Triazole antifungals. II. Synthesis and antifungal activities of 3-acyl-4-methyloxazolidine derivatives.

Konosu, Toshiyuki; Tajima, Yawara; Takeda, Noriko; Miyaoka, Takeo; Kasahara, Mayumi; Yasuda, Hiroshi; Oida, Sadao

doi:10.1248/cpb.38.2476

Cited by 32 publications

(8 citation statements)

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“…The synthetic utility of the allylic hydroxylation process was also demonstrated by the elaboration of tertiary 1,2-diol 2k into the corresponding triol 10 (Scheme ), which is a key intermediate for the preparation of triazole antifungal agents, such as Genaconazole, Ravuconazole, and Albaconazole. The reaction of 1k with water in 6 mmol scale using ( S )- L4 as a ligand proceeded smoothly to afford ( R )- 2k in 92% yield (1.1 g) with 94% ee.…”

Section: Resultssupporting

confidence: 58%

“…Epoxidation of 2k with 3-chloroperoxybenzoinc acid ( m -CPBA) under −10 °C gave epoxide 9 in 84% yield with a 7:1 diastereomeric ratio, and subsequent reduction of the epoxide by the treatment of lithium aluminum hydride afforded triol 10 in 85% yield. The absolute configuration of triol 10 was confirmed by the comparison of 1 H NMR data with those reported …”

Section: Resultsmentioning

confidence: 99%

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Enantioselective Construction of Tertiary C–O Bond via Allylic Substitution of Vinylethylene Carbonates with Water and Alcohols

Khan

et al. 2017

J. Am. Chem. Soc.

150

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An efficient method for the enantioselective construction of tertiary C-O bond via asymmetric allylic substitution of racemic vinylethylene carbonates with water and alcohols has been developed. Under the cooperative catalysis system of an in situ generated chiral palladium complex and boron reagent in mild conditions, the process allowed rapid access to valuable tertiary alcohols and ethers in high yields with complete regioselectivities and high enantioselectivities. This protocol represented the first example of direct enantioselective formation of a tertiary C-O bond with water as an oxygen donor. The synthetic utilities of the process have been demonstrated by the elaboration of the products into key intermediates of biologically relevant agents, and chiral tertiary cyclic ethers could also be provided through the sequential reactions of the allylic etherification and ring-closing metathesis.

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Section: Resultssupporting

confidence: 58%

Section: Resultsmentioning

confidence: 99%

Enantioselective Construction of Tertiary C–O Bond via Allylic Substitution of Vinylethylene Carbonates with Water and Alcohols

Khan

et al. 2017

J. Am. Chem. Soc.

150

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“…The triazole anion formed by reaction with NaH in DMF was introduced, opening the epoxide to yield the monoprotected diol 9 . After the THP group was cleaved by pyridinium p -toluenesulfonate, the diol 10 was obtained as a orange solid. ,,,,, Recrystallization from diethyl ether reduced impurities and increased the de to >99% . The purging of impurities and diastereomers which had accumulated over six telescoped steps largely accounted for the low overall yields (38−41%).…”

Section: Resultsmentioning

confidence: 99%

“…In addition to communicating an informative description of the scale-up of 1 from the laboratory to the plant, intermediates 8 , 10 , and 14 are precursors of other antifungal agents. ,,− This description of their large-scale preparations should facilitate future syntheses of these antimycotic agents and their related analogues . We also describe the use of FTIR spectroscopy for the control of the initiation, preparation, and reaction of a reactive Grignard reagent at pilot-plant scale …”

Section: Introductionmentioning

confidence: 99%

The Process Development of Ravuconazole: An Efficient Multikilogram Scale Preparation of an Antifungal Agent

Pesti

Chen

Spangler

et al. 2009

Org. Process Res. Dev.

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The development of a safe, robust process for the preparation of ravuconazole (1), an antifungal agent, is described. The discovery and development of procedures enabling the efficient synthesis of multikilogram quantities of 1 and the process demonstration through plant scale preparations are presented. A controlled means to prepare a Grignard reagent and utilization of Fourier Transform Infrared spectroscopy (FTIR) monitoring to safely conduct the reaction is featured.

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“…Synthesis of target compounds: The general synthetic methodology for the preparation of title compounds is outlined in Scheme-I. The key intermediate 1 was synthesized by the reported procedure 11,12 , the triazolone-containing side chains were prepared via four steps. Various substituted benzoic acid 1-10a were converted to methyl benzoate 1-10b by reacting with methanol, followed by treating with hydrazine hydrate to give benzohydrazide 1-10c.…”

mentioning

confidence: 99%

Synthesis and Evaluation of Some Substituted Heterocyclic Fluconazole Analogues as Antifungal Agents

Wang¹,

Zhang²,

Jin³

et al. 2014

Asian J. Chem.

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During the past few decades, fungal infections are the commonly prevalent diseases from which a large proportion of the human population suffers 1-5. The increased emergence of both the superficial and systemic fungal infections has led to the massive increase in the rate of mortality, especially in the immuno-compromised individuals, those suffering from tuberculosis, cancer or AIDS 6,7. In clinic, azoles, especially triazole antifungal agents, were used most widely and efficiently. For example, fluconazole, voriconazole and itraconazole, presently play an important role in the treatment of fungal infections. However, their clinical use has been limited by the emergence of drug resistance, high risk of toxicity, insufficiencies in their antifungal activity and undesirable side effects 8-10. Hence, there is still a need to develop the safe and efficient chemotherapeutic agents with potent broad spectrum antifungal activities 10. EXPERIMENTAL Analytical TLC was carried out on Silica Gel 60 F254 plates (E. Merck) with detection by fluorescence and/or by charring with 10 % (v/v) H2SO4 in EtOH. Column chromatograph was performed on silica gel (200-300 mesh, Qindao Ocean Chemical Co., China). All chemicals and solvents were purchased from commercial sources unless specified otherwise. 1 H and 13 C NMR spectra were recorded in CDCl3, using

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Triazole antifungals. II. Synthesis and antifungal activities of 3-acyl-4-methyloxazolidine derivatives.

Cited by 32 publications

References 0 publications

Enantioselective Construction of Tertiary C–O Bond via Allylic Substitution of Vinylethylene Carbonates with Water and Alcohols

Enantioselective Construction of Tertiary C–O Bond via Allylic Substitution of Vinylethylene Carbonates with Water and Alcohols

The Process Development of Ravuconazole: An Efficient Multikilogram Scale Preparation of an Antifungal Agent

Synthesis and Evaluation of Some Substituted Heterocyclic Fluconazole Analogues as Antifungal Agents

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