CCCC.—The synthesis of four amino-3-hydroxy-1 : 4-benzisooxazines

Newbery, George; Phillips, Montague Alexandra

doi:10.1039/jr9280003046

Cited by 10 publications

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“…4 Therefore, active studies for the synthetic development of benzoxazine derivatives have been carried out. [5][6][7] We have also been interested in the new synthetic study of such benzoxazine derivatives. As part of our program aimed at developing new methods for the preparation of biologically active heterocycles, 8 we would like to report one-pot synthesis of 3-aryl-2H-benzo [1,4]oxazines by the condensation of o-aminophenols and 2-bromo-1-aryl-ethanones using HClO 4 -SiO 2 as an efficient catalyst in good yields (Scheme 1).…”

Section: Introductionmentioning

confidence: 99%

HClO₄‐SiO₂: An Efficient and Useful Catalyst for the Synthesis of 3‐Aryl‐2H‐benzo[1,4]oxazine

2009

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Section: Introductionmentioning

confidence: 99%

HClO₄‐SiO₂: An Efficient and Useful Catalyst for the Synthesis of 3‐Aryl‐2H‐benzo[1,4]oxazine

2009

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“…2 Prior work on the aromatic substitution of (2H)-1,4benzoxazin-3(4H)-one has shown that monobromination gave firstly the 6-bromo and then the 6,7-dibromo derivative. 3 In contrast to this, nitration has been reported 4,5 to give the 6-nitro and then the 6,8-dinitro compound. Nitration of the 6-chloro compound gave the 6-chloro-7-nitro-1,4-(2H)-benzoxazin-3(4H)-one.…”

mentioning

confidence: 94%

The Bromination and Nitration of Some (2H)-1, 4-Benzoxazin-3(4H)-Ones

Hanson¹,

Richards²,

Rozas³

2003

Journal of Chemical Research

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The (2H)-1,4-benzoxazin-3(4H)-one ring system is present in a number of biologically active natural products including the phytoalexins of grasses, which are formed in vitro by the hydroxylation of (2H)-1,4-benzoxazin-3(4H)-one. 1 In connection with the preparation of potential anti-fungal agents modelled on these compounds, we had occasion to examine the aromatic substitution of some (2H)-1,4-benzoxazin-3(4H)ones. 2 Prior work on the aromatic substitution of (2H)-1,4benzoxazin-3(4H)-one has shown that monobromination gave firstly the 6-bromo and then the 6,7-dibromo derivative. 3 In contrast to this, nitration has been reported 4,5 to give the 6-nitro and then the 6,8-dinitro compound. Nitration of the 6-chloro compound gave the 6-chloro-7-nitro-1,4-(2H)-benzoxazin-3(4H)-one. 6 We have confirmed the orientation of these substitutions by nuclear Overhauser effect (nOe) enhancements based on irradiation of the N-H signal. This led to the identification of the H-5 signal. We have then extended the study of the aromatic substitution under different conditions in the context of preparing polysubstituted derivatives.Bromination of (2H)-1,4-benzoxazin-3(4H)-one 7 (4, Scheme 1) with bromine in glacial acetic acid gave firstly the 6-bromo 3 and then the 6,7-dibromo compound 1 whilst bromine in chloroform gave mainly the 7-bromo derivative 6. Bromination of the 6-chloro-and 6-methyl-(2H)-1,4-benzoxazin-3(4H)-ones and (2H)-1,4-benzothiazin-3(4H)-ones gave the 7-bromo compounds. Nitration of (2H)-1,4-benzoxazin-3(4H)-one 4 with a sulfuric acid:nitric acid mixture gave the 6-nitro 5 and then the 6,8-dinitro compound 2 whilst nitrosation : nitration with sodium nitrite:fuming nitric acid gave mainly the 7-nitro compound 7. 6-Chloro-(2H)-1,4-benzoxazin-3(4H)-one gave the 7-nitro compound.The orientation of bromination of these (2H)-benzoxazin-3 (4H)-ones parallels that of the substitution reactions of N-acetyl-o-anisidine including dibromination which gives 4, 5-dibromo-2-methoxyacetanilide. 9 However, dinitration gives 4,5-dinitro-2-methoxyacetanilide 10 and the 4,6-dinitro compound is only obtained on further nitration of 4-nitro-2methoxy-N-toluene-p-sulfonylaniline. 11 Techniques used: NMR spectroscopy, nOe enhancements References: 11

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“…After the crude residue was applied onto a silica column (150 g of SiO 2 , 4 ϫ 24 cm), RO-09-3143 was eluted with 700 ml of CH 2 Cl 2 /acetone (20:1), which yielded 1.25 g of RO-09-3143 (with an overall yield of 69%). 8-Amino-4H-benz [1,4]oxazin-3-one was synthesized according to the method of Newbery and Phillips (15).…”

Section: Synthesis Of Ro-09-3143mentioning

confidence: 99%

Identification of a Novel Inhibitor Specific to the Fungal Chitin Synthase

Sudoh¹,

Yamazaki²,

Masubuchi³

et al. 2000

Journal of Biological Chemistry

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As in Saccharomyces cerevisiae, the pathogenic fungus Candida albicans harbors three chitin synthases called CaChs1p, CaChs2p, and CaChs3p, which are structurally and functionally analogous to the S. cerevisiae ScChs2p, ScChs1p, and ScChs3p, respectively. In S. cerevisiae, ScCHS1, ScCHS2, and ScCHS3 are all nonessential genes; only the simultaneous disruption of ScCHS2 and ScCHS3 is lethal. The fact that a null mutation of the CaCHS1 is impossible, however, implies that CaCHS1 is required for the viability of C. albicans. To gain more insight into the physiological importance of CaCHS1, we identified and characterized a novel inhibitor that was highly specific to CaChs1p. RO-09-3143 inhibited CaChs1p with a K i value of 0.55 nM in a manner that was non-competitive to the substrate UDP-N-acetylglucosamine. RO-09-3143 also hampered the growth of the C. albicans cells with an MIC 50 value of 0.27 M. In the presence of RO-09-3143, the C. albicans cells failed to form septa and displayed an aberrant morphology, confirming the involvement of the C. albicans Chs1p in septum formation. Although the effect of RO-09-3143 on the wild-type C. albicans was fungistatic, it caused cell death in the cachs2⌬ null mutants but not in the cachs3⌬ null mutants. Thus, it appears that in C. albicans, inhibition of CaChs1p causes cell growth arrest, but simultaneous inhibition of CaChs1p and CaChs2p is lethal.Candida albicans is an opportunistic pathogen and is one of the most common pathogens in humans. In healthy individuals, it remains in the oral cavity, gastrointestinal tract, and genitalia; however, it colonizes and invades various tissues and organs and causes systemic fungal infections in neutropenic individuals, such as AIDS patients and those undergoing cancer chemotherapy or immunomodulation therapy for organ transplantation. Polyenes and azoles are used to treat systemic Candida infections, but the adverse effects of polyenes and the emergence of Candida strains resistant to azole compounds make the treatment of patients with systemic mycosis difficult (1).Chitin is one of the essential components of the fungal cell wall. As in Saccharomyces cerevisiae, C. albicans harbors three chitin synthases, which are encoded by distinct genes called CaCHS1 (2), CaCHS2 (3), and CaCHS3 (4, 5). According to the sequences and functional analogies, CaChs1p, CaChs2p, and CaChs3p are considered to correspond to S. cerevisiae Chs2p (ScChs2p), Chs1p (ScChs1p), and Chs3p (ScChs3p), respectively (2-13). CaChs2p is the most abundant protein among the three C. albicans chitin synthases (13), but it is not essential for viability, hyphal growth, or virulence (12, 14). CaChs1p and CaChs3p are required for septum formation and for a large part of the cell wall synthesis, respectively (11, 14). The expression of CaCHS2 and CaCHS3 is up-regulated during the morphogenetic transition from yeast to hyphae (3, 4, 13), whereas the expression of CaCHS1 remains low in both the yeast and hyphal forms (3). Although the cachs3⌬ null mutants retained the ability ...

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CCCC.—The synthesis of four amino-3-hydroxy-1 : 4-benzisooxazines

Cited by 10 publications

References 0 publications

HClO₄‐SiO₂: An Efficient and Useful Catalyst for the Synthesis of 3‐Aryl‐2H‐benzo[1,4]oxazine

HClO₄‐SiO₂: An Efficient and Useful Catalyst for the Synthesis of 3‐Aryl‐2H‐benzo[1,4]oxazine

The Bromination and Nitration of Some (2H)-1, 4-Benzoxazin-3(4H)-Ones

Identification of a Novel Inhibitor Specific to the Fungal Chitin Synthase

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CCCC.—The synthesis of four amino-3-hydroxy-1 : 4-benzisooxazines

Cited by 10 publications

References 0 publications

HClO4‐SiO2: An Efficient and Useful Catalyst for the Synthesis of 3‐Aryl‐2H‐benzo[1,4]oxazine

HClO4‐SiO2: An Efficient and Useful Catalyst for the Synthesis of 3‐Aryl‐2H‐benzo[1,4]oxazine

The Bromination and Nitration of Some (2H)-1, 4-Benzoxazin-3(4H)-Ones

Identification of a Novel Inhibitor Specific to the Fungal Chitin Synthase

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HClO₄‐SiO₂: An Efficient and Useful Catalyst for the Synthesis of 3‐Aryl‐2H‐benzo[1,4]oxazine

HClO₄‐SiO₂: An Efficient and Useful Catalyst for the Synthesis of 3‐Aryl‐2H‐benzo[1,4]oxazine