDDP and poly(ethylene glycol)-poly(glutamic acid) block copolymers, and their utility as a tumor-targeted drug delivery system was investigated. CDDP-incorporated micelles (CDDP/m) had a size of 28 nm with remarkably narrow distribution. CDDP/m were very stable in distilled water even in long-time storage, but exhibited a sustained drug release accompanied with the decay of the carrier itself in physiological saline. These micelles showed remarkably prolonged blood circulation and effectively accumulated in solid tumors (Lewis lung carcinoma cells) according to the passive targeting manner (20-fold higher than free CDDP). Reduced accumulation of the micelles in normal organs provided high selectivity to the tumor. In vivo antitumor activity assay demonstrated that both free CDDP and the CDDP/m had significant antitumor activity in C 26-bearing mice compared with nontreatment (P < 0.05 for free CDDP; P < 0.01 for CDDP/m), but complete tumor regression was observed only for the treatment with CDDP/m. Four of 10 mice treated with CDDP/m (4 mg/kg; five times administration at 2-day intervals) showed complete tumor regression with no significant body weight loss, whereas free CDDP treatment at the same drug dose and regime resulted in tumor survivals and approximately 20% of body weight loss. These data suggest that CDDP/m could be a promising formulation of CDDP for the targeted therapy of solid tumors.
593 citations
Cites methods from "The preparation of N-carboxyanhydri..."
...was synthesized by the Fuchs-Farthing method using triphosgene (41)....
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Patent•
TL;DR: Particles incorporating a surfactant and a hydrophilic or hydrophobic complex of a positively or negatively charged therapeutic agent and a charged molecule of opposite charge for drug delivery to the pulmonary system, and methods for their synthesis and administration are provided as discussed by the authors.
Abstract: Particles incorporating a surfactant and/or a hydrophilic or hydrophobic complex of a positively or negatively charged therapeutic agent and a charged molecule of opposite charge for drug delivery to the pulmonary system, and methods for their synthesis and administration are provided. In a preferred embodiment, the particles are made of a biodegradable material and have a tap density less than 0.4 g/cm3 and a mass mean diameter between 5 νm and 30 νm, which together yield an aerodynamic diameter of the particles of between approximately one and three microns. The particles may be formed of biodegradable materials such as biodegradable polymers. For example, the particles may be formed of poly(lactic acid) or poly(glycolic acid) or copolymers thereof. Alternatively, the particles may be formed solely of a therapeutic or diagnostic agent and a surfactant. Surfactants can be incorporated on the particule surface for example by coating the particle after particle formation, or by incorporating the surfactant in the material forming the particle prior to formation of the particle. Exemplary surfactants include phosphoglycerides such as dipalmitoyl phosphatidylcholine (DPPC). The particles can be effectively aerosolized for administration to the respiratory tract to permit systemic or local delivery of wide a variety of therapeutic agents. Formation of complexes of positively or negatively charged therapeutic agents with molecules of opposite charge can allow control of the release rate of the agents into the blood stream following administration.
577 citations
Patent•
23 May 1997
TL;DR: Improved aerodynamically light particles for delivery to the pulmonary system, and methods for their preparation and administration are provided in this paper, where the particles are made of a biodegradable material and have a tap density less than 0.4 g/cm3 and a mass mean diameter between 5 µm and 30 µm.
Abstract: Improved aerodynamically light particles for delivery to the pulmonary system, and methods for their preparation and administration are provided. In a preferred embodiment, the aerodynamically light particles are made of a biodegradable material and have a tap density less than 0.4 g/cm3 and a mass mean diameter between 5 µm and 30 µm. The particles may be formed of biodegradable materials such as biodegradable polymers. For example, the particles may be formed of a functionalized polyester graft copolymer consisting of a linear .alpha.-hydroxy-acid polyester backbone having at least one amino acid group incorporated therein and at least one poly(amino acid) side chain extending from an amino acid group in the polyester backbone. In one embodiment, aerodynamically light particles having a large mean diameter for example greater than 5 µm, can be used for enhanced delivery of a therapeutic or diagnostic agent to the alveolar region of the lung. The aerodynamically light particles optionally can incorporate a therapeutic or diagnostic agent, and may be effectively aerosolized for administration to the respiratory tract to permit systemic or local delivery of wide variety of incrorporated agents.
528 citations
Patent•
16 Jan 1997TL;DR: Aerodynamically light particles incorporating a surfactant on the surface thereof for drug delivery to the pulmonary system, and methods for their synthesis and administration are provided in this article, where the particles are made of a biodegradable material and have a tap density less than 0.4 g/cm 3 and a mass mean diameter between 5 μm and 30 μm.
Abstract: Aerodynamically light particles incorporating a surfactant on the surface thereof for drug delivery to the pulmonary system, and methods for their synthesis and administration are provided. In a preferred embodiment, the aerodynamically light particles are made of a biodegradable material and have a tap density less than 0.4 g/cm 3 and a mass mean diameter between 5 μm and 30 μm. The particles may be formed of biodegradable materials such as biodegradable polymers. For example, the particles may be formed of poly(lactic acid) or poly(glycolic acid) or copolymers thereof. Alternatively, the particles may be formed solely of the drug or diagnostic agent and a surfactant. Surfactants can be incorporated on the particle surface for example by coating the particle after particle formation, or by incorporating the surfactant in the material forming the particle prior to formation of the particle. Exemplary surfactants include phosphoglycerides such as L-α-phosphatidylcholine dipalmitoyl. The aerodynamically light particles incorporating a therapeutic or diagnostic agent and a surfactant may be effectively aerosolized for administration to the respiratory tract to permit systemic or local delivery of wide a variety of therapeutic agents.
493 citations
TL;DR: Polybutadiene-block-poly(L-glutamate) copolymers were made by anionic polymerization and subsequent ring-opening polymerization of N-carboxyanhydrides and were characterized by NMR, IR, SEC, and circular dichroism.
Abstract: Polybutadiene-block-poly(l-glutamate) copolymers were made by anionic polymerization and subsequent ring-opening polymerization of N-carboxyanhydrides and were characterized by NMR, IR, SEC, and circular dichroism. These polymers, when appropriately designed, form so-called “polymersomes” or “peptosomes”, vesicles composed of modified protein units. The size and structure of the vesicles are determined by dynamic light scattering, small-angle neutron scattering, and freeze-fracture electron microscopy. It is also shown that the size of the peptosomes does not depend on the pH; that is, the solvating peptide units can perform a helix−coil transition without serious changes of the vesicle morphology.
399 citations
References
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TL;DR: In this article, the vapor diffusion method was used to grow colorless crystals suitable for X-ray crystallography, which were obtained by slow evaporation of a chloroform solution of 8 at room temperature.
Abstract: 6 = 1.81 (m. 4H). 2.33 (m, 4H), 2.61 (m, 4H), 4.92 (s, 4H), 4.97 (bs, 4H), 4.99 ( s , 4H). 5.09 ( s , 4H), 6.99 (s, 2H); “C-NMR (CDCI?): 6=25.7, 43.2, 85.0, 85.3, 100.9, 110.2, 143.1, 144.2, 144.61. 6a: 6 (156 mg, 0.88 mmol) was heated under reflux (48 h, N2) with anthracene (50 mg, 0.28 mmol) in xylene (5 mL): yield of the crude product: after chromatography (SiO,/CHCI,-Et,O) 17 mg, I Io/i. Colorless crystals [m.p. >300”C), m/z (positive ion FABMS) 535 for (M+H)O] suitable for X-ray crystallography, were grown by the vapor diffusion method (CHCI,. CICHzCH,Cl-light petroleum). 8: Reaction (CH2Cl2, 9-10 kbar, 55-60”C. 200 h) of 7 (373 mg, 0.74 mmol) with 5 (156 mg, 0.74 mmol) yielded, after chromatography (SiO2/CHCl3MeOH), 8 [I05 mg, 20%, recrystallized from CHCI?, m.p. > 300”C, m/z (positive ion FABMS) 713 for (M+H)@: ‘H-NMR (CDCI,): 6=1.62 (m, 4H), 2.32(m,8H),2.63(m,8H),4.89(~,8H),5.08(~,4H),6.98(~,4H): “C-NMR (CDC13): 6=27.1, 44.2, 84.8, 86.6, I10.1, 144.6, 152.51, which was also obtained in very low yield (3.5%) by heating 6 under reflux (48 h, N2) in xylene. Single crystals, suitable for X-ray analysis, were obtained by slow evaporation of a chloroform solution of 8 at room temperature.
350 citations
TL;DR: Viscoelasticite, diffractometrie RX, calorimetrie differentielle et dispersion optique rotatoire de polymeres avec 5, 6, 8, 10, 12, 14, 16 and 18 atomes de carbone dans la chaine alkyle as discussed by the authors.
Abstract: Viscoelasticite, diffractometrie RX, calorimetrie differentielle et dispersion optique rotatoire de polymeres avec 5, 6, 8 ,10, 12, 14, 16 et 18 atomes de carbone dans la chaine alkyle
252 citations
143 citations
Book•
01 Jan 1983
96 citations
TL;DR: In this paper, the Darstellung von O-Benzyl-l-tyrosin gelingt leicht durch direkte Benzylierung des l-Tyrosin-Kupfer-Komplexes.
Abstract: Die Darstellung von O-Benzyl-l-tyrosin gelingt leicht durch direkte Benzylierung des l-Tyrosin-Kupfer-Komplexes. Die O-Maskierung ist mittels katalytisch erregten Wasserstoffs bzw. Natriums in flussigem Ammoniak glatt reversibel. Die Synthese von Glycyl-L-tyrosin, l-Tyrosyl-glycin, l-Leucyl-l-tyrosin und l-Cystinyl-bis-l-tyrosin unter Verwendung von O-Benzyl-L-tyrosin-methylester-hydrochlorid bzw. N-Carbobenzoxy-O-benzyl-L-tyrosin wird beschrieben.
78 citations