Synthesis and Antifungal Activity of Rhodopeptin Analogues. 2. Modification of the West Amino Acid Moiety

Nakayama, Kiyoshi; Kawato, Haruko C.; Inagaki, Hiroaki; Nakajima, Riichiro; Kitamura, Akihiro; Someya, Kazuhiko; Ohta, Toshiharu

doi:10.1021/ol005630k

Cited by 87 publications

(42 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In recent years, a,a-difluoro-b-amino acids have received considerable interests owing to their synthetic application in the design of peptides, fluoroalkene dipeptide isosteres as well as a side chain of the docetaxel analogue [170][171][172][173][174][175]. Therefore, several methods for the asymmetric syntheses of a,a-difluoro-b-amino acid derivatives and/or dif luoro-b-lactams have been reported in the literature [176][177][178].…”

Section: Review | Kukhar Sorochinsky and Soloshonokmentioning

confidence: 99%

Practical Synthesis of Fluorine-Containing α- and β-Amino Acids: Recipes from Kiev, Ukraine

2009

View full text Add to dashboard Cite

Naturally occurring compounds containing a C-F bond are extremely rare; only a handful of fluorine-containing carboxylic acids have been described so far. By contrast, man-made fluorine-containing derivatives of all major classes of biologically important compounds are extremely promising medicinal targets used in the elucidation of biochemical, metabolic transformations and the development of new pharmaceuticals. Among the fluorine-containing derivatives of natural products, fluorinated analogs of amino acids are of particular interest and medicinal potential. This article presents a concise review of various synthetic methods, developed by the Kiev's school of bioorganic chemistry, for the preparation of fluorine-containing analogs of α- and β-amino acids, α-hydroxy acids, amines, as well as their phosphorus and sulfur-derived compounds, in enantiomerically pure form. One of the major methodological goals of the study was practicality, which is understood by us as stereochemical generality, operational convenience and synthetic affordance for each reaction step and isolation of the target products. The synthetic methods developed by our group can be roughly divided in two general categories: fluorine-adaptation of known synthetic approaches and discovery of new reactions. The former approach is most prominently represented by asymmetric homologation of nucleophilic glycine equivalents using fluorinated substrates via alkyl halide alkylations, aldol and Michael addition reactions. A plethora of discovered unexpected reaction outcomes, in particular stereochemical, are emphasized in this review and the particular role of fluorine, in altering the 'normal' reaction result, is explained. The latter direction is notably represented by the novel 1,3-proton shift reaction, a biomimetic reductive amination of fluorinated carbonyl compounds to the corresponding amines and amino acids, as well as the development of α-fluoroalkyl epoxides as true fluorinated synthons for generalized asymmetric synthesis of various biologically relevant compounds. Despite the highly anticipated potential of fluorine-containing amino compounds, their medicinal chemistry still remains underexplored. The major obstacle, in our opinion, is that these selectively fluorinated compounds are generally unavailable to the medicinal chemists for comprehensive, systematic study. We hope this review of synthetic methods will highlight and bring attention to particular types of fluorinated amino acids and related compounds readily available on a laboratory scale using methods developed by our group.

show abstract

Section: Review | Kukhar Sorochinsky and Soloshonokmentioning

confidence: 99%

Practical Synthesis of Fluorine-Containing α- and β-Amino Acids: Recipes from Kiev, Ukraine

2009

View full text Add to dashboard Cite

show abstract

“…As an example of this effect, the introduction of a gem ‐difluoromethylene group adjacent to a carbonyl group increases the propensity of the carbonyl group to adopt its tetrahedral hydrate form, which can increase the inhibitory activity of certain carbonyl compounds against proteases and esterases 7. As an example of both of these effects, Daiichi pharmaceuticals developed fluorinated rhodopeptin analogue 4 , which retained the antifungal activity but had a maximum tolerated dose (MTD) more than twice that of non‐fluorinated analogs of rhodopeptin 8. In addition, three fluorinated Docetaxel analogs of type 5 , also developed by Daiichi pharmaceuticals, were more potent than Paclitaxel in terms of both their GI 50 against the five cancer cell lines assayed and their inhibition (IC 50 ) of microtubule assembly 9…”

Section: Introductionmentioning

confidence: 99%

“…Often, the use of enantiopure starting materials or a chiral auxiliary is required to enable diastereoselective C–F bond‐forming reactions, as occurred in the synthesis of Sanofi–Aventis chemotherapeutic 1 and Daiichi Pharmaceuticals antibiotic 2 , respectively 10,11. It is also a common strategy to use non‐asymmetric bond‐forming reactions followed by a resolution of the resulting enantiomeric or diastereomeric mixture, as occurred in the Eli Lilly synthesis of AMPA potentiator 3 , and in the Daiichi Pharmaceuticals syntheses of 4 and 5 8,9,12…”

Section: Introductionmentioning

confidence: 99%

One‐Pot Preparation of Enantiopure Fluorinated β‐Amino Acid Precursors

Jones¹,

Appayee²,

Brenner‐Moyer³

2014

Eur J Org Chem

View full text Add to dashboard Cite

Keywords: Domino reactions / Fluorine / Amino acids / Organocatalysis / Synthetic methods Chiral β-fluoro amines and β,β-difluoro amines are common substructures in medicinal compounds. Industrial syntheses typically use enantiopure starting materials, chiral auxiliaries, or the resolution of enantiomeric or diastereomeric mixtures to install these functionalities in enantiopure form. With the goal of improving access to these substructures, we recently developed the first catalytic enantioselective olefin aminohalogenation reaction, which produced chiral β-fluoro amines in a single flask from achiral enal starting materials.

show abstract

“…For example, the CH 2 to CF 2 transposition in the b-amino acid fragment of Rhodopeptin, a natural cyclic tetrapeptide with antifungal activities, resulted in an improved toxicity profile. 4 The general methods for introducing fluorine atoms into organic molecules involve either direct fluorination (using fluorine gas, hydrogen fluoride, and fluorinating agents) or the use of fluorinated building blocks. 5 The use of fluorinated building blocks as a strategy for the construction of fluorinated organic molecules is becoming more popular.…”

mentioning

confidence: 99%

“…15 In 2000, Ohta described the ring-opening reaction of difluorinated b-lactam with sodium methoxide, followed by treatment with primary amine (glycine tert-butyl ester hydrochloride) to give aminolysis products. 4 In order to improve reaction efficiency and avoid the separation of the mixture of 3 and 4, herein, we tried to obtain difluorinated amide 5 by the reaction of cyclohexanamine with the mixture of 3 and 4 directly. To our delight, both of them could react with cyclohexanamine in methanol at room temperature to afford the same product 5 in almost quantitative yield.…”

mentioning

confidence: 99%

New gem-difluoromethylene-containing isocyanide as a useful building block for the synthesis of difluorinated pseudopeptides via Ugi reaction

Liu

Cao

Shen

et al. 2009

Tetrahedron Letters

View full text Add to dashboard Cite

Synthesis and Antifungal Activity of Rhodopeptin Analogues. 2. Modification of the West Amino Acid Moiety

Cited by 87 publications

References 15 publications

Practical Synthesis of Fluorine-Containing α- and β-Amino Acids: Recipes from Kiev, Ukraine

Practical Synthesis of Fluorine-Containing α- and β-Amino Acids: Recipes from Kiev, Ukraine

One‐Pot Preparation of Enantiopure Fluorinated β‐Amino Acid Precursors

New gem-difluoromethylene-containing isocyanide as a useful building block for the synthesis of difluorinated pseudopeptides via Ugi reaction

Contact Info

Product

Resources

About