Polypeptide Antibiotics

KORZYBSKI, TADEUSZ; KOWSZYK-GINDIFER, ZUZANNA; KURYŁOWICZ, WŁODZIMIERZ

doi:10.1016/b978-1-4831-9802-6.50013-2

Cited by 5 publications

(6 citation statements)

References 71 publications

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“…Comparison of the crystalline synthetic (±)-anisomycin product with authentic natural (-)-anisomycin indicated total identity with 1 H NMR, 13 C NMR, IR, UV, and mass spectroscopy. In addition, in vitro tube-dilution biological testing against protozoa (Trichomonas vaginalis, T. foetus, and Entai'noeba hystolytica), yeasts (Candida albicans and Saccharomyces cerevisiae), and dermatophytes (Trichophyton mentogrophytes and Epidermophyton floccosum) indicated that the synthetic (±)-anisomycin possess half of the activity of the natural (-)-anisomycin.…”

Section: Synthesis From Pyrrolealdehydementioning

confidence: 98%

“…Anisomycin has a broad activity against certain pathogenic protozoa, strains of fungi [1][2][3][4][5][6][7][8][9][10][11][12]. It is effective in the treatment of amoebic dysentery and tricomonas vaginitis [13,14] and in plants as a fungicide [15]. Deacetyl anisomycin (2) has also been used as a fungicide in the eradication of bean mildew and for the inhibition of other pathogenic fungi in plants.…”

Section: Introductionmentioning

confidence: 99%

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New Developments in the Synthesis of Anisomycin and Its Analogues

Nemr

Ashry

2007

Heterocycles From Carbohydrate Precursors

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Section: Synthesis From Pyrrolealdehydementioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

New Developments in the Synthesis of Anisomycin and Its Analogues

Nemr

Ashry

2007

Heterocycles From Carbohydrate Precursors

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“…[1] Since its initial isolation 1 has aroused considerable interest due to its potent and specific antibiotic activity [2] against several microorganisms. It also inhibits the ribosomal peptide synthesis [3] and exhibits high antitumor activity.…”

Section: Introductionmentioning

confidence: 99%

Stereoselective Synthesis of (−)‐Deacetylanisomycin

Merino¹,

Franco²,

Lafuente³

et al. 2003

Eur J Org Chem

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“…5 Anisomycin possesses strong and selective activity against pathogenic protozoa and fungi and has been proved successful clinically in the treatment of amoebic dysentry and trichomonas vaginitis. 6 It has been shown to block ribosomal peptide synthesis. 6…”

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confidence: 99%

An Efficient Synthesis of (-)-Deacetylanisomycin Starting from d-Tyrosine

Chandrasekhar¹,

Ramachandar²,

Reddy³

2002

Synthesis

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The antibiotic (-)-deacetylanisomycin was synthesized starting from D-tyrosine using Sharpless asymmetric dihydroxylation as a key reaction.Anisomycin (1) is an antibiotic that has been isolated from fermentation broth filtrates of various species of Streptomyces. 2 X-ray crystallographic analysis 3 and chemical studies 4 reveal the structure and relative stereochemistry of anisomycin to be that depicted in structure 1 (Figure 1). The absolute stereochemistry was established as 2R,3S,4S by chemical correlation studies. 5 Anisomycin possesses strong and selective activity against pathogenic protozoa and fungi and has been proved successful clinically in the treatment of amoebic dysentry and trichomonas vaginitis. 6 It has been shown to block ribosomal peptide synthesis. 6 Figure 1The structure of Anisomycin (1) Although a few total synthesis of (-)-anisomycin have been reported 7 previously, the molecule still continues to attract the attention of synthetic organic chemists owing to its high biological profile. Our continued interest in the development of new and efficient synthetic routes to clinically significant amino compounds prompted us to investigate the total synthesis of (-)-deacetylanisomycin (2). 8 We wish to report herein the synthesis of 2 from D-tyrosine, which also constitutes a formal total synthesis of 1. It appeared to us that an expedient approach to 2 from Dtyrosine would involve a reaction sequence outlined as below (Scheme 1).Compound 4 was obtained in 70% yield from D-tyrosine by protecting the amino functionality using di-tert-butyl dicarbonate, followed by methylation of the acid and phenolic hydroxyl group with MeI/K 2 CO 3 . Reduction of ester 4 with lithium borohydride 9 furnished the alcohol 5 (72%). A Swern oxidation 10 followed by Wittig reaction with (ethoxycarbonylmethylene)triphenylphosphorane in CH 2 Cl 2 yielded the trans a,b-unsaturated ester 6 (73%). In order to avoid or minimize any possible racemization at the chiral centre, the aldehyde was used immediately without purification.Our strategy required that the olefination product 6 contained the desired trans geometry at the double bond for the subsequent creation of chiral diol via Sharpless asymmetric dihydroxylation. Upon reacting the N-Boc-protected g-amino-a,b-unsaturated ester 6 with the modified Sharpless asymmetric dihydroxylation conditions using AD-mix-a, 11 the expected (2R,3S,4R) configured ester 7 (60%) was obtained with high stereoselectivity (Scheme 2). This result has precedence. 12,13 N H HO OR MeO 1 R = COCH 3 2 R = H Scheme 1 HO NH 2 COOH MeO NHBoc COOMe MeO NHBoc MeO NHBoc OEt O 1) NaOH/Dioxane/H 2 O Boc 2 O 2) MeI/Acetone K 2 CO 3 Et 2 O/MeOH reflux 1) (COCl) 2 , DMSO DCM, Et 3 N, -78 °C 2) Ph 3 P=CHCOOEt CH 2 Cl 2 , r.t. 4 (70%) 5 (72%) 6 (73%) D-tyrosine LiBH 4 OH Downloaded by: Queen's University. Copyrighted material.

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Polypeptide Antibiotics

Cited by 5 publications

References 71 publications

New Developments in the Synthesis of Anisomycin and Its Analogues

New Developments in the Synthesis of Anisomycin and Its Analogues

Stereoselective Synthesis of (−)‐Deacetylanisomycin

An Efficient Synthesis of (-)-Deacetylanisomycin Starting from d-Tyrosine

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