The structures of kidamycin derivatives: triacetylmethoxykidamycin bis(trimethylammonium) iodide and isokidamycin bis(<i>m</i>-bromobenzoate)

Furukawa, M.; Iitaka, Y.

doi:10.1107/s0567740880008564

Cited by 5 publications

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“…Like other pluramycins, 1 binds to DNA, leading to single strand cleavage . Kidamycin possesses an angular anthrapyranone tetracyclic core that is adorned with a β-angolosaminyl C -glycoside substituent at C(8) and an α- N , N -dimethylvancosaminyl C -glycoside group at C(10) . Kidamycin ( 1 ) is both light and acid sensitive and is easily transformed into isokidamycin ( 2 ) upon treatment with acid. , No doubt owing to their complex structures and labile functionality, none of the bis- C- arylglycoside antibiotics of the pluramycin family have succumbed to total synthesis.…”

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Total Synthesis of Isokidamycin

et al. 2010

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The synthesis of isokidamycin, which represents the first total synthesis of a bis-C-aryl glycoside natural product in the pluramycin family, has been completed. The synthesis features the use of a silicon tether as a disposable regiocontrol element in an intramolecular Diels-Alder reaction between a substituted naphthyne and a glycosyl furan and a subsequent O → C-glycoside rearrangement.Kidamycin (1) is a member of the pluramycin class of C-aryl glycoside antibiotics that was isolated from Streptomyces phaeoverticillatus and displays a broad range of antibacterial, antifungal and anticancer properties.i Like other pluramycins, 1 binds to DNA, leading to single strand cleavage.ii Kidamycin possesses an angular anthrapyranone tetracyclic core that is adorned with a β-angolosaminyl C-glycoside substituent at C(8) and an α-N,Ndimethylvancosaminyl C-glycoside group at C(10).iii Kidamycin (1) is both light and acid sensitive and is easily transformed into isokidamycin (2) upon treatment with acid.iiia , iv No doubt owing to their complex structures and labile functionality, none of the bis-Carylglycoside antibiotics of the pluramycin family have succumbed to total synthesis. Indeed, few have even dared to embark on such a challenging enterprise.v Several years ago we reported a unified strategy for preparing the four major classes of Caryl glycoside antibiotics.vi The approach relies on the ring-opening of glycosyl-substituted oxabicycles that are produced by the Diels-Alder reactions of substituted arynes with glycosyl furans. A significant feature of this novel entry to C-aryl glycosides is that it couples the introduction of the C-aryl glycoside moiety with the annelation of a new aromatic ring, thereby leading to a rapid increase in complexity. We subsequently applied this method to the syntheses of several C-aryl glycoside natural products.vii However, we wished to extend this methodology to the synthesis of a more complex member of the pluramycin family. We now report our efforts in this area that resulted in the total synthesis of isokidamycin (2), the first bis-C-arylglycoside antibiotic to be prepared by total synthesis.The essential elements of our approach to kidamycin are outlined in Figure 1. Given the known propensity for the N,N-dimethylvancosamine moiety at C(10) of 1 to suffer epimerization at the anomeric center to give 2, we favored the late stage introduction of this residue from the advanced intermediate 3 using the O→C-glycoside rearrangement that had been pioneered by Suzuki and had been shown to be applicable to the preparation of some α-C-aryl glycosides.viii We envisioned that anthrol 3 would be accessible from 4 by cleavage of the disposable silicon tether, ring-opening of the oxabicycle, and annelation of the NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript substituted pyranone ring. Intermediate 4 would then be formed by the pivotal intramolecular naphthyne-furan cycloaddition that would be initiated by reductive dehalogenation of 5, which would be assem...

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confidence: 99%